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205 Cards in this Set
- Front
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1. Glucogenic amino acids
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Any amino acid that can be broken down and have its carbons or carbon skeletons used to synthesize glucose.
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2. Ketogenic amino acids
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Any amino acid whose carbons cannot be used to synthesize glucose.
Instead, their carbons or carbon skeletons can be converted directly to acetyl CoA or acetoacetate. |
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3. Which amino acids are essential to our diet?
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1. Histidine
2. Isoleucine 3. Leucine 4. Lysine 5. Methionine 6. Phenyalanine 7. Threonine 8. Tryptophan 9. Valine |
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4. Which amino acids are conditionally essential to our diet?
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1. Arginine
2. Cysteine 3. Glutamine 4. Glycine 5. Proline 6. Tyrosine |
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5. Which amino acids are considered nonessential?
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1. Alanine
2. Asparagine 3. Aspartate 4. Glutamate 5. Serine |
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6. Which five AAs are metabolized to α-KG and can ultimately be converted to glucose?
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1. Arginine
2. Histidine 3. Glutamate 4. Glutamine 5. Proline |
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7. Which four AAs are metabolized to Succinyl-CoA and can ultimately be converted to glucose?
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1. Isoleucine
2. Methionine 3. Threonine 4. Valine |
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8. Which AAs are ketogenic and glucogenic?
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1. Isoleucine
2. Methionine 3. Threonine 4. Valine |
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9. Coenzyme tetrahydrofolate
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Required in certain AA pathways to either accept or donate a one-carbon group. The carbon can be in various states of oxidation.
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10. Coenzyme tetrahydrobiopterin
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Required for ring hydroxylations.
The reactions involve molecular oxygen, and one atom of oxygen is incorporated into the product. Very important for the synthesis of tyrosine and neurotransmitters. |
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11. Which four AAs are synthesized from intermediates of glycolysis?
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1. Serine
2. Glycine 3. Cysteine 4. Alanine |
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12. Synthesis of serine
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In the biosynthesis of serine form glucose, 3-phosphoglycerate is first oxidized to a 2-keto compound (3-phosphohydroxypyruvate), which is then transaminated to form phoshoserine.
Phosphoserine phosphatase removes the phosphate, forming serine. Major site of synthesis are in the liver and kidney. |
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13. Degradation of serine
Two ways... |
Used by many tissues and is generally degraded by transamination to hydroxypyruvate, followed by reduction and phosphorylation to form 2-phosphoglycerate, and intermediate of glycolysis that eventually forms pyruvate.
Can also undergo β-elimination of its hydroxyl group, catalyzed by serine dehydratase, to form pyruvate, directly |
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14. What regulates serine levels in the body?
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When serine levels fall, serine synthesis is increased by induction of 3-phosphoglycerate dehydrogenase and by release of the feedback inhibition of phosphoserine phosphatase.
When serine levels rise, synthesis of serine decreases b/c synthesis of the dehydrogenase is repressed and the phosphatase is inhibited. |
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15. Synthesis of glycine
Major and minor routes? |
Can be synthesized from serine, and to a minor extent, threonine.
Major route from serine is by a reversible reaction that involves FH4 and pyridoxal phosphate. Minor route involves threonine degradation. |
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16. Degradation of glycine
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Converted to glyoxylate by the enzyme D-amino acid oxidase. Once glyoxylate is formed, it can be oxidized to oxalate, which is sparingly soluble and tends to precipitate in the kidney tubules.
Although glyoxalate can be transaminated back to glycine, this is not really considered a biosynthetic route for new glycine. Generation of energy from glycine occurs thru a dehydrogenase that oxidizes glycine to CO2, ammonia, and a carbon that is donated to tetrahydrofolate. |
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17. Synthesis of cysteine
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The carbons and nitrogen for cysteine synthesis are provided by serine, and the sulfur is provided by methionine.
Serine reacts w/homocysteine to form cystathionine, which is catalyzed by cystathionine β-synthase. Cleavage of cystathionine by cystathionase produces cysteine and α-ketobutyrate, which forms succinyl CoA via propionyl CoA. Both enzymes require PLP. |
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18. Regulation of cysteine
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Cysteine inhibits cystathionine β-synthase and, therefore, regulates its own production to adjust fo rthe dietary supply of cysteine.
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19. Degradation of cysteine
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The nitrogen is converted to urea, the carbons to pyruvate, and the sulfur to sulfate, which has two potential fates.
Can generate sulfuric acid or an activated form of sulfate known as PAPS, which is used as a sulfate donor in modifying carbs or AAs in various structures and proteins in the body. |
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20. Synthesis and degradation of homocysteine
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Methionine converts to form homocysteine.
Homocysteine converts to form cysteine. B/c this is the only degradative route for homocysteine, vitamin B6 deficiency or congenital cystathionine β-synthase deficiency can result in homocystinemia, which is associated w/cardiovascular disease. |
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21. Synthesis and degradation of alanine
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Produced from pyruvate by a transamination reaction catalyzed by alanine aminotransaminase (ALT) and may be converted back to pyruvate by a reversal of the same reaction.
Alanine is the major gluconeogenic AA b/c it is produced in many tissues for the transport of nitrogen to the liver. |
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22. Amino acids related to TCA cycle intermediates
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Two groups are syntehsized from TCA cycle intermediates:
1. Group from α-ketoglutarate 2. Group from oxaloacetate During degradation, four groups of AAs are converted to the TCA cycle intermediates and α-ketoglutarate, oxaloacetate, succinyl CoA, and fumarate. |
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23. Synthesis of glutamate
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Five carbons of glutamate are derived from α-ketoglutarate either by transmaination or by the glutamate dehydrogenase reaction.
B/c α-ketoglutarate can be synthesized from glucose, all of the carbons of glutamate can be obtained from glucose. |
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24. Degradation of glutamate
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It is converted back to α-ketoglutarate and leads to the formation of malate, which produces glucose via gluconeogenesis.
Thus, glutamate can be derived from glucose and reconverted to glucose. |
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25. Importance of glutamate
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A. Used for the synthesis of:
1. Glutamine 2. Proline 3. Ornithine 4. Arginine B. Provides the glutamyl moiety of glutathione, an important antioxidant. |
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26. Synthesis of glutamine
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Produced from glutamate by glutamine synthetase, which adds NH4+ to the carboxyl group of the side chain, forming an amide.
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27. Degradation of glutamine
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It's reconverted to glutamate by a different enzyme, glutaminase, which is particularly important in the kidney.
The ammonia it produces enters the urine and can be used as an expendable cation to aid in the excretion of metabolic acids. |
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28. Synthesis of proline
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First, glutamate is phosphorylated and then converted to glutamate 5-semialdehyde by reduction of the side chain carboxyl group to an aldehyde.
This semialdehyde spontaneously cyclizes. Reduction of this cyclic compound yields proline. |
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29. Degradation of proline
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Proline is converted back to glutamate semialdehyde, which is then oxidized to form glutamate.
The synthesis and degradation of proline use different enzymes even though the intermediates are the same. |
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30. Synthesis of arginine
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Synthesized from glutamate via glutamate semialdehyde, which is transmainated to form ornithine, and intermediate of the urea cycle.
The reactions of the urea cycle then produce arginine. Important to realize that if arginine is used for protein synthesis, the levels of ornithine will drop, thereby slowing the urea cycle. This will stimulate the formation of ornithine from glutamate. |
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31. Degradation of arginine
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Arginine is cleaved by arginase to form urea and ornithine.
If ornithine is present in excess of those required for the urea cycle, it is transaminated to glutamate semialdehyde, which is reduced to glutamate. This reaction requires PLP. |
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32. Synthesis and degradation of histidine
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Although histidine cannot be synthesized in humans, five of its carbons form glutamate when it is degraded.
