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67 Cards in this Set
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Muscular Dystrophy |
Includes Duchenne and Becker muscular dystrophies, X-linked mutations. Skeletal muscle breakdown, muscle weakness/wasting, decreased motor skills, inability to walk. Caused by the absence or mutation of the protein dystrophin, which provides strength for skeletal muscle cells by anchoring the internal cell components to the extracellular matrix. Example of protein-protein interactions involving hydrophobic and hydrophilic interactions. Book p9 |
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Osteogenesis imperfecta |
Genetic disease that affects collagen-containing tissues such as bone, skin, joints, eyes, ears, and teeth, because of point mutations that destabilize or alter collagen's triple helix structure. Results in frequent fractures and easy bruising, weak joints, bluish color to white part of eyes, hearing loss due in part to abnormalities of the inner ear bones, and poorly shaped small blue-yellow teeth. Collagen is a triple helix that utilizes hydrogen bonding between the 3 helices. In each helix, collagen has Gly-X-Y, where X and Y are any other AA but most commonly Pro or hydroxyproline. Book p10 |
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Kartagener Syndrome |
aka Primary Ciliary Dyskinesia. Defective cilia in the respiratory tract, Eustachian tube, and Fallopian tubes, leading to chronic lung infections, ear infections and hearing loss, and infertility. Possible association with "situs inversus," a condition in which major internal organs are flipped left to right. Book p12 |
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Senior-Loken Syndrome |
aka Nephronophthisis. One type of ciliopathy. Eye disease and formation of cysts in the kidneys leading to renal failure. |
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Bardet-Biedl Syndrome |
Disfunction of cilia throughout the body leading to obesity due to inability to sense satiation, loss of eye pigment/visual loss and/or blindness, extra digits and/or webbing of fingers and toes, mental and growth retardation and behavioral/social problems, small and/or misshaped genitalia (M or F), enlarged and damaged heart muscle, and kidney failure. |
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Alstrom Syndrome |
One type of ciliopathy. Childhood obesity, breakdown of the retina leading to blindness, hearing loss, and type II diabetes. |
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Ciliopathies |
Defects in cilia, flagella, or microtubules; encompasses at least 8 diseases/syndromes |
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Meckel-Gruber Syndrome |
One type of ciliopathy. Formation of cysts in kidneys and brain leading to renal failure and neurological deficits, extra digits and bowing/shortening of the limbs.e |
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Increased Ectopic (Tubal) Pregnancies / Male Infertility |
One type of ciliopathy. Deficient cilia in Fallopian tubes or deficient flagella/sperm tail motility |
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Autosomal Recessive Polycystic Kidney Disease |
One type of ciliopathy. Much rarer than the autosomal dominant form, dysfunction of basal bodies and cilia in renal cells leads to alternations of the lungs and kidneys leading to a variety of secondary medial conditions and often death. |
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Parkinson's and Alzheimer's diseases |
One type of ciliopathy. Some forms of PD and AD may result, in part, from damage to microtubules and associated proteins. |
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Abinism (oculocutaneous albinism) Type 1 |
Deficit in tyrosinase, the first enzyme in the melanin synthetic pathway. Variations exist. Patients can have no, some, or even temp-dependent pigment formation. Affects predom. Amish/Mennonite peoples. |
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Albinism (oculocutaneous albinism) Type 2 |
Most common type of albinism. Defect in the p-protein, which regulates melanocyte pH and affects pigment production. Patients have some pigment production (i.e., moles freckles) and fewer vision problems. |
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Gout |
medical condition typified by excessive amounts of uric acid in the body; results in formation of uric acid crystals that become lodged in soft tissues, joints resulting in severe "gouty arthritis" pain. |
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Lesch-Nyhan syndrome |
Genetic disease of excessive synthesis of purines because of defective recycling, causing uric acid production from the breakdown of purines. Characterized by gouty arthritis, mental retardation, loss of arm/leg/face movement control, aggressive behavior, self mutilation. Affects almost solely males. |
