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101 Cards in this Set
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- Back
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Orotic Aciduria |
Can't make UMP (de novo pyrimidine synthesis) - 1) Orotic acid in urine; 2) Failure to thrive; 3) Megaloblastic anemia; 4) NO HYPERAMMONEMIA (as in OTC deficiency) - Tx: oral uridine administration |
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Adenosine Deaminase Deficiency |
Problem with de novo purine synthesis - 1) SCID; 2) Low lymphocyte count - Tx = gene therapy for the bubble boy |
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Lesch-Nyhan syndrome |
Problem w/ de novo purine synthesis - 1) MR; 2) Self-mutiliation (violent tendencies); 3) Choreoathetosis; 4) Hyperurecemia w/ gout! - Tx: Allopurinol to lower uric acid levels |
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I-cell disease |
Lysosomal enzymes not tagged with 6-MP and end up outside the cell, frequently fatal in childhood - 1) Cloudy cornea; 2) Coarse facial features; 3) Restricted joint movement; 4) High plasma levels of lysosomal enzymes |
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Chediak-Higashi Syndrome |
Microtubule polymerization defect so phagosome lysosome fusion defect - 1) Recurrent pyogenic ingections; 2) Partial albinism; 3) peripheral neuropathy |
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Kartagener's syndrome |
Immotile cilia problem - 1) male and female infertility; 2) Bronchiectasis; 3) Recurrent sinusitis; 4) Associated with situs inversus |
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Osteogenesis Imperfecta |
Type 1 collagen defect - 1/10,000 prevalence - type I seen but type II fatal in utero - 1) Brittle bones; 2) Blue sclera; 3) Abnormal dentin/ teech; 4) Abnormal hearing (middle ear bones) |
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Ehlers-Danlos |
Type 3 collagen defect (usually) - 1) Hyperextensible skin that is smooth and potentially painful to the touch; 2) Easy bruising; 3) Berry aneurysms; 4) Easy joint dislocation/ hypermobile joints; 5) Risk of organ ruptures |
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Alport Syndrome |
Type IV collagen defect - 1) Hereditary nephritis; 2) Deafness (tympanic membrane); 3) Lenticonus (thinning of lens) causing ocular disturbance |
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Marfan's Syndrome |
Autosomal Dominant
Fibrillin gene mutation leading to abnormal elastin - 1) Tall stature; 2) Long limbs and fingers/ toes (arachnodactyly); 3) Pectus excavatum; 4) Aneurysm risk due to cystic medial necrosis of the aorta - can lead to aortic incompetence and dissecting aortic aneurysms; 5) Floppy mitral valve; 6) Berry aneurysms; 7) Lens subluxation risk; |
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Emphysema |
Alpha 1 - antitrypsin deficiency so uninhibited elastase so lose elasticity - if primary, also will have cirrhosis due to misfolded protein accumulation in liver (young non-smoker) |
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Prader-Willi syndrome |
Paternal gene on chromosome 15 is deleted (or maternal disomy) - 1) MR; 2) Short stature; 3) Hyperphagia; 4) Obesity; 5) Hypotonia; 6) Hypogonadism - Dx: FISH - Tx: GH to increase stature + keep food away |
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Angelman's Syndrome |
Maternal gene on chromosom 15 deleted (or paternal disomy) - "Happy puppet" - 1) MR; 2) Inappropriate laughter; 3) Propensity for seizures; 4) Ataxia - Don't confuse with Williams because these people don't look like elves - Dx: FISH |
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Achondroplasia |
Autosomal Dominant FGF receptor 3 defect - 1) Dwarfism with short limbs but normal head and trunk size - RF: Advanced Paternal Age |
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Autosomal-dominant polycistic kidney disease (ADPKD) |