In a series of steps, histidine is converted to formiminoglutamate (FIGLU) Then, later reactions transfer one carbone of FIGLU to the tetrahydrofolate pool, and release NH4+ and glutamate. |
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33. Which two amino acids are related to oxaloacetate?
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1. Aspartate
2. Asparagine |
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34. Synthesis of aspartate
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Produced by transamination of oxaloacetate.
This reaction is readily reversible, so aspartate can be reconverted to oxaloacetate. |
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35. Degradation of aspartate
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Major route involves its conversion to oxaloacetate, however; carbons from aspartate can form fumarate in the urea cycle.
This reaction generates cytosolic fumarate, which must be converted to malate for transport into the mitochondria for oxidatative or anaplerotic purposes. Analogous reaction occurs in the purine nucleotide cycle. Aspartate reacts w/inosine monophosphate to form an intermediate that is then cleaved, forming adenosine monophosphate (AMP) and fumarate. |
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36. Synthesis and degradation of phenylalanine and tyrosine
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Phenylalanine is converted to tyrosine by a hydroxylation reaction.
Tyrosine, produced from phenylalanine or obtained form teh diet, is oxidized, ultimately forming acetoacetate and fumarate. Deficiencies of different enzymes in the pathway result in phenylketonuria, tyrosinemia, and alcaptonuria |
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37. How is phenylalanine converted to tyrosine?
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Using a mixed function oxidase, phenyalanine hydroxylase (PAH), which requires molecular oxygen and tetrahydrobiopterin. The tetrahydrobiopterin is converted to dihydrobiopterin by this reaction.
Dihydrobiopterin must be reconverted back to tetrahydrobiopterin for the reaction to continue to produce tyrosine. |
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38. Degradation of tryptophan
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Trytophan is oxidized to produce alanine, formate, and acetyl CoA. Tryptophan, is , therefore, both glucogenic and ketogenic.
NAD and NADP can be produced from the ring structure of tryptophan. Therefore, tryptophan "spares" the dietary requirement for niacin. The higher the dietary levels of tryptophan, the lower are the levels of niacin required to prevent symptoms of deficiency. |
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39. Degradation of threonine
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Major route is by threonine dehydratase
Minor route is by threonine aldolase which produces glycine and acetyl CoA in the liver |
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40. Degradation of isoleucine
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Produces both succinyl CoA and acetyl CoA
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41. Degradation of leucine
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Leucine is purely ketogenic produces hydroxyymethylgutaryl CoA, which is cleaved to form acetyl CoA and the ketone body acetoacetate.
Most of the tissues in which it is oxidized can use ketone bodies, with the exception of the liver. As with valine and isoleucine, leucine is a universal fuel, with its primary metabolism occurring in muscle. |
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42. Degradation of lysine
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Cannot be directly transaminated at either of its two amino groups
Degraded by a complex pathway in which sacchorpine, α-ketoadipate, and crotonyl CoA are intermediates. During the degradation pathway, NADH and FADH2 are generated for energy. Ultimately lysine generates acetyl CoA and its strictly ketogenic. |
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43. Significance of oxalate
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Produced from glycine or obtained from the diet; forms precipitates with calcium.
Kidney stones are often composed of calcium oxalate. A lack of the transaminase that can convert glyoxylate to glycine leads to the disease primary oxaluria type I. This disease has a consequence of renal failure attributable to excessive accumulation of oxalate in the kidneys. |
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44. Cystathionuria
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The presence of cystathionine in the urine.
Relatively common in premature infants. As they mature, cystathionase levels rise and the levels of cystathionine in the urine decrease. In adults, a genetic deficiency of cystathionase causes cystathionuria. Can happen in genetically normal people from a dietary deficiency of pyridoxine (vitamin B6), because cystathionase requires PLP. |
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45. Cystinuria
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Rare disorder inolving a defect in the transport proteins for cystine, lysine, arginine, and ornithine inot intestinal epithelial cells and that permits resorption of these amino acids by renal tubular cells.
Can form kidney stones. |
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46. Cystinosis
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A rare disorder caused by a defective carrier that normally transports cystine across the lysosomal membrane from lysosomal vesicles to the cytosol.
Cystine accumulates in the lysosomes in many tissues and forms crystals, impairing their function. Children w/this disorder develop renal failure by 6-12 years of age. |
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47. How can one conclude that a patient has homocystinuria caused by an enzyme deficiency?
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If the blood levels of methionine and homocysteine are very elevated and cystine is low, cystathionine-β synthase could be defective.
A measurement of serum cystathionine levels would help to distinguish between a cystathionase or cystathionine β-synthase deficiency. |
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48. Significance of asparagine
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Certain types of tumor cells, particularly leukemic cells, require asparagine for their growth.
Therefore, asparaginase has been used as an antitumor agent. It acts by converting asparagine to aspartate in the blood, decreasing the amount of asparagine available to tumor cell growth. |
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49. Thiamine deficiency
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Leads to an accumulation of α-keto acids in the blood b/c of an inability of pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and branched chain α-keto acid dehydrogenase to catalyze their reactions.
Can result from chronic alcoholism causing ketoacidosis from the accumulations of these α-ketoacids in his blood. |
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50. What compounds form succinyl CoA via propionyl CoA and methymalonyl CoA
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In addition to methionine, threonine, isoleucine, and valine, the last three carbons at the ω-end of odd chain fatty acids form succinyl CoA by this route.
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51. Maple syrup urine disease
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The branched-chain α-keto acid dehydrogenase that oxidatively decarboxylates the branched chain AA's is defective.
As a result, the branched chain AAs and their α-keto analogs accumulate. They appear in the urine, giving it the odor of maple syrup. The accumulation of α-keto acids leads to neurologic complications |
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52. Alcaptonuria
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Occurs when homogentisate, and intermediate in tyrosine metabolism, cannot be further oxidized b/c the next enzyme in the pathway, homogentisate oxidase, is defective.
Homogentisate accumulates and auto-oxidizes, forming a dark pigment, which discolors the urine and stains the diapers of affected infants. Later in life, the chronic accumulation of this pigment in cartilage may cause arthritic joint pain. Blue/black pigmentation present in ears/nose and cheeks |
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53. Tyrosinemia I
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Caused by a genetic deficiency of fumarylacetoacetate hydrolase.
The acute form is associated w/liver failure, a cabbage-like body odor, and death within the first year of life. |
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54. Tyrosinemia II
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Caused by a genetic deficiency of tyrosine aminotransferase and may lead to lesions of the eye and skin as well as neurologic problems.
Patients are treated w/a low tyrosine, low phenylalanine diet. |
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55. Transient tryosinemia
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Freq observed in newborn infants, esp those that are premature.
Biochemical defect is most likely a low level, attributable to immaturity, of 4-hydroxyphenylpyruvate dioxygenase. B/c this enzyme requires ascorbate, ascorbate supplementation also aids in reducing circulating tyrosine levels |
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56. Pellagra
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If the dietary levels of niacin and trytophan are insufficient, the condition known as pellagra results.
The symptoms are dermatitis, diarrhea, dementia, and finally, death. In addition, abnormal metabolism of tryptophan occurs in a vitamin B6 deficiency. |
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57. Respiratory distress syndrome (RDS)
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AKA hyaline membrane disease.
Occurs primarily in the immature lung. Caused by a deficiency of the pulmonary surfactant synthesized by type II pneumocytes. Type II pneumocytes are most abundant after 35 wks gestation. Decreased surfactant results in increased alveolar surface tension, progressive alveolar atelectasis, and increasing inspiratory pressures required to expand alveoli |
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58. Consequences of RDS
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Hypoxemia results in acidosis, pulmonary vasoconstriction, pulmonary hypoperfusion, capillary endothelial and alveolar epithelial damage, and plasma leakage into alveoli.
Plasma proteins combine w/fibrin and necrotic alveolar pneumocytes to form hyaline membranes. |
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59. Morphology of RDS
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Grossy, lungs are solid, airless, and reddish purple.