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Adenosine Deaminase Deficiency |
Deficiency in adenosine deaminase causes deficiency in breakdown of nucleotides and nucleosides. Results in severe combined immunodeficiency syndromes. |
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Phenylketonuria (PKU) |
Genetic disease (autosomal recessive, affects 1/15000 births) caused by the deficiency of phenylalanine hydroxyls, required to convert Phe to Tyr. Results in low Tyr and increased levels of phenylketones, due to increased conc of Phe. Causes traits of albinism, phenyl acetate odor in sweat. If not treated, results in brain damage, seizures. Treated by diet low in Phe. |
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Albinism (oculocutaneous albinism) Type 3 |
Defect in tyrosine-related protein-1 (TRP-1), involved in melanin synthesis but also possibly affecting and regulating tyrosinase activity and melanocyte proliferation and death. Results in reddish hair, red-brown skin, blue-grey eyes. |
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Albinism (oculocutaneous albinism) Type 4 |
Defect in membrane-associated transporter protein (MATP), regulating melanin synthesis and melanocyte differentiation. Usu found only in Japan and in a small German population. Patients have white to yellow to brown hair, light blue-gray to brown eyes, and visual problems. |
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Albinism (general). aka oculocutaneous albinism |
There are at least 4 variations Type 1-4. All impact the production of the pigment melanin. Affects hair and skin pigments, as well as vision to varying degrees. No cure available; treatment is supportive. FYI variations that only affect the eyes (ocular albinism) are all X-linked. |
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Alkaptonuria (aka black urine disease) |
-Defect in the gene for homogentisic acid oxidase. Breakdown of Phe and Tyr is inhibited, leading to increased conc of the intermediate alkapton. Excessive alkapton is excreted in urine and turns into a brown-black melanin-like color when exposed to air. -Causes urine color change, higher incidence of kidney and prostate stones, deposition of homogentisic acid in cartilage (joint damage), coronary artery disease, pigment deposit in skin. -First inherited disease involving a metabolism error that was characterized (1859). |
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Glycine encephalopathy |
-Defect in mitochondrial Gly cleavage enzyme system responsible for Gly degradation. A defect in any of the proteins in this system (p-protein, H-protein, T-protein, or L-protein) leads to increased Gly in blood, urine, CSF. -Presents in 3 forms: Neonatal, Infantile, or Atypical mild form. All result in mental retardation, muscle and nerve symptoms, and seizures. Neonatal form can cause death. |
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Histidinemia |
-Defective histidine ammonia-lyase, rqrd for removal of an amino gp during His degradation. -Results in high levels of histidine, histamine, and imidazole in urine, blood, CSF. Usu clinically insignificant but may lead to developmental disorders in neonates, infants, and sm children. -The most common disorder in persons of Japanese descent. |
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Wilson's disease |
Caused by excess copper ion concentrations in liver, brain, eyes, and other tissues. Results from low activity of ATPase, Cu-transporting, beta polypeptide (ATP7B), responsible for copper transport out of cells. Liver deposits can cause liver failure and cancer; Brain deposits can lead to seizures, psychosis, parkinsons tremors. Deposition in eyes results in the diagnostic "Kayser-Fleischer ring" a brownish-green ring evident in the cornea. |
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Menke's "kinky hair" disease |
very rare, X-linked recessive. Mutation in ATPase, Cu-transporting, alpha polypeptide (ATP7A). Causes growth failure and retardation, abnormal body temp, weak bones, sparse, course, fragile kinky, colorless hair. |
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Homocystinuria |
-Defect in cystathionine beta-synthase, rqrd for conversion of homocystein to cytathionine, part of the breakdown pathway of methionine. -Defect results in accumulation of homocysteine in blood/urine, excessively long limbs and fingers, dislocation of lens of eye, mental problems, vein/artery blockage and stroke. -Treated with high doses of vitB6, normal dose folic acid/cysteine/trimethylglycine, or decrease in methionine in diet. |
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Hypervalinemia |