Adult with bilateral massive enlargement of kindeys w/ cysts due to PKD1 mutation (90%) on chromosome 16 - 1) Flank pain; 2) Hematuria; 3) HTN; 4) Progressive renal failure - Associations = 1) Polycystic liver disease; 2) Berry aneurysms!; 3) Mitral valve prolapse
Infantile form is recessive |
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Familial Adenomatous Polyposis |
Autosomal Dominant Colon covered w/ adenomatous polyps after puberty and leading to colon cancer unless resected due to mutations on chromosome 5 (APC gene)
Associated with Gardner's disease... also get osteomas, lipomas |
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Familial Hypercholesterolemia (Hyperlipidemia type IIA) |
Autosomal Dominant- Due to absent or devective LDL receptor (elevated LDL cholesterol)
Homozygotes (rare) --> cholesterol = 700+ mg/dL Heterozygotes (1:500) --> cholesterol = 300 mg/dL Normal: 140-250 mg/dL
Severe atherosclerotic disease early in life, tendon xanthomas (Achilles), MI may develop before age 20 |
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Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) |
Autosomal Dominant - Inherited disorder of blood vessels
Tetrad: Telangiectasia (dilated capillaries), recurrent epistaxis, skin discolorations, AVMs (arteries and veins connected with capillary bypass) |
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Hereditary Spherocytosis |
Autosomal Dominant Spheroid erythrocytes due to spectrin or ankyrin defect Labs: Increased MCHC (mean corpuscular Hb concentration - Hb concentration in a given packed RBC volume)
Sx: Hemolytic anemia, jaundice, splenomegaly
Dx: Osmotic fragility test (place in hypotonic solution and look for relatively quick hemolysis) Tx: Splenectomy is curative! |
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Huntington's disease |
Autosomal Dominant Due to chromosome 4 CAG repeat (exhibits anticipation as do most trinucleotide repeat problems)
Findings: manifestation of these in person between 20-50 y/o 1) Choreiform movements; 2) Caudate atrophy; 3) Depression; 4) Progressive dementia
Labs: GABA and ACh decrease in brain |
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Multiple Endocrine Neoplasias |
Autosomal Dominant
1, 2a, 2b - discussed in endocrine section |
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NFT 1 |
Autosomal Dominant Chromosome 17 long arm problem 1) Cafe-au-lait spots; 2) Lisch nodules (pigmented iris hamartomas due to dendritic melanocyte accumulation); 3) Neural tumors (i.e.: optic pathway glioma); 4) Often conjoined w/ skeletal problems such as scoliosis - These adults get those skin tumors |
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NFT 2 |
Autosomal Dominant Chromosome 22
1) Acoustic neuroma/ schwannoma; 2) Juvenile cataracts |
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Tuberous Sclerosis |
Autosomal Dominant
1) Facial lesions (adenoma sebaceum - hypopigmented ash-leaf spots); 2) cortical and retinal hamartomas; 3) Seizures; 4) MR; 5) Renal cysts and *angiomyolipomas*; 6) *Cardiac rhabdomyomas*; 7) *Increased incidence of astrocytomas*
Variable penetration with incomplete penetrance! |
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von Hippel-Lindau disease |
Autosomal Dominant Chromosome 3p (VHL gene deletion - tumor supressor) leading to constitutive HIG (transcription factor) and activation of angiogenic growth factors
1) Hemangioblastomas of retina/ cerebellum/ medulla; 2) 1/2 will develop multiple bilateral renal cell carcinomas! |
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Cystic Fibrosis |
Autosomal Recessive Chromosome 7 - CFTR degene defect where CFTR channel normally actively secretes Cl- in lungs and GI tract and actively reabsorbs Cl- from sweat - but this channel is defective (where Cl goes, Na and water follow)