Microscopically, alveoli are poorly developed and freq collapsed. Proteinaceous membranes line respiratory bronchioles, alveolar ducts, and random alveoli. |
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60. Clinical presentation of RDS
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Typical infant is preterm but appropriate for gestational age.
Associated w/maternal diabetes (surfactant synthesis is suppressed by high insulin levels) and cesarean section) Can measure amniotic fluid phospholipids to assess fetal surfactant synthesis. If low, prophylactic admin of surfactant at birth to extremely premature neonates and symptomatic admin to older premature neonates is highly beneficial. |
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61. Necrotizing enterocolitis (NEC)
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Most commonly occurs in premature infants; the incidence is inversely proportional to gestational age.
Intestinal ischemia is a prerequisite, other predisposing conditions include bacterial colonization of the gut and administration of formula feeds, both of which aggravate mucosal injury in immature bowel |
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62. Clinical course of NEC
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Includes bloody stools, abdominal distention and development of circulatory collapse.
Gas is often present in the intestinal wall (pneumatosis intestinalis). NEC typically involves the terminal ileum, cecum, and right colon. Resection usually required. |
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63. Immune hydrops
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Occurs when the fetus inherits erythrocyte antigens form the father that the mother lacks. A small transplacental bleed allows fetal erythrocytes to enter the maternal circulation where they induce antibody production.
These maternal antibodies then cross the placenta after multiple exposures and this results in erythrocyte lysis in the newborn. |
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64. Although ABO incompatibility is more common than Rh incompatibility, hemolytic disease severe enough to require treatment is rare in such mismatches because...?
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1. Most anti-A and anti-B antibodies are IgM and do not cross the placenta
2. Neonatal RBCs poorly express A and B blood group antigens. 3. Many cells in addition to RBCs express A and B antigens and therefore adsorb antibody that enters the fetal bloodstream. |
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65. Three major causes of nonimmune hydrops
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1. Cardiovascular defects
2. Chromosomal anomalies (turner syndrome, trisomies 21 and 18) 3. Fetal anemia unrelated to immune hemolysis (e.g. β˚β˚ thalassemia) * Transplacental infection by parvovirus B19 is also rapidly emerging as an important cause of hydrops; the virus enters and replicates within erythroid precursors (normoblasts), leading to erythrocyte maturation arrest and aplastic anemia. |
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66. Hydrops associated w/fetal anemia
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1. Both fetus and placenta are characteristically pale
2. The liver and spleen are enlarged from cardiac failure and congestion 3. Bone marrow demonstrates compensatory hyperplasia of erythroid precursors 4. Extramedullary hematopoiesis occurs in liver, spleen, and occasionally other tissues. 5. Increased hematopoiesis results in large numbers of immature RBCs in the peripheral blood, hence the name erythroblastosis fetalis |
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67. Phenylketonuria PKU
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Approx 50% of dietary phenylalanine is required for protein synthesis; the remainder is converted into tyrosine by the phenylalanine hydroxylase system.
Homozygotes for one of several different mutations in the PAH gene have variable enzymatic deficiencies and consequently variable elevated phenylalanine Most freq mutation is classic PKU and is relatively common in people of Scandinavian descent and uncommon in blacks and Jews. |
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68. Characteristics of PKU
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Although normal at birth, affected individuals exhibit rising plasma phenylalanine w/in the first few weeks of life, followed by impaired brain development and mental retardation.
Screening at birth for abnormally elevated urinary levels of various phenylalanine metabolites allows early diagnosis. Subsequent phenylalanine dietary restriction prevents most clinical sequelae. |
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69. Benign hyperphenylalanemia
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Some mutations int eh PAH gene result in a partial enzyme deficiency and therefore only moderately elevated phenylalanine levels.
Such patients suffer no neurologic sequelae. |
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70. Galactosemia
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Dietary lactose, is split into glucose and galactose by lactase; galactose is then converted to glucose by three additional enzymes.
The most common and clinically significant form of galactosemia is autosomal recessive, resulting from mutation in galactose-3-phosphate uridyl transferase (GALT) Affected patients accumulate galactose-1-phosphate. |
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71. Clinical picture of galactosemia
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Variable, corresponding to distinct mutations in GALT.
Overall, infants fail to thrive, and present with vomiting and diarrhea after milk ingestion. Liver, eyes and brain are most severely affected; changes include hepatomegaly due to hepatic fat accumulation, followed by cirrhosis, cataracts, and nonspecific alterations in the CNS (including mental retardation) |
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72. Treatment for galactosemia
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Urinary screening at birth reveals the presence of an abnormal reducing sugar.
Removal of dietary galactose for at least the first two years of life prevents most of the clinical and morphologic sequelae. |
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73. Cystic fibrosis (CF)
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Most common lethal genetic disease affecting whites.
It affects epithelial ion transport resulting in abnormal fluid secretion in exocrine glands and in respiratory, GI and reproductive mucosa. |
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74. Gene responsible for CF and consequences of mutations in this gene
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The gene responsible for CF encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein.
CFTR regulates the movement of multiple ions as well as affecting other cellular processes; however, CFTR is primarily a chloride channel, and mutations in the CFTR gene disrupt epithelial chloride transport. Thus, normal sweat ducts require CFTR for resorption of chloride; inability to resorb chloride causes increased sweat chloride concentration |
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75. CFTR in the normal and abnormal airways and GI epithelia
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Normal airway and GI epithelial require CFTR for secretion of chloride.
The inability to secrete chloride into the lumen, combined w/increased sodium absorption, causes osmotic resorption of water from the lumen and dehydration of the mucus layer coating the mucosal cells. Defective mucociliary action and the accumulation of hyperconcentrated, viscous secretions ultimately obstruct ductal outflow from the organs. In addition, changes in secretion composition prevents activation of antibacterial defensin produced by epithelium and predisposes patients to recurrent infections. |
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76. CFTR
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Has two transmembrane domains, two nucleotide binding domains, and a regulatory domain that contains protein kinase phosphorylation sites.
Various mutations in the CF gene affect different regions of CFTR, resulting in distinct functional consequences and differing severity of clinical sequelae. |
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77. Most common mutation of CFTR
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A three-nucleotide deletion normally codiing for phenylalanine at position F508;
This results in defective intracellular CFTR processing w/degradation before it reaches the cell surface. Patients homozygous for the F508 mutation have virtual absence of CFTR function; they present w/severe disease. |
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78. CF and pancreas
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Abnormalities occur in 85-90% of patients; they range from mucus accumulation in small ducts w/mild dilation to total atrophy of the exocrine pancreas, leaving only islets within fibrofatty stroma.
Absence of pancreatic exocrine secretions impairs fat absorption; resulting deficiency of vitamin A occurs |
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79. CF and intestines
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Thick viscous plugs of mucus (meconium ileus) may cause small intestinal obstruction
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80. CF and liver
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Plugging of bile canaliculi by mucinous material results in diffuse hepatic cirrhosis.
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81. CF and salivary glands
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Commonly involved w/progressive duct dilation, ductal squamous metaplasia, and glandular atrophy.
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82. CF and lungs
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Involved in most cases and such changes are the most serious complication of CF
Mucus secreting cells hyperplasia and viscous secretions block and dilate bronchioles. Superimposed infections and pulmonary abscesses are common. |
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83. CF and male genital tract
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Azoospermia and infertility occur in 95% of males surviving to adulthood, frequently w/congenital bilateral absence of the vas deferens.
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84. Clinical course of CF
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1. Pancreatic exocrine insufficiency
2. Malabsorption of fats 3. Steatorrhea 4. Fat soluble vitamin deficiencies 5. Cardiorespiratory complications i. chronic cough ii. lung infections iii. COPD iv. cor pulmonale |
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85. Common risk factors of SIDS
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1. Infant sleeping prone
2. Prematurity 3. Low birth weight 4. SIDS in a prior sibling 5. Young maternal age 6. Short intergestational interval 7. Inadequate prenatal care 8. Low SEC status 9. Maternal smoking or drug abuse |
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86. Other factors in SIDS
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Most SIDS babies have an immediate prior history of a mild respiratory tract infection.