-Defect in valine transaminase, resulting in increased levels of valine in blood/urine. -Presents in infants with poor appetite and feeding, poor growth and weight gain, drowsiness, diarrhea and vomiting, dehydration, mental retardation -Treated with diet restriction of valine. |
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Isovaleric acidemia (aka sweaty feet disease) |
-Defect in the enzyme isovaleryl coenzyme A dehydrogenase, which is responsible for the 3rd step in the degradation of leucine. -Deficiency results in increased levels of isovaleric acid in blood/urine, which is toxic to CNS. -Acute (fatal) form occurs in newborns: acidification of blood, convulsions, decreased platelets and WBC, and an unusual urinary odor like sweaty feet, rapid death. Chronic intermittent (nonfatal) form results in periodic attacks of acidification of blood possibly resolving by glycine detoxification pathway. -treated with reduction of leucine in diet and administration of glycine to help remove toxic isovaleric acid. -Hallmark sweaty feet odor results from increased butyric and hexanoic acids from unrelated but possibly linked error in FA metabolism. |
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Glucose-6-phosphate dehydrogenase deficiency (G6PDH) |
-Most commonly inherited enzyme disorder in the world (affects 25%), X-linked; over 400 variants. -Defects in G6PDH (first step of pentose phosphate pathway). Absence of pentose phosphate pathway limits the availability of NAD phosphate, therefore reduced glutathione. Reduced glutathione is the only protection for RBCs against oxidation by free radicals. -patients often asymptomatic, but acute episodes of hemolysis can occur to due infection, medications, or foods. |
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Ketotic hyperglycinemia (aka propionic acidemia) |
-Defect in proprionyl-CoA carboxylase, essential for breakdown of propionyl-CoA, a product of the metabolism of several AAs (val, ile, thr, met) and the oxidation of odd-numbered FAs. -Leads to increased gly, proprionyl-CoA, propionic acid, ketones, ammonia, and acid level in blood/urine. Presents in infants with brain/heart/liver damage, vomiting, fatigue, low/absent neutrophils and/or platelets and/or blood protein, poor tolerance of dietary protein. May have frequent infections due to a decrease in white blood cells. -Treated by careful restriction of dietary protein. -Propiony-CoA with oxaloacetate also forms methyl citrate, which inhibits the TCA cycle. |
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Maple syrup urine disease (aka branched-chain aminoaciduria) |
-Deficit of branched-chain alpha leto acid dehydrogenase complex (3 enzyme subunits), rqrd for oxidative decarboxylation of the alpha ketoacids produced by the removal of the amino gp during degradation of branched-chain AAs (leucine, isoleucine, and valine). Ketoacidosis results from the branched-chain alpha ketoacid accumulation. Urine has a characteristic maple syrup odor. -Newborns are listless, have feeding difficulties, seizures, abdominal pain, interrupted breathing, developmental delay. Can cause death in first months of life. -Treatment includes restricting dietary intake of branched-chain AAs in formula and vit B1. Early treatment can prevent neurological damage. -Common in certain Mennonite populations. |
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Methylmalonic acidemia (MMA) |
-Defect in methylmalonyl-coA mutase, responsible for the breakdown of branched-chain AAs and methionine. This enzyme is also involved in lipid and cholesterol metabolism and requires vit B12, so B12 deficiencies can cause the same disease state. -Leads to the inability to metabolize certain AAs and lipids/cholesterol. Patients present with nausea/vomiting, dehydration, poor growth, hypotonia, lethargy. Can cause mental deficits, kidney/liver/pancreatic disease, coma/death. -Treatment includes restriction of dietary proteins replaced by simple carbs to limit metabolism, restriction of affected AAs and supplementation of B12. |
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3-phosphoglycerate dehydrogenase deficiency |
-Defect in 3-phosphoglycerate dehydrogenase, the enzyme responsible for the first step in the synthesis of serine. Serine is major source of 1-C gps for purine nucleotides -deficiency leads to severe neurological consequences, including a severely undersized brain (congenital microcephaly). Diagnosis can be made by measuring Ser and Gly levels in plasma and CSF. -Treatment is by supplementation with Ser and Gly. |
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Phosphoserine amino-transferase deficiency |
-Defect in phosphoserine aminotransferase, the 2nd enzyme in serene biosynthetic pathway. Deficiency in Ser results in similar clinical manifestations as noted for 3-phosphoglycerate dehydrogenase deficiency, including microcephaly, neurological defects, seizures, abnormal posture and muscle tone. Diagnosis is made by low Ser/Gly levels in plasma and CSF. -Treatment is by supplementation with Ser and Gly. |