1) Secretion of abnormally thick mucus that plugs lungs, pancreas, and liver; 2) Recurrent pulmonary infections that culture positive of Pseudomonas; 3) Pancreatic insufficiency (malabsorption and steatorrhea); 4) Nasal polyps; 5) Meconium ileus in newborns; 6) Infertility in males due to bilateral absense of vas deverens!; 7) Fat-soluble vitamin deficiences (A,D,E,K); 8) failure to thrive in infancy
Most common lethal genetic disease of caucasians
Dx: Sweat Cl- > 60meq/L Tx: N-acetylcysteine to loosen mucuous plugs (cleaves disulfide bonds within mucous glycoproteins) + will be on antibiotics all the time to maintain good lung hygeine; pancreatic enzyme supplemenation; supplement fat soluble vitamins |
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Duchenne's Muscular Dystrophy |
X-linked frame-shift mutation leading to dystrophin gene deletion (dystrophin helps anchor muscle fibers) which causes accelerated muscle breakdown w/ onset before the age of 5
1) Weakness begins in pelvic girdle muscles and progresses superiorly; 2) Pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle; 3) Cardiac myopathy; 4) Use of Gower's maneuver (use his hands and arms to "walk" up his own body from a squatting position due to lack of hip and thigh muscle strength)
Dx: Increased CPK and muscle biopsy showing fibrofatty replacement |
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Becker's Muscular Dystrophy |
X-linked mutated dystrophin gene (no frameshit) - Less severe than Duchenne's; Onset in adolescence or early adulthood |
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Fragile X Syndrome |
X-linked CGG trinucleotide repreat disorder affecting FMR1 gene (the second most common cause of genetic MR after Down syndrome)
1) Macro-orchidism (enlarged testes); 2) Long face with a large jaw; 3) Large everted ears; 4) Autism; 5) Mitral valve prolapse |
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Down Syndrome (trisomy 21) |
1:700 - Most common cause of congenital MR Associated w/ advanced maternal age Mother <20 (1:1500) Mother >45 (1:25)
Pregnancy Quad Screen: Low AFP and estriol; High beta hcg and Inhibin A
Ultrasound: shows nuchal translucency (due to fluid accumulation around the neck - also in Turner's)
1) Flac facies; 2) prominent epicanthal folds; 3) simian crease (single transverse palmar crease); 4) Gap between 1st 2 toes; 5) Duodenal atresions (closure); 6) Congenital heart disease (most commonly septum primum - type ASD); 7) Increased risk of ALL and AML and ALzheimer's disease (>35 y/o); 8) 65% have polycythemia |
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Edwards' syndrome (trisomy 18) |
1:8,000 Death usually occurs within 1 year of birth
Quad screen: Low AFP, beta hcg and estriol; Normal Inhibin A
1) Severe MR; 2) Rocker-bottom feet; 3) Micrognathia (small jaw); 4) Low-set ears; 5) Clenched hands; 6) Prominent occiput; 7) Congenital heart disease
Most common trisomy resulting in live birth after down syndrome |
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Patau's syndrome (trisomy 13) |
1:15,000 Death usually occurs within 1 year of birth
Quad screen: Normal AFP, beta hcg, inhibin A and estriol
1) Severe MR; 2) Rocker bottom feet; 3) Microphthalmia; 4) Microcephaly; 5)*Cleft lip/palate; 6)*Holoprosencephaly (single midbrain eye); 7) *Polydactyly; 8) Congenital heart disease |
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Cri-du-chat syndrome |
"Cry of the cat" Congenital microdeletion of the short arm of chromosome 5
1) Microcephaly; moderate to sever MR; 3) *High-pitched crying/ mewing; 4) Epicanthal folds; 5) Cardiac abnormalities (VSD) |
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Williams Syndrome |
Congenital microdeletion of long arm of chromosome 7 (including the elastin gene)
1) "Elfin syndrome (how to distinguish from Angelman's syndrome); 2) Extreme friendliness with strangers; 3) MR; 4) Hypercalcemia (increased sensitivity to vitamin D); 5) Well-developed verbal skills; 6) Cardiovascular problems (valvular defects) |