Also, developmental immaturity of critical brain stem regions (i.g. arcuate nucleus) involved in arousal and cariorespiratory control may play a role. |
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87. Common autopsy findings in SIDS
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1. Mutiple petechia on thymus, visceral and parietal pleura,and epicardium
2. Histologic evidence of recent infection in the upper respiratory tract. 3. CNS demonstrates astrogliosis of the brain stem and cerebellum 4. Hypoplasia of the arcuate nucleus is reported. |
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88. Heterotopia
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Represents microscopically normal cells or tissues present in abnormal locations
These cells are usually of little significance but may be clinically confused w/true neoplasms |
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89. Hamartomas
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Excessive (but focal) overgrowth of cells and tissues native to the organ or site in which they occur.
They may be considered a link between malformations and neoplasms. |
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90. Hemangiomas
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Most common tumors of infancy; most are cutaneous, particularly on the face and scalp.
They may enlarge along w/the growth of the child, but commonly spontaneously regress. Rarely become malignant |
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91. Lymphangiomas
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May occur on the skin but also within deeper regions of the neck, axilla, mediastinum, and retroperitoneal tissue.
They tend to increase in size and, depending on location, become clinically significant if the encroach on vital structures. Histologically, they are composed of cystic and cavernous lymphatic spaces, with variable numbers of associated lymphocytes. |
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92. Fibrous tumors
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Histologically, fibrous tumors range from sparsely cellular proliferations (fibromatosis) to richly cellular lesions indistinguishable from adult fibrosarcomas.
In contrast to fibrous tumors occurring in adults, the histologic picture does not predict the biology and an individual tumor (they may spontaneously regress) |
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93. Teratomas
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Teratoma indicidence has two peaks: at age 2, and again in late adolescence.
Those occurring in childhood and infancy tend to occur in the sacrococcygeal region. |
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94. Sacrococcygeal teratomas
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Approx 10% of sacrococcygeal teratomas are associated w/congenital anomalies, primarily defects of the hindgut and cloacal region and other midline defects.
They are histologically similar to other teratomas; mesodermal, endodermal, and ectodermal elements are present. Approx 75% contain mature tissues only and are benign. |
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95. In what three ways do childhood malignancies differ biologically and histologically from their adult counterparts?
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1. A close relationship between abnormal development (teratogenesis) and tumor induction (oncogenesis)
2. A greater prevalence of underlying familial or genetic germ line aberrations 3. A tendency for some malignancies in the fetal or neonatal period to regress spontaneously or cytodifferentiate. |
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96. What are the most frequent childhood cancers?
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Those that arise in the hematopoietic system (leukemia, some lymphomas), CNS, adrenal medulla, retina, soft tissue, bone and kidney.
Leukemia accounts for more deaths in children younger than 15 years of age than all other tumors combined |
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97. Neuroblastic tumors
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Most neuroblastic tumors occur in children younger than 5, and arise int he adrenal medulla or various sympathetic ganglia.
Most common subtype is neuroblastoma, characterized by sheets of small, round blue neuroblasts within a neurofibrillary background an dchacteristic Homer-Write pseudorosettes. Approx 90% of neuroblastomas produce catecholamines; elevated blood or urine catecholamine metabolites are important diagnostic features. |
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98. What are the most important factors in childhood neoplasms?
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Age and stage
Infants (<12 months) have an excellent prognosis regardless of stage, but children older than 5 usually have extremely poor outcomes. |
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99. Other favorable/unfavorable factors important in prognosis of childhood neoplasms
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1. Histological features (schwannian stroma is favorable)
2. Tumor ploidy (diplody, near-diploidy, or near-tetraploidy are unfavorable 3. N-myc amplification (unfavorable) 4. 17q gain and 1p loss (unfavorable) 5. Telomerase overexpression (unfavorable) 6. TrkA expression (favorable) |
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100. WIlms tumor
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Wilms tumor of the kidney is usually Dx'ed between 2 and 5 y/o.
Although malignant, the overall survival rate is > 90%. Although 90% are sporadic, there are associations with three groups of malformation syndromes, all involving chromosome 11p |
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101. Three groups of malformation syndromes, all involving chromosome 11p
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1. WAGR (Wilms tumor, aniridia, genital anomalies, mental retardation). Patients have a 33% chance of developing Wilms tumors
2. Denys-Drash syndrome; patients have gonadal dysgenesis and nephropathy leading to renal failure; most develop Wilms tumors 3. Beckwith-Wiedemann syndrome -Patieitns have enlarge body organs, hemihypertrophy, renal medullary cysts, adrenal cytomegaly and a predisposition to developing Wilms and other primitive tumors WAGR inolves dletion on chromosome 11p band 12 |
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102. Morphology of Wilms tumors
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They are soft, large, well circumscribed renal massed characterized by triphasic histological features:
1. Blastema 2. Immature stroma 3. Tubules - an attempt to recpitulate nephrogenesis. |
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103. Nervous system development
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The nervous system arises from the neural plate, which is a dorsal ectodermal thickening that appears on about the 16th day of gestation. By the sixth week, part of the neural tube becomes the cerebral vesicle, which later becomes the cerebral hemispheres
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104. Development of the brain and cerebral cortex
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The cerebral cortex begins to develop by the 10th week, but layers do not appear until the sixth month of pregnancy; the sensory cortex and the motor cortex are formed before the association cortex.
Some brain function has been detected in utero by fetal encephalographic responses to sound. The human brain weighs about 350 g at birth and 1,450 g at full adult development, a fourfold increase, mainly in the neocortex. This increase is almost entirely because of the growth in the number and branching of dendrites establishing new connections. After birth, the number of new neurons is negligible. |
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105. Pruning
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Pruning refers to the programmed elimination during development of neurons, synapses, axons, and other brain structures from the original number, present at birth, to a lesser number.
Thus, the developing brain contains structures and cellular elements that are absent in the older brain. The fetal brain generates more neurons than it will need for adult life. |
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106. Purpose of pruning
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Pruning occurs to rid the nervous system of cells that have served their function in the development of the brain.
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107. Maternal stress
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Maternal stress correlates with high levels of stress hormones (epinephrine, norepinephrine, and adrenocorticotropic hormone) in the fetal bloodstream, which act directly on the fetal neuronal network to increase blood pressure, heart rate, and activity level.
Mothers with high levels of anxiety are more likely to have babies who are hyperactive, irritable, and of low birthweight and who have problems feeding and sleeping than are mothers with low anxiety levels. A fever in the mother causes the fetus's temperature to rise. |
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108. Fetal alcohol syndrome
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1. Growth retardion of prenatal origin
2. Microphtalmia 3. Short palpebral fissues 4. Midface hypoplasia 5. Smooth or short philtrum 6. Thin upper lip 7. Microcephaly 8. Cognitive deficits 9. Seizures |
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109. Alcohol and ADHA
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Some studies suggest that alcohol use during pregnancy may contribute to attention-deficit hyperactivity disorder (ADHD).
Animal experiments have shown that alcohol reduces the number of active dopamine neurons in the midbrain area and ADHD is associated with reduced dopaminergic activity in the brain. |
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110. Maternal smoking
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Smoking during pregnancy is associated with both premature births and below-average infant birthweight.
Some reports have associated sudden infant death syndrome (SIDS) to be associated with mothers who smoke. |
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111. Premature infants
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Premature infants are defined as those with a gestation of less than 34 weeks or a birthweight under 2,500 g (5.5 lb).