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Smith-Magenis Syndrome (SMS) |
Defect in Ser hydroxymethyltransferase, leading to decreased or absent conversion of Ser to Gly. Exact mechanism unknown, but association with the NMDA receptor involved in learning and memory as well as glycine's role in transmission of nerve signals may explain disease symptoms. -patients have facial abnormalities, abnormality in sleep cycles, display the unique characteristic of repetitive self-hugging and "lick and flip" activity -No cure. Treatment is supportive, focused on controlling symptoms and supplementation and regulation of melatonin, sleep aids, and behavioral modifiers. |
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Type I tyrosinemia (tyrosinosis) |
Defect in fumarylacetoacetase, the enzyme required for the last step in Tyr degradation. Results in buildup of all intermediates of Tyr degradation as well as Phe byproducts. -symptoms occur in early months, poor growth, cabbage-like odor, intestinal bleeding, kidney and pancreatic failure, rickets. -Treated with diet low in Phe, Met, and Tyr. Liver transplant is common. |
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Type II tyrosinemia |
Defect in tyrosine transaminase, required for the first step in Tyr degradation. Leads to urinary excretion of Tyr and the intermediates btw Phe and Tyr. -Symtoms usually in early childhood including mental retardation, slow growth, eye and skin problems (excessive tears, painful lesions on palms/soles). -Treated with low-protein diet, esp decreased Tyr and Phe. |
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Type III tyrosinemia |
Deficit of 4-hydroxy phenylpyruvate dioxygenase, rqrd for second step in Tyr degradation. Leads to elevated levels of Tyr in blood and marked excretion of degradation byproducts into urine. -Mild retardation, periodic loss of balance, seizures. -Treated with low-protein diet, esp decreased Tyr and Phe. VERY RARE. |
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Cystinuria |
AA transport disease -Defect in the AA transporter for basic or pos. charged AAs (His, Lys, Orn, Arg, Cys), leading to a defect in the transport of these AAs in the kidney and digestive tract. -Results in precipitation of cystine and the formation of stones in the urinary tract. Can lead to urinary infections and kidney failure. -Treatment directed at prevention of stones through high fluid intake and the use of penicillamine. -One of the most common (1/7000) original inborn errors of metabolism (discovered in 1908) |
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Drummond's Syndrome (blue diaper syndrome) |
AA transport disease -Defect in T-type AA transporter-1, rqrd for absorption of Trp from intestine. May also lead to increased urine Ca+ levels and kidney stones composed of Ca+. -Digestive problems, fever, kidney disease. Breakdown of excess Trp leads to formation of indigo blue excreted in urine, causing a bluish discoloration of the diaper. -Treated with low Trp diet. -Autosomal or X-linked recessive. |
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Hartnup disease (neutral aminoaciduria) |
AA transport disease -Defect in Na+ dependent transport protein for uncharged AAs in the kidneys and intestine, resulting in poor absorption and increased loss of uncharged AAs in the urine (many of which are essential). Also causes low nicotinamide. -Symptoms usu start in infancy, affecting brain and skin, failure to thrive, sun sensitivity, mental retardation, psychiatric changes possible. -Treated with diet high in AAs, sunblock and/or sun avoidance, nicotinamide. |
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Hyperammonemia-hyperornithinemia-homocitrullinuria (HHH syndrome) |
AA transport disease -Defect in the mitochondrial ornithine transporter. Results in ammonia accumulation in blood. -Symptoms vary widely. Infantile form is usu more sever, with lethargy, poor feeding and temp control, coma, death. May coincide with introduction of high-protein formulas or solid foods. Later forms include lethargy, confusion, blurred vision, poor coordination, vomiting. |
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Methionine maladsorption syndrome (Smith-Strang disease/Oasthouse urine disease) |
AA transport disease -Defect in the protein(s) essential for intestinal absorption of methionine (and other AAs). Unabsorbed methionine is converted by intestinal bacteria to the chemical alpha-hydroxybutyric acid, which produces a urine odor of an oasthouse (a building for drying hops). -Strikingly white hair and blue eyes, increased breathing rate, diarrhea, seizures, mental retardation, characteristic urine odor. -extremely rare, no established treatment but dietary restriction of methionine is implied. |