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22q11 deletion syndromes |
22q11 deletion
DiGeorge syndrome or Velocardiofacial syndrome due to aberrant development of 3rd and 4th branchial pouches
Variable presentation (CATCH-22): 1) Cleft palate; 2) Abnormal facies; 3) Thymic aplasia (T-cell deficiency); 4) Cardiac defects; 5) Hypocalcemia secondary to parathyroid aplasia due to microdeletion at chromosome 22q11 |
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Vitamin A (retinol) deficiency |
1) Night blindness (vit A = constituent of visual pigments); 2) Dry skin (vit A = essential for normal differentiation of epithelial cells into specialized tissue); 3) xeropthalmis (don't produce tears); 4) Wrinkling; 5) Corneal clouding; 6) Bitot's spots (dry gray keratin plaques on conjuntiva); 7) Corneal ulcers |
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Vitamin A (retinol) excess |
Polar bear liver
Pregnancy test MUST be performed before isotretinoin is prescribed for severe acne
1) Arthralgias; 2) Fatigue; 3) *H/A (pseudotumor cerebri - elevated intracranial pressure in the absence of a tumor w/ elevated CSF pressure!); 4) Sore throat; 5) Alopecia; 6) Hypercalcemia; 7) Teratogenic (cleft palate and cardiac abnormalities by inhibiting neural crest cell migration) |
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Vitamin B1 (thiamine) deficiency |
Wernicke_Korsakoff syndrome and BeriBeri (Ber1Ber1) - Seen in malnutrition as well as alcoholism (secondary malnutrition and malabsorption) - in places where "polished" rice is part of diet
Impaired glucose breakdown affecting highly aerobic tissues first (brain & heart)
WK: Confusion, opthalmoplegia (paralysis of ocular muscle), ataxia, confabulation (can't remember what you just asked), personality change, antegrade memory loss (permanent), damage to medial dorsal nucleus of thalamus and mammillary bodies
Dry beriberi: non-specific with polyneuritis (inflammation of several peripheral nerves), symmertrical muscle wasting, foot drop, wrist drop, hyporeflexia, areflexia
Wet beriberi: high-output cardiac failure (dilated cardiomyopathy), peripheral vasodilation, edema |
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Vitamin B2 (riboflavin) deficiency |
Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth), Corneal vascularization, Dermatitis, Glossitis (smooth pink/purple tongue) |
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Vitamin B3 (niacin) deficiency |
Derived from tryptophan - can lead to pellagra which can be casued by Hartnup disease (low tryptophan absorption), malignant carcinoid syndrom (increased tryptophan metabolism), and isoniazid (INH - lower vitamin B6)
Seen in corn eating population (they lack tryptophan)
The 3 D's: Dermatitis, Diarrhea, Dementia - also GLOSSITIS |
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Vitamin B3 (niacin) excess |
Facial flushing (due to pharmacologic doses for hyperlipidemia treatment) |
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Vitamin B5 (pantothenate) deficiency |
Essential component of CoA
Dermatitis, enteritis, alopecia, adrenal insufficiency (no true disease state) |
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Vitamin B6 (pyridoxine) deficiency |
Convulsions (because you can't make GABA); hyperirritabiilty; peripheral neuropathy; sideroblastic anemias (due to impaired Hb synthesis and Fe excess)
Deficiency inducible by INH and OCP |
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Biotin deficiency |
Causes: avidin in egg white prevents abosrption, abx use
Relatively rare - dermatitis, alopecia, enteritis |
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Vitamin B12 (cobalamin) deficiency |