Such infants are at increased risk for learning disabilities, such as dyslexia, emotional and behavioral problems, mental retardation, and child abuse. |
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112. Postmature infants
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Postmature infants are defined as infants born 2 weeks or more beyond the expected date of birth.
The postmature baby typically has long nails, scanty lanugo hair, more scalp hair than usual, and increased alertness. |
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113. Reflexes present at birth
Which ones disappear as the child gets older? |
1. Rooting reflex (puckering of lips in response to perioral stimualtion
2. Grasp reflex 3. Plantar (Babinski) reflex 4. Knee reflex 5. Startle (Moro) reflex 6. Tonic neck reflex In normal children, the grasp reflex, the startle reflex, and the tonic neck reflex disappear by the fourth month. The Babinski reflex usually disappears by the 12th month. |
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114. Smiling response in newborns
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The smiling response occurs in two phases:
1. First phase is endogenous smiling, which occurs spontaneously within the first 2 months and is unrelated to external stimulation 2. Second phase is exogenous smiling, which is stimulated from the outside, usually by the mother, and occurs by the 16th week. |
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115. Piaget's stages of cognitive development
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1. Sensorimotor (birth - 2 years)
2. Preoperational (2- 7 years) 3. Concrete operational (7-11 years) 4. Formal operational (11+ yrs) |
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116. 6 substages of sensorimotor stage
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1. Reflexes (0-1 month)
2. Primary Circular Reactions (1-4 months): -This substage involves coordinating sensation and new schemas. 3. Secondary Circular Reactions (4-8 months): -The child becomes more focused on the world and begins to intentionally repeat an action in order to trigger a response in the environment. 4. Coordination of Reactions (8-12 months): -The child starts to show clearly intentional actions. The child may also combine schemas in order to achieve a desired effect. 5. Tertiary Circular Reactions (12-18 months): -Children begin a period of trial-and-error experimentation 6. Early Representational Thought (18-24 months): -Children begin to develop symbols to represent events or objects in the world/ make believe play |
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117. Preoperational stage
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2-7 yrs
1. Language development is one of the hallmarks of this period. 2. Do not yet understand concrete logic, cannot mentally manipulate information 3. Egocentrism -unable to take the point of view of other people 4. Conservation -Piaget found that few children showed any understanding of conservation prior to the age of five |
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118. Concrete operational stage
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7-11 years
During this time, children gain a better understanding of mental operations. Children begin thinking logically about concrete events, but have difficulty understanding abstract or hypothetical concepts. One of the most important developments in this stage is an understanding of reversibility, or awareness that actions can be reversed. Conservation is apparent |
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119. Formal operational stage
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11 years onward
Includes concepts: 1. Hypothetical-deductive reasoning; adolescent quick thinking or excuses 2. Imaginary audience; everyone is looking at them 3. Personal fable; inflated opinion of themselves 4. Propositional thinking; logic Abstraction and reason- Can think of all possibilities |
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120. Harry Harlow's experiment
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Studied social learning and the effects of social isolation in monkeys.
The monkeys preferred the terry-cloth surrogates, which provided contact and comfort, to the feeding surrogate. The results of Harlow's experiments were widely interpreted as indicating that infant attachment is not simply the result of feeding. |
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121. Secure attachment
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Children show fewer adjustment problems; however, these children have typically received more consistent and developmentally appropriate parenting for most of their life.
The parents of securely attached children are likely better able to maintain these aspects of parenting through a divorce. |
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122. Insecure/Avoidant attachment
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Children become anxious, clinging, and angry with the parent.
These children typically come from families with adults who were also insecurely attached to their families and, thus, were unable to provide the kind of consistency, emotional responsiveness, and care that securely attached parents could offer. Such parents have a more difficult time with divorce, and are more likely to become rejecting. |
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123. Insecure/Ambivalent attachment
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Children generally are raised with disorganized, neglecting, and inattentive parenting.
The parents are even less able to provide stability and psychological strength for them after a divorce and, as a result, the children are even more likely to become clinging but unconsolable in their distress, as well as to act out, suffer mood swings, and become oversensitive to stress. |
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124. John Bowlby
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John Bowlby studied the attachment of infants to mothers and concluded that early separation of infants from their mothers had severe negative effects on children's emotional and intellectual development
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125. Mary Ainsworth
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Mary Ainsworth expanded on Bowlby's observations and found that the interaction between mother and baby during the attachment period influences the baby's current and future behavior significantly.
Unresponsive mothers produce anxious babies. |
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126. Secured base effect
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Ainsworth also confirmed that attachment serves to reduce anxiety.
The secured base effect enables a child to move away from the attachment figure and explore the environment. Inanimate objects, such as a teddy bear or a blanket, also serve as a secure base, one that often accompanies children as they investigate the world. |
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127. What are the main determinants of secure attachment?
Insecure attachment? |
1. Maternal sensitivity
2. Maternal responsiveness However, when the attachment is insecure, they type of insecurity (avoidant, anxious, ambivalent) is determined by infant temperament. |
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128. Social Deprivation Syndromes and Maternal Neglect
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Infants in institutions characterized by low staff-to-infant ratios and frequent turnover of personnel tend to display marked developmental retardation, even with adequate physical care and freedom from infection.
The same infants, placed in adequate foster or adoptive care, exhibit marked acceleration in development. |
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129. Stranger anxiety
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A fear of strangers is first noted in infants at about 26 weeks of age, but is not fully developed until about 32 weeks (8 months). At the approach of a stranger, infants cry and cling to their mothers. Babies exposed to only one caregiver are more likely to have stranger anxiety than are those exposed to a variety of caregivers.
Stranger anxiety is believed to result from a baby's growing ability to distinguish caregivers from all other persons. |
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130. Separation anxiety
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Occurs between 10 and 18 months of age, is related to stranger anxiety but is not identical to it. Separation from the person to whom the infant is attached precipitates separation anxiety.
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131. Stages of separation-individuation proposed by Mahler
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1. Normal autism (birth-2 mos)
2. Symbiosis (2-5 mos) 3. Differentiation (5-10 mos) 4. Practicing (10-18 mos) 5. Rapprochement (18-24 mos) 6. Object constancy (2-5 yrs) |
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132. Difficult children
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Make up 10 percent of all children, have a hyperalert physiological makeup.
They react intensely to stimuli (cry easily at loud noises), sleep poorly, eat at unpredictable times, and are difficult to comfort. |
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133. Easy children
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Easy children, who make up 40 percent of all children, are regular in eating, eliminating, and sleeping; they are flexible, can adapt to change and new stimuli with a minimum of distress, and are easily comforted when they cry.
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134. Goodness of fit and child type
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The difficult child is harder to raise and places greater demands on the parent than the easy child.
Chess and Thomas used the term goodness of fit to characterize the harmonious and consonant interaction between a mother and a child in their motivations, capacities, and styles of behavior. Poor fit is likely to lead to distorted development and maladaptive functioning. |
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135. Good-enough mothering
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Winnicott believed that infants begin life in a state of nonintegration, with unconnected and diffuse experiences, and that mothers provide the relationship that enables infants' incipient selves to emerge. Mothers supply a holding environment in which infants are contained and experienced.
The mother need not be perfect, but she must provide good-enough mothering. |
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136. Toddler negativism
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Toddlers' negativism is vital to the development of independence, but if it persists, oppositional behavior connotes a problem.
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137. Social referencing
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In the second year
Social referencing is often apparent at this age; the child looks to parents and others for emotional cues about how to respond to novel events. |
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138. Potty training trend in US
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The trend in the United States has been toward delayed training, but in the last few years this trend appears to be shifting back to early training.
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139. Play patterns in preschool
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In the preschool years, children begin to distinguish reality from fantasy, and play reflects this growing awareness.
Pretend games are popular and help test real-life situations in a playful manner. Dramatic play in which children act out a role such as a housewife or a truck driver, is common |
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140. Play patterns between 2-4 yrs
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Children commonly engage in parallel play, solitary play alongside another child with no interaction between them.