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Arginase deficiency (argininemia) |
Urea Cycle disorder -Defect in arginase, the 5th and final enzyme of the urea cycle, which removes N from Arg to produce a urea molecule. Also increases guanidine metabolites, which contribute to toxicity. -Deficit blocks the urea cycle and leads to incr conc of ammonia in blood. Poor feeding and growth, development and mental retardation, seizures, coma, possibly death. -Treated with low protein diet balanced with AA supplementation to all urea cycle to continue. Phenylacetate may be given to help remove accumulated glutamine via the kidneys. Liver transplant sometimes rqrd. |
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Arginosuccinate synthetase (ASS) deficiency (citrullinemia, types I and II) |
Urea Cycle disorder -Defective ASS, the enzyme involved in the 3rd step in the urea cycle that synthesizes argininosuccinate from citrulline and Asp. Mutation decreases prod of citrin, a mitochondrial Asp/Glu carrier. Deficiency affects molecules that are involved in the urea cycle and synth of proteins and nucleotides. -Type I patients have increased levels of ammonia in blood, which leads to sever symptoms (above) in first few days of life. -Type II: adult. Buildup of ammonia impacts nervous system, causing confusion and personality problems, seizures. Sometimes triggered by alcohol use -Treatment is same as Arg deficiency (low protein diet, AA supplementation, phenyl acetate) |
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Argininosuccinic aciduria/acidemia |
Urea Cycle disorder -Defect in argininosuccinate lyase, the 4th enzyme of the urea cycle that cleaves argininosuccinate into arg and fumarate. -Symptoms and treatment same as arginase deficiency and all urea cycle disorders. |
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carbamoyl phosphate synthetase I (CPS-1) deficiency |
Urea Cycle disorder -Defecit in CPS1, the enzyme responsible for the first reaction of the urea cycle: transfer of ammonia to bicarb to produce carbamate using one ATP. -Symptoms and treatment same as arginase deficiency and same as all urea cycle disorders |
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N-acetylglutamate synthase (NAGS) deficiency |
Urea Cycle disorder -Deficit in NAGS, the enzyme responsible for the production of N-acetylglutamate from acetyl-CoA and Glutamate. -Symptoms and treatment same as arginase deficiency and all urea cycle disorders. |
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Ornithine transcarbamylase (OTC) deficiency |
THE MOST COMMON Urea Cycle disorder -Deficit of OTC, the 2nd urea cycle enzyme, producing citrulline from carbamoyl phosphate and ornithine. -Symptoms and treatment same as arginase deficiency and all urea cycle disorders. |
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alpha-1-antitrypsin (AAT) protease inhibitor deficiency |
Structural protein disorder -The defective anti-elastase causes degradation of extracellular fibrils such as elastin with gradual loss of pulmonary function. Lungs and liver are especially damaged by progressive proteolytic damage. -long time association of AAT deficiency with emphysema. Smoking causes oxidation of the methionine residue in the AAT molecule, which limits it binding to serene protease and further reduces its inactivation function. -treated with IV concentrates of AAT combined with avoiding smoking. |
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Ehlers-Danlos syndrome (EDS), (cutis hyperelastica) |
Structural protein disorder -Defects involving collagen; multiple mutations -EDS-affected collagen causes easy bruising and wounds with pigmented scarring, overly flexible joints, heart valve defects, uterine and bowel rupture, and/or gum problems. -no cure. treatment is supportive for cardiovascular and internal organs. corrective surgery sometimes undertaken. |
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Cutis laxa |
Structural protein disorders -Group of related disorders with varying inheritance patterns: Dominant = defects in elastin/fibulin, Recessive = defects in fibulin, X-linked (occipital horn syndrome) = defects in Cu-transporting ATPase, alpha polypeptide. -skin elasticity is disrupted, wrinkled, hangs loose. Severe disease can involve the structure of internal organs, hernias, easy bruising, low copper, bone outgrowths from the back of head (in x-linked) -treatment is supportive, no cure. |
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Marfan syndrome |