Deficiency is usually caused by malabsorption (sprue, enteritis, Diphyllobothrium latum), lack of intrinsic factor (pernicious anemia, gastric bypass surgery), or absence of terminal ileum (Crohn's disease)
Dx: Schilling test: 1) normal; 2) Add intrinsic factor; 3) Add pancreatic enzymes; 4) Add abx
Tx: Oral B12 w/ intaact IF and ileum; IM injxn of cyanocobalamin for all the other Pxs
1) Megaloblastic anemia; 2) Hypersegmented PMNs; 3) Neurologic symptoms (paresthesias, subacute combined degeneration) due to abnormal myelin - Prolong deficiency leads to irreversible nervous sytem damage; 4) Homocystinuria |
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Folic Acid (vitamin B9) deficiency |
Macrocytic, megaloblastic anemia; NO NEUROLOGIC SYMPTOMS (as opposed to B12 deficiency) - Most common vitamin deficiency in the us! Seen in alcoholism and pregnancy and certain drugs (i.e.: phenytoin, sulfonamids, MTX)- Neural tube defects; megaloblastic anemia; growth failure
Supplemental folic acid in early pregnancy reduces neural tube defects
Pregnant women --> need .4 mg of folic acid Excess of folate --> aggravates B12 deficiency (because B12 us used to make THF) Too little B12 --> deficiency in THF |
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Vitamin C (ascorbic acid) deficiency |
3 main fxns: NE; collagen; iron absorption
Scurvy - swollen gums, brusiing, hemarthrosis, anemia, poor wound healing - weakened immune response
Labs: Low NE with high Dopamine |
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Vitamin C (ascorbic acid) excess |
N/V, diarrhea, fatigue, sleep problems - can increase risk of iron toxicity in predisposed individuals (i.e.: those with transfusions, hereditary hemochromatosis) |
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Vitamin D deficiency |
Vit D increases the intestinal absorption of calcium and phosphate; also increases bone mineralization - 25-OH D3 = storage form; 1,25-OH(2)D3 calcitriol = active form
Rickets in children (bending bones); Osteomalacia in adults (soft bones); Hypocalcemic tetany! - Breast milk has low vitamin D; Supplement in dark-skinned patients
Labs: low calcium and phosphate
1) Excess unmineralized bone matrix; 2) Bow-legged; 3) lumbar lordosis; 4) protrustion of sternum and ribs; 5) overgrowth of cartilage at costochondral junction |
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Vitamin D excess |
Hypercalcemia, hypercalciuria, loss of appetit, stupor - Seen in sarcoidosis (increased activation of vitamin D by epithelioid macrophages) |
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Vitamin E (alpha tocopherol) decifiency |
Hereditary form = gene mutation in alpha tocopherol transfer gene protein
Increased erythrocyte fragility (hemolytic anemia); muscle weakness; posterior columb and spinocerebellar tract demyelination (ataxia, loss of proprioception _ hemolytic anemia NOT megaloblastic anemia... how to differentiate from vitamin B12 deficiency) |
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Vitamin K deficiency |
Newbord should get single IM injxn of vitamin K at birth till bacteria line gut
Neonatal hemorrhage with increased PT and PTT but normal bleeding time (platelets not affected) - neonates have sterile intestines and are unable to synthesis vitamin K - can also occur after prolonged use of broad spectum antibiotics
1) Jaundice; 2) hemolysis |
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Zinc deficiency |
Delayed wound healing; may predispose to alcohol cirrhosis; rash around eyes, mouth, nose, and anus (acrodermatitis enteropathica); hypogonadism; lower adult hair (axillary, facial, pubic); dysgeusia; anosmia; impaired night fision; infertility; poor immune response! |
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Mercury Poisoning |
Accumulates in kidney and brain
Recently near shark, swordfish, old thermometers, batteries
Gas state = more problematic
Acrodynia = peeling of finger tips (also seen in Kawasaki disease) |