By age 3, play is often associative, that is, playing with the same toys in pairs or in small groups, but still with no real interaction among them. By age 4, children are usually able to share and engage in cooperative play. Real interactions and taking turns become possible. |
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141. Imaginary companions
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Imaginary companions most often appear during preschool years, usually in children with above-average intelligence and usually in the form of persons.
Their significance is not clear, but these figures are usually friendly, relieve loneliness, and reduce anxiety. In most instances, imaginary companions disappear by age 12, but they can occasionally persist into adulthood. |
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142. Latency period
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Although the middle years have sometimes been referred to as a latency period, a moratorium on psychosexual exploration and play until the eruption of sexual impulses with puberty.
It is now recognized that a considerable amount of sexual interest continues through these years. |
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143. Chum period
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Harry Stack Sullivan postulated that a chum, or buddy, is an important phenomenon during the school years.
By about 10 years of age, children develop a close same-sex relationship, which Sullivan believed is necessary for further healthy psychological growth. Moreover, Sullivan believed that the absence of a chum during the middle years of childhood is an early harbinger of schizophrenia. |
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144. School refusal
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Some children refuse to go to school at this time, generally because of separation anxiety. A fearful mother may transmit her own fear of separation to a child, or a child who has not resolved dependence needs panics at the idea of separation.
School refusal is usually not an isolated problem; children with the problem typically avoid many other social situations. |
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145. Dream sleeping in childhood
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Periods of REM occur about 60 percent of the time during the first few weeks of life, a period when infants sleep two thirds of the time.
Premature babies sleep even longer than full-term babies, and a greater proportion of their sleep is REM sleep. The sleep-wake cycle of newborns is about 3 hours long. Among adults, the dream-to-sleep ratio is stable: 20 percent of sleeping time is spent dreaming. Even newborns have brain activity similar to that of the dreaming state. |
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146. Studies of children from large families
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Studies of children from large families (of four or five children) show that they are more likely to have conduct disorder and to have a slightly lower level of verbal intelligence than children from small families.
Decreased parental interaction and discipline may account for these findings. |
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147. Frank Sulloway and birth order
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According to Frank Sulloway, firstborn children tend to be conservative and conformists; by contrast, youngest children tend to be independent and rebellious in regard to family and cultural norms.
Sulloway found that a high proportion of prominent persons were lastborn children. He ascribes these differences to birth order and suggests that each child develops personality traits to fit an unfilled slot in the family. His findings need to be replicated. |
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148. Three types of step families
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1. Neo-traditional
2. Romantic 3. Matriarchal |
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149. Neo-traditional step families
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Resembles traditional families
Absent biological parent is included at times. Discipline, boundaries and limits, and expectations are discussed openly. Family coalitions and side-taking are better avoided. |
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150. Romantic step families
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Expect to be a traditional family immediately
The absent biological parent is expected to disappear and is often criticized. Stepparent/stepchild difficulties are common. Stress is unbearable. Few open and frank discussions about problems |
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151. Matriarchal step families
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Run by a highly competent mom and her companion follows
Companion is a buddy to the children, not to the parent. Birth of a step-sibling causes problems. |
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152. Parenting styles
Which one is the best? |
1. Authoritarian style
2. Indulgent-permissive style 3. Indulgent-neglectful style 4. *Authoritative-reciprocal style *marked by firm rules and shared decision-making in a warm, loving environment, is believed to be the style most likely to result in self-reliance, self-esteem, and a sense of social responsibility. |
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153. Adaptive functioning
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The conceptualization of mental retardation includes deficits in cognitive abilities as well as in behaviors required for social and personal sufficiency, known as adaptive functioning
Wide acceptance of this definition has led to the consensus that an assessment of both social adaptation and intelligence quotient (IQ) are necessary to determine the level of mental retardation. Measures of adaptive function assess competency in performance of everyday tasks, whereas measures of intellectual function focus on cognitive abilities. |
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154. Deinstitutionalization
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An important force in the deinstitutionalization of children with mental retardation was the philosophy of normalization in living situations and inclusion in educational settings.
Since the late 1960s, few children with mental retardation have been placed in institutional settings, and the concepts of normalization and inclusion became prominent issues among advocacy groups and most citizens. |
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155. American Association on Mental Retardation (AAMR)
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The AAMR, promotes a view of mental retardation as a functional interaction between an individual and the environment, instead of a static description of a person's limitations.
The AAMR promotes designating an IQ of 75, rather than 70, as the beginning level of the mild mental retardation range, thereby enabling many more persons to receive services as mentally retarded. |
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156. Mental retardation
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A significantly subaverage general intellectual functioning that manifests before the age of 18 AND IS accompanied by significant limitations in adaptive functioning in at least 2 of the following:
1.communication 2.self care 3.home living 4.social / interpersonal skills 5.use of community resources 6.self direction 7.functional academic skills 8.work 9.leisure 10.health 11.safety |
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157. Mild mental retardation
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Mild mental retardation (IQ range, 50 to 70) represents approximately 85 percent of persons with mental retardation. In general, children with mild mental retardation are not identified until after first or second grade, when academic demands increase.
By late adolescence, they often acquire academic skills at approximately a sixth grade level. Many adults with mild mental retardation can live independently with appropriate support and raise their own families. |
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158. Moderate mental retardation
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Moderate mental retardation (IQ range, 35-50) represents about 10 percent of persons with mental retardation.
Most children with moderate mental retardation acquire language and can communicate adequately during early childhood. They are challenged academically and often are not able to achieve academically above a second to third grade level. During adolescence, socialization difficulties often set these persons apart, and a great deal of social and vocational support is beneficial. As adults, persons with moderate mental retardation may be able to perform semiskilled work under appropriate supervision. |
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159. Severe mental retardation
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Severe mental retardation (IQ range, 20-35) comprises about 4 percent of individuals with mental retardation.
They may be able to develop communication skills in childhood and often can learn to count as well as recognize words that are critical to functioning. In this group, the cause for the mental retardation is more likely to be identified than it is in milder forms of mental retardation. In adulthood, persons with severe mental retardation may adapt well to supervised living situations, such as group homes, and may be able to perform work-related tasks under supervision. |
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160. Profound mental retardation
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Profound mental retardation (IQ range below 20) constitutes approximately 1 to 2 percent of persons with mental retardation.
Most individuals with profound mental retardation have identifiable causes for their condition. Children with profound mental retardation may be taught some self-care skills and learn to communicate their needs given the appropriate training. |
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161. Epidemiology of mental retardation
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The prevalence of mental retardation at any one time is estimated to range from 1 percent to 3 percent of the population. The incidence of mental retardation is difficult to calculate because mild mental retardation sometimes goes unrecognized until middle childhood.
In some cases, even when intellectual function is limited, good adaptive skills are not challenged until late childhood or early adolescence, and the diagnosis is not made until that time. The highest incidence is in school-age children, with the peak at ages 10 to 14 years. Mental retardation is about 1.5 times more common among men than among women. |
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162. Comorbitiy of mental retardation
With mild/moderate/severe/profound mental retardation? |
Epidemiological surveys indicate that up to two thirds of children and adults with mental retardation have comorbid mental disorders; this rate is several times higher than that in the community samples of those not mentally retarded.
Disruptive and conduct-disorder behaviors occurred more commonly in the mildly retarded group; the more severely retarded group exhibited psychiatric problems more often associated with autistic disorder, such as self-stimulation and self-mutilation. Those with profound mental retardation were less likely to exhibit psychiatric symptoms. |
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163. Highly prevalent psychiatric symptoms that can occur in mentally retarded persons outside the context of a mental disorder are...?