Structural protein disorder -defect in the extracellular glycoprotein fibrillin, which affects cysteine-rich, tertiary structural domains. -mutations in fibrillin weaken connective tissue structure and disrupt binding to TGF-beta protein. Adversely affects structure of smooth muscle and extracell matrix, esp in lungs, blood vessels, heart valves. -no cure. monitoring only. sometimes use of beta blockers and angiotensin II receptor blockers to reduce TGF-beta and control cardiovascular manifestations. |
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Fructosuria (hepatic fructokinase deficiency) |
Carbohydrate defect -Defect in liver fructokinase, which metabolizes the first step in fructose metabolism (fructose to fruc-1-P) -Often asymptomatic, although episodes of hypoglycemia (low sugar), nausea/vomiting, seizures, and unconsciousness can occur, esp in children. -Treatments is by avoidance of fructose in diet with replacement by glucose sources. |
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Classic galactosemia (galactosemia I) |
Carbohydrate defect -Deficiency of galactose-1-phosphate uridyl transferase, which catalyzes the interconversion of galactose-1-P and glucose-1-P via transfer of uridine monophosphate. -Mech still not clear, but detrimental effects thought to be due to accum of galactose and gal-1-P. Patients develop cataracts, hepatomegaly, speech and learning problems, sometimes mental retardation. -Treated by avoidance of galactose and lactose in diet. But since gal is generated by other pathways, some effects are likely inevitable. -Galactosemia may also affect inositol metabolism and therefore essential signaling pathways. |
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Galactokinase deficiency (galactosemia II) |
Carbohydrate defect -Deficiency of galactokinase enzyme, which catalyzes the first step in gal metabolism, the phosphorylation of gal to gal-1-P. -Cataracts (due to incr osmotic pressure caused by accum of gal-derived molecules) in the lens. Possible mental retardation. -Treated by avoidance of dietary gal and lactose. If gal-free diet is started early, cataracts will regress without complications, but neurological damage is permanent. |
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Galactose epimerase deficiency (galactosemia III) |
Carbohydrate defect -Deficiency of the UDP-galactose-4-epimerase, which catalyzes the final step of gal metabolism, involving the interconversion of UDP-gal and UDP-glu. -Increase in gal and gal-1-P levels (similar to other galactosemias). Symptoms are sim to type I/II, including cataracts; also includes poor growth, nerve deafness, liver/kidney failure. -Treated as with type I/II (avoidance of gal and lac in diet). -Both a mild form (affecting RBCs) and a sever form (affecting the liver) exist. |
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Hereditary fructose intolerance (aldolase B deficiency) |
Carbohydrate defect -Defect in fruc-1-6-bisphosphate aldolase b enzyme, responsible for the conversion during glycolysis of fruc-1-6-bisP to glyceraldehyde-3-P and dihydroxyacetone-P. Also involved in gluconeogenesis. -Deficit leads to increase in fruc-1-P levels, which is damaging to cells and tissues and traps PO4 from normal regerating pathways. Decreased P/ATP causes decrease in liver gluconeogenesis and low glucose levels, can be fatal. Low glucose and ATP also leads to lowered protein synth, liver and kidney function, causing nausea/vomiting and abdominal pain -Treated by complete avoidance of fructose, sucrose, and sorbitol in the diet. Alternative carbohydrates can be metabolized by other tissues to provide body's needs. |
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Hyperglycerolemia (glycerol kinase deficiency) |
Carbohydrate defect -Deficiency of glycerol kinase enzyme, which catalyzes the phosphorylation of glycerol by ATP to ADP and glycerol-3-P. -exists in 3 forms: infantile, juvenile and adult. Infantile form has severe developmental delays, vomiting, and seizures. Other forms usually asymptomatic. -treatment is via a low-fat diet, which can provide dramatic improvement in symptoms/development. -FYI elevated levels of glycerol in the blood and urine can be mistaken for triglycerides. |
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Pyruvate kinase deficiency |
Carbohydrate defect -Deficiency of the RBC pyruvate kinase enzyme, which is the last run of the glycolytic pathway, catalyzes the conversion to PEP to pyruvate with the formation of ATP. -RBCs cannot produce energy without pyruvate kinase, so they breakdown easily, leading to hemolytic anemia. Symptoms are pale skin, jaundice, yellowing of the white of the eyes, fatigue, and recurrent bilirubin gall stones. -Bl transfusions can treat anemia, and removal of spleen slows the breakdown of RBCs. Severe untreated cases cause death as early as neonatal period. |