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Arsenic Poisoning |
Garlic breath with rice water stool (inhibits pyruvate dehdrogenase)
Common in Bangladeshi water; Increases cancer risk of all tissues especially the skin |
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Cadmium Poisoning |
Impacst mostly lungs but also kidneys and bone (osteomalacia)
Causes obstructive lung disease via alveolar macrophage destruction; increases lung cancer risk |
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Methanol or Ethylene Glycol poisoning |
Tx: Fomepizole (alcohol dehydrogenase blocker) to prevent toxic intermediates although ethanol is favored (competitive inhibition) |
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Alcoholism |
Tx: Disulfiram (Antabuse) inhibits acetaldehyde dehydrogenase to increase hangover symptoms |
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Kwashiorkor |
Clinical pix = small child with swollen belly
Protein malnutrition resulting in skin lesions, edema, liver malfunction (fatty change due to low apolipoprotein synthesis - fat can't leave without apo-B100) |
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Marasmus |
Energy malnutrition resulting in tissue and muscle wasting; loss of subcutaneous fat; and variable edema |
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Refeeding Syndrome |
Occurs when you haven't had anything to eat for ~5 days
Severe arrythmias due to ion imbalance |
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Pyruvate dehydrogenase deficiency |
1) Neurologic defects
Tx: increase intake of ketogenic nutrients (i.e.: high fat content or increase lysince and leucine)
Mech: Backup causes lactic acidosis which can be congenital or acquired (as in alcoholics due to B1 deficiency) |
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G6PDH (glucose-6 phosphate dehydrogenase) deficiency |
X-lined recessive
Dx: Heinz bodies (oxidized precipitated Hb); Bite cells (due to phagocytic removal of heinz bodies by splenic macrophages)
Low NADPH leads to *hemolytic anemia* (free radical damage) particularly in the presence of oxidizing agents (i.e.: fava beans, sulfonamides, primaquine, antituberculosis drugs or INFECTION because free radicals generated in inflammator response)
Increases malarial resistance so more common among black population! |
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Essential fructosuria |
Autosomal recessive
Sx: Fructose appears in blood and urine (doesn't enter cells) because it does not enter cells in liver (site of fructose metabolism) |
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Fructose intolerance |
Autosomal recessive
Sx: Hyoglycemia, jaundice, cirrhosis, vomiting
Tx: Lower intake of both fructose and sucrose (glucose + fructose)
Hereditary deficiency of aldolase B enzymes ultimately leading to inhibition of glycogenolysis and gluconeogenesis (due to phosphate depletion) - recall fructose metabolism occurs in liver |
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Galactokinase deficiency |
AR
Sx: 1) Galactose appears in glood and urine; 2) Infantile cataracts (galacitol); 3) May initially present as failure to track objects or to develop a social smile (infants) - Relatively mild condition!
Tx: Minimize galactose in diet |
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Classic galactosemia |
Sx: Failure to thrive; jaundice; hepatomegaly; infantile cataracts; MR
Tx: Exclude galactose and lactose (galactose + glucose) from diet
Mech: Accumulation of toxic substances (including galacitol) due to absent galactose-1-phosphate uridyltransferase |
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Sorbital related tissue damage |
Hyperglycemia may send glucose down a pathway where body converts it to sorbitol and then fructose. Enzyme for second reaction (sorbitol deydrogenase) is missing in some tissues leading to the proglems of hyperglycemia...