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1. Hyperactivity
2. Short attention span 3. Self injurious behaviors 4. Repetitive stereotypical behaviors |
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164. Relationship between mental retardation, epilepsy and autistic spectrum disorders
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In a recent review of psychiatric disorders in children and adolescents with mental retardation and epilepsy, approximately one
third also had autistic disorder or an autistic-like condition. The combination of mental retardation, active epilepsy, and autism or an autistic-like condition occurs at a rate of 0.07 percent in the general population. |
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165. Most common chromosomal and metabolic disorders that cause mental retardation
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Among chromosomal and metabolic disorders, Down syndrome, fragile X syndrome, and phenylketonuria (PKU) are the most common disorders that usually produce at least moderate mental retardation.
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166. Genetic etiological factors in mental retardation
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Abnormalities in autosomal chromosomes are frequently associated with mental retardation, whereas aberrations in sex chromosomes can result in characteristic physical syndromes that do not include mental retardation (e.g., Turner's syndrome with XO and Klinefelter's syndrome with XXY, XXXY, and XXYY variations). Some children with Turner's syndrome have normal to superior intelligence.
Agreement exists on a few predisposing factors for chromosomal disorders; among them, advanced maternal age, increased age of the father, and X-ray radiation. |
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167. Down's syndrome
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Down’s Syndrome – Estimated to be 1/700 births, and increases incidence with age of mother’s over 35 years old. Down’s is equally common among the sexes. Features include;
1. flattened occiput 2. epicanthal folds 3. broad bridge of nose 4. small mouth with protruding tongue 5. tend to be short stature |
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168. Three types of chromosomal aberrations in Down syndrome
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1. Patients with trisomy 21 (three chromosome 21, instead of the usual two) represent the overwhelming majority; they have 47 chromosomes, with an extra chromosome 21.
2. Nondisjunction occurring after fertilization in any cell division results in mosaicism, a condition in which both normal and trisomic cells are found in various tissues 3. In translocation, a fusion occurs of two chromosomes, usually 21 and 15, resulting in a total of 46 chromosomes, despite the presence of an extra chromosome 21. The disorder, unlike trisomy 21, is usually inherited, and the translocated chromosome may be found in unaffected parents and siblings. The asymptomatic carriers have only 45 chromosomes. |
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169. Mental retardation and Down syndrome
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Mental retardation is the overriding feature of Down syndrome. Most persons with the syndrome are moderately or severely retarded, with only a minority having an IQ above 50.
Mental development seems to progress normally from birth to 6 months of age; IQ scores gradually decrease from near normal at 1 year of age to about 30 at older ages. |
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170. Postmortem studies of those with Down syndrome
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Postmortem studies of those with Down syndrome over the age of 40 have shown a high incidence of senile plaques and neurofibrillary tangles, as seen in Alzheimer's disease. Neurofibrillary tangles are known to occur in a variety of degenerative diseases, whereas senile plaques seem to be found most often in Alzheimer's disease and in Down syndrome. Thus, the two disorders may share some pathophysiology.
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171. Fragile X syndrome
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Fragile X is the most common inheritable form of mental retardation, but is a mild case.
Occurrence is about 1/1,000 male births and 1/2,000 female births. Features include; 1. facial dysmorphism, i.e., a. projection of jaw beyond projection of the forehead) b. a high broad forehead 2. autistic traits 3. high rates of ADD, and ADHD, learning disorder, pervasive developmental disability |
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172. Other features of Fragile X syndrome
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Persons with fragile X syndrome seem to have relatively strong skills in communication and socialization; their intellectual functions seem to decline in the pubertal period.
Female carriers are often less impaired than males with fragile X syndrome, but females can also manifest the typical physical characteristics and can be mildly retarded. |
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173. Prader-Willi syndrome
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Prader-Willi syndrome is postulated to result from a small deletion involving chromosome 15 of paternal origin, usually occurring sporadically.
During the first 6-24 months infants tend to be somnolent and hypotonic and eat very little. Prevalence is about 1/10,000. Features beside obesity include; 1. compulsive eating/obesity 2. hypogonadism, micropenis, and cryptorchidism, lack of breast development, and lack of pubic hair, varying degrees of amenorrhea 3. oppositional and defiant behavior, |
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174. Cat's Cry (Cri-du-Chat) syndrome
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Children with cat's cry syndrome lack part of chromosome 5. They are severely retarded and show many signs often associated with chromosomal aberrations, such as microcephaly, low-set ears, oblique palpebral fissures, hypertelorism, and micrognathia.
The characteristic cat-like cry caused by laryngeal abnormalities that gave the syndrome its name gradually changes and disappears with increasing age. |
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175. PKU
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A metabolic disorder results with impaired brain development, and typically severe mental retardation is identified around the 6th month of life.
Fewer than 4% of untreated children achieve IQ’s greater than 50 or 60. About one third are unable to walk, and about two thirds are unable to talk. Verbal communication is severely limited. This condition can be avoided by dietary restriction of phenylalanine intake early in life. Prevalence is about 1/10,000 births, |
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176. Causes of PKU
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The basic metabolic defect in PKU is an inability to convert phenylalanine, an essential amino acid, to paratyrosine because of the absence or inactivity of the liver enzyme phenylalanine hydroxylase, which catalyzes the conversion.
Two other types of hyperphenylalaninemia have recently been described. One is caused by a deficiency of the enzyme dihydropteridine reductase, and the other to a deficiency of a cofactor, biopterin. |
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176. Rett’s disorder
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X-linked dominant mental retardation syndrome that is degenerative and affects only females
Characterized by mental retardation, microcephaly, autistic features, and stereotypical hand movements. Has a prevalence rate of 1/10,000. Infants are apparently normal until the end of their first year. Their normal development exhibits a general slowing, failure to make expected weight gain, failure to progress to crawling, withdraw from social contacts. Most patients are severally retarded. |
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177. Neurofibromatosis
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AKA von Recklinghausen's disease
the most common of the neurocutaneous syndromes caused by a single dominant gene, which may be inherited or be a new mutation. The disorder occurs in about 1 of 5,000 births and is characterized by cafe au lait spots on the skin and by neurofibromas, including optic gliomas and acoustic neuromas, caused by abnormal cell migration. Mild mental retardation occurs in up to one third of those with the disease. |
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178. Tuberous sclerosis
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Can be inherited as an autosomal dominant trait, or due to sporadic mutations.
Classically, presents with childhood triad of mental retardation, seizures and adenoma sebaceum. The phenotypic presentation includes adenoma sebaceum and ash-leaf spots that can be identified with a slit lamp. More frequent among males, and prevalence is rare of about 1/15,000 |
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179. Lesch-Nyhan syndrome
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Lesch-Nyhan syndrome is a rare disorder caused by a deficiency of an enzyme involved in purine metabolism.
The disorder is X-linked; patients have mental retardation, microcephaly, seizures, choreoathetosis, and spasticity. The syndrome is also associated with severe compulsive self-mutilation by biting the mouth and fingers. |
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180. Adrenoleukodystrophy
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The most common of several disorders of sudanophilic cerebral sclerosis, adrenoleukodystrophy is characterized by diffuse demyelination of the cerebral white matter resulting in visual and intellectual impairment, seizures, spasticity, and progression to death. The cerebral degeneration in adrenoleukodystrophy is accompanied by adrenocortical insufficiency.
The disorder is transmitted by a sex-linked gene located on the distal end of the long arm of the X chromosome. Lorenzo's Oil... look it up on IMDb.com |
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181. Infections acquired in the prenatal period
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1. Rubella (German measles)
2. Toxoplasmosis 3. Cytomegalic inclusion disease 4. Syphilis 5. Herpes simplex 6. AIDS |
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182. Cytomegalic inclusion disease
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Some children are stillborn, and others have jaundice, microcephaly, hepatosplenomegaly, and radiographic findings of intracerebral calcification.
Children with mental retardation from the disease frequently have cerebral calcification, microcephaly, or hydrocephalus. The diagnosis is confirmed by positive findings of the virus in throat and urine cultures and the recovery of inclusion-bearing cells in the urine. |
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183. Complications of pregnancy that can result in mental retardation
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Toxemia of pregnancy and uncontrolled maternal diabetes present hazards to the fetus and sometimes result in mental retardation.