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Glycogen storage disease (GSD; type O) (liver glycogen synthase deficiency) |
-Deficiency of liver glycogen synthase that catalyzes the addition of glucose units to glycogen via transfer from uridine diphosphate glucose -patients present in infancy or early childhood with hypoglycemia and blood ketones. Often present with morning fatigue that responds to feeding. Fasting may cause low blood alanine and lactate. Dietary glucose cannot be readily stored as glycogen, leading to hyperglycemia and even lactic acid after meals. -avoid fasting. must receive frequent feedings of protein-rich meals. Avoid excess carbohydrate intake that would exacerbate lacticacidemia. Lack of treatment can lead to short stature and oseopenia. Neurological damage may occur because of dependency of NS tissue on glucose as fuel. -Once pancreatic amylase activity is high enough, raw cornstarch can be given at night (pancreatic amylase acts on it slowly over 6 hrs) |
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Gycogen storage disease (GSD; type Ia) (Von Gierke disease) |
-Deficiency of glucose-6-phospatase that catalyzes the conversion of G6P to glucose in the liver and kidney. -Presents in infants with hepatomegaly that may develop into benign liver cancer (adenoma), usu in the teen years. Liver/pacreas effects and kidney stones. Hypoglycemia can lead to seizures, death; high uric acid can lead to gouty arthritis; hyperuricemia; Dyslipidemia is very common with high triglycerides, VLDL, LDL, and cholesterol. Elevated lipid manifest as xanthomas. -Diet must be closely monitored to balance blood glucose and hepatic glycogen stores. Avoid high fat/cholesterol foods due to hyperlipidemia |
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Glycogen storage disease (GSD; type II) (Pompe disease) |
-Deficiency of the acid maltase (a-glucosidase) enzyme that degrades glycogen to glucose in lysosomes. -Excessive glycogen accumulates in the body but esp in the heart. Symptoms in infancy include poor weight gain. Lung infection completes respiratory problems and heart is enlarged. Both can lead to death. -Requires a specialist team to monitor treatment. Enzyme replacement therapy has been developed (Alglucosidase-alpha drug is approved). |
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Glycogen storage disease (GSD; type III) (Cori or Forbes disease) |
-Deficiency of the glycogen debrancher enzyme that is responsible for moving three glucose residues from a branch of four glucose residues to the end of a longer chain. -Diagnosed in infancy or early childhood. Characteristic hepatomegaly and hypoglycemia, and possible ketoacidosis. Muscle involvement leads to low muscle tone, hypotonia and muscle wasting in adults. Also cardiomyopathy and polycystic ovaries. -Patients need to avoid hyperglycemia, but it's not as severe as type I. High protein diet provides AA for gluconeogenesis. |
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Glycogen storage disease (GSD; type IV) (Andersen disease; amylopectinosis) |
-Deficiency of the glycogen branching enzyme that catalyzes the addition of a glucose residue as a branch to a glucose chain of glycogen -No muscle symptoms. Patients begin as poor feeders and develop severe disease and hepatomegaly that can lead to terminal liver failure and scarring (cirrhosis) by age 5. Liver damage leads to portal hypertension resulting in esophageal varicose, encephalopathy, spleen enlargement, and diminished renal function. Liver biopsy shows excessive accumulation of glycogen. -Treatment options are minimal. Diet therapy is only partly successful. Liver transplant. |
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Glycogen storage disease (GSD; type V) (McArdle disease) (Hers disease) |
-Deficiency of the liver glycogen phosphorylase isoform that catalyzes the removal of glucose residues from glycogen to form Glu-1-P -Presents at age 1-5yrs. Hepatomegaly and growth retardation. Mild symptoms of hypoglycemia, high lipids and blood ketones. -Dietary restrictions are sufficient, and disease conditions improve with age. |
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Glycogen storage disease (GSD; type VII) (Tarui disease) |
-Deficiency of the muscle phosphofructokinase (PFK) that catalyzes the glycolytic conversion of Fruc-6-P to fruc-1,6-bisP (3rd rxn of glycolytic pathway) -Although deficiency is in glycolysis, this is considered a GSD because of the inability to use glycogen-derived glucose for fuel. Glycogen accumulates in the muscle and Glu6P enters the pentose P pathway generating excess ribose for nucleotide synth. Excess nucleotides degrade to uric acid, causing gout. Also get myoglobinuria with strenuous exercise. -No specific treatment needed, except avoidance of high-carb diet. Also avoid vigorous exercise to prevent myoglobinuria. |