Sx: Cataracts (len); retinopathy (retina); peripheral neuropathy (schwann cells); kidneys |
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Lactase deficiency/ Lactose intolerance |
Sx: Bloating, cramps, osmotic diarrhea if lactose consumed + flatulence (sugar draws water in intestines)
Tx: Avoid dairy products or add lactase (lactaid) pills to diet
Age-dependent and/or hereditary lactose intolerance due to loss of brush-border enzyme lactase. May also follow gastroenteritis (temporary and self-resolving)
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Hyperammonemia |
Sx: Tremor, slurring of speech, somnolence, comiting, cerebral edema, blurring of vision - **HEPATOENCEPHALOPATHY**
Tx: Limit protein in diet; *Benzoate or *Phenylbutyrate (both bind to amino acid and lead to excretion) can help lower ammonia levels in short term; *Lactulose can acidify the GI and trap NH4+ for excretion |
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OTC (Ornithine transcarbamoylase) deficiency |
X-linked recessive
Sx: Orotic acid in blood and urin, low BUN, plus symptoms of hyperammonemia (hepatoencephalopathy) which is how to distinguish from orotic aciduria - Often evident in first few days of life but may present with late onset - excess carbamoyl phosphate is converted to orotic acid |
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Phenylketonuria |
AR - 1:10,000
Sx: MR, growth retardation, seizures, fair skin, eczema, musty/ mousy body odor***
Screening: for 2-3 days after birth (normal at birth because of maternal enzyme during fetal life)
Mech: Due to phenylalanine hydroxylase deficiency or decreased tetrahydrobiopterin cofactor (malignant phenylketonuria)
Tx: Lower phenylalanine (contained in aspartame, i.e.: NutraSweet) and increase tyrosine in diet; possibly tetrahydrobiopterin supplementation |
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Maternal PKU |
Cause: Lack of proper dietary therapy during pregnancy
Findings in infant: Microcephaly, MR, growth retardation, congenital heart defects
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Alkaptonuria (ochronosis) |
AR
Sx: Benign disease (assuming no debilitating arthralgias - homogentisic acid toxic to cartilage); dark connective tissue; brown pigmented sclera; urine turns black on prolonged exposure to air
Mech: homogentisic acid oxidase deficiency (congenital) |
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Albinism |
Sx: lack of melanin results in an increased risk of cancer)
Mech: 1) Tyrosinase deficiency; 2) Tyrosine transporter defect; 3) Neural crest cell migration defect |
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Homocystinuria |
Sx: Dramatic increase in homocysteine in urine, MR, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), and atherosclerosis (stroke and MI) - Cysteine becomes essential
Tx 1: Cystathionine synthase deficiency (lower Methionine, increase cysteine, and increase vitamin B12 and folate)
Tx 2: Low affinity of cystathionine synthase for pyridoxal phosphate (increase vitamin B6 in diet!)
Tx 3: Homocysteine methyltransferase deficiency (tx not written) |
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Cystinuria |
AR - 1:7,000
Tx: Acetazolamide (carbonic anhydride crystal) to alkanize the urine
Sx: Excess cysteine in urine can lead to the precipitation of cysteine kidney stones (staghorn calculi)
Mech: Hereditary defect of renal tubular amino acid transporter for amino acids in proximal convoluted tubule |
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Maple syrup urine disease |
Sx: severe CNS defects, MR, death, and urine that smells like maple syrup/ burnt sugar
Lab: Increase alpha-ketoacids in blood especially Leucine
Mech: Blocked branched amino acid degradation due to low alpha-ketoacid dehdyrogenase |
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Hartnup disease |
AR
Sx: Tryptophan excretion in urine and low tryptophan absorption from the gut leading to symptoms of pellagra!!! (b3) - Pellagra --> Dermatitis, diarrhea, dementia, death!
Mech: Defective neutral amino acid transporter on renal and intestinal epithelial cells |
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Von Gierke's disease (glycogen storage disorder type I) |
Sx: Severe fasting hypoglycemia; HIGH glycogen levels in liver; high blood lactate levels; enlarged kidneys; hepatomegaly |
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Pompe's disease (glycogen storage disorder type II) |
Sx: Cardiomegaly and systemic findings leading to early death ("Pompe's trashes the pump - heart, liver, and muscle") |
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Cori's disease (glycogen storage disorder type III) |
Sx: Milder form of type I w/ normal blood lactate levels, no hypoglycemia, and too much glycogen
Gluconeogenesis is intact! |
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McArdle's disease (glycogen storage disorder type IV) |
Sx: Increase glycogen in muscle, but can't break it down, leading to painful muscle cramps and myoglobuinuria with strenuous exercise (muscle degradation)
M = muscle |
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Fabry's Disease |
Sx: Renal disease; Cardiovascular disease; Angiokeratomas; peripheral neuropathy of hands/ feet
Lysosomal storage disorder - sphingolipidoses |
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Gaucher's disease |
Most common lysosomal storage disorder!! (sphingolipidoses)
Sx: hepatosplenomegaly; Aseptic necrosis of femur