Maternal malnutrition during pregnancy often results in prematurity and other obstetrical complications. Vaginal hemorrhage, placenta previa, premature separation of the placenta, and prolapse of the cord can damage the fetal brain by causing anoxia. |
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184. Perinatal issues that can cause mental retardation
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Premature babies with low birth weight (less than 1,000 grams) are at high risk for neurological and intellectual impairments that occur at the time of school age. These impairments may include cerebral palsy, mental retardation, autism, low intelligence, and learning problems.
Abnormal labor (i.e., abnormal fetal positions) can create critical pressure on the skull and other complications, e.g., anoxia which can cause damage to brain tissue. |
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185. Postnatal (acquired) issues that can cause mental retardation
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1. Infection, (e.g, among the most serious are encephalitis, and meningitis)
2. Head trauma, (e.g., caused by vehicular accidents, household accidents, or seizures) |
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186. Angelman syndrome
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Deletion in part of chromosome 15 of maternal origin
Fair hair and blue eyes (66%); dysmorphic faces including wide smiling mouth, thin upper lip, and pointed chin; epilepsy (90%) with characteristic EEG; ataxia; small head circumference, 25% microcephalic Happy disposition, paroxysmal laughter, hand flapping, clapping; profound mental retardation; sleep disturbance with nighttime waking; possible increased incidence of autistic features; anecdotal love of water and music |
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187. Cornelia de Lange syndrome
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Lack of pregnancy associated plasma protein A (PAPPA) linked to chromosome 9q33;
Continuous eyebrows, thin downturning upper lip, microcephaly, short stature, small hands and feet, small upturned nose, anteverted nostrils, malformed upper limbs, failure to thrive Self-injury, limited speech in severe cases, language delays, avoidance of being held, stereotypic movements, twirling, severe to profound mental retardation |
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188. Williams syndrome
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1/20,000 births; hemizygous deletion that includes elastin locus chromosome 7q; autosomal dominant
Short stature, unusual facial features including broad forehead, depressed nasal bridge, stellate pattern of the iris, widely spaced teeth, and full lips; elfinlike facies; renal and cardiovascular abnormalities; thyroid abnormalities; hypercalcemia Anxiety, hyperactivity, fears, outgoing, sociable, verbal skills > visual spatial skills |
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189. Smith-Magenis syndrome
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Incidence unknown, estimated 1/25,000 live births; complete or partial deletion of 17p11.2
Broad face; flat midface; short, broad hands; small toes; hoarse, deep voice Severe mental retardation; hyperactivity; severe self-injury including hand biting, head banging, and pulling out finger- and toenails; stereotyped self-hugging; attention seeking; aggression; sleep disturbance (decreased REM) |
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190. Rubinstein-Taybi syndrome
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1/250,000, approx. male = female; sporadic; likely autosomal dominant
Short stature and microcephaly, broad thumb and big toes, prominent nose, broad nasal bridge, hypertelorism, ptosis, frequent fractures, feeding difficulties in infancy, congenital heart disease, EEG abnormalities, seizures Poor concentration, distractible, expressive language difficulties, performance IQ > verbal IQ; |
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191. Xrays, CTs, MRIs and EEGs in dx of mental retardation
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Skull X-rays are usually taken routinely, but are illuminating in only a relatively few conditions, such as craniosynostosis, hydrocephalus, and other disorders that result in intracranial calcifications
Computed tomography (CT) scans and magnetic resonance imaging (MRI) have become important tools for uncovering CNS pathology associated with mental retardation An EEG is best interpreted with caution in cases of mental retardation. |
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192. Mental retardation and pervasive developmental disorders
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Mental retardation and pervasive developmental disorders often coexist; 70 to 75 percent of those with pervasive developmental disorders have an IQ below 70.
A pervasive developmental disorder results in distortion of the timing, rate, and sequence of many basic psychological functions necessary for social development. Because of their general level of functioning, children with pervasive developmental disorders have more problems with social relatedness and more deviant language than those with mental retardation. In mental retardation, generalized delays in development are present, and mentally retarded children behave in some ways as though they were passing through an earlier normal developmental stage, rather than one with completely aberrant behavior. |
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193. Age and diagnostic criteria for mental retardation and dementia
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Children under the age of 18 years who meet the diagnostic criteria for dementia and who have an IQ below 70 are given the diagnoses of dementia and mental retardation.
Those whose IQs drop below 70 after the age of 18 years and who have new onsets of cognitive disorders are not given the diagnosis of mental retardation but only the diagnosis of dementia. |
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194. Primary prevention in mental retardation
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a. Socialize the community to the strengths and abilities of the mentally retarded, and not focusing on the disabilities.
B. legislative and social supports are to be encouraged to create necessary protections so the mentally retarded can function independently as possible in society to the best of their respective capabilities |
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195. Secondary and tertiary prevention in mental retardation
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Includes medical treatments to with intervening and rectify metabolic and endocrine disorders. E.g., PKU and hypothyroidism, can be maintained by diet control and /or hormonal replacement therapy
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196. Goals of education in mentally retarded
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a. adaptive skills training
b. vocational training c. communication skills |
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197. Behavioral therapy and mentally retarded
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Behavioral therapy will shape and enhance social behaviors, as well as to teach ways in which the individual can learn to minimize aggressive urges and destructive behaviors
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198. Family education in those families with mentally retarded
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Family Education will assist the individuals, perhaps largest and most immediate support system, to maintain realistic expectations of the mentally retarded, and to maintain a balance between independence and where needed supervision
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199. Normalization
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“Normalization” a concept that grew out of the 1970’s focuses on
ways to make the mentally retarded functional members of the community by: a. making available to the mentally retarded conditions of every day life that are as close as possible to the norms and patterns of the mainstreamed society b. having no institutionalized mentally retarded children c. have special educational classes within a regular school setting so that there can be some inclusive interaction |
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200. Ritalin vs. Risperidone in treatment of ADHD
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Although risperidone has been shown to be associated with significant symptom reduction of hyperactivity and disruptive behavior, and in general, adverse events during a year of treatment were mild, given its side effect profile compared with methylphenidate, it is still prudent to begin with a trial of a stimulant medication before the use of antipsychotic prepeparations for the treatment of ADHD.
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201. Treatment of agression and self-injurious behavior
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Some evidence from controlled and uncontrolled studies indicates that lithium (Eskalith) has been useful in decreasing aggression and self-injurious behavior. Narcotic antagonists such as naltrexone have not been systematically shown to diminish aggression or self-injurious behaviors.
Anticonvulsants, such as carbamazepine (Tegretol) and valproic acid (Depakene), have been used clinically for aggressive behavior in children and adolescents |
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202. Mental retarded and risk of tardive dyskinesia
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Persons with mental retardation appear to be at higher risk for the development of tardive dyskinesia after use of a variety of antipsychotic medications.
The atypical antipsychotics, including risperidone and clozapine (Clozaril), may provide some relief with a decreased risk of tardive dyskinesia. |
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203. Treatment of stereotypical motor movements in the mentally retarded
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Serotonin reuptake inhibitors, such as fluoxetine, fluvoxamine (Luvox), paroxetine, and sertraline, have been shown to have efficacy in treating obsessive-compulsive symptoms in children and adolescents and, thus, may have some efficacy for stereotyped motor movements.
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204. Treatment for explosive rage behavior in the mentally retarded
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β-Adrenergic receptor antagonists (beta-blockers), such as propranolol (Inderal), reportedly result in fewer explosive rages in patients with mental retardation and autistic disorder. Antipsychotic medications have also been used in the treatment of explosive rage. Systematic controlled studies are indicated to confirm the efficacy of these drugs in the treatment of rage outbursts.
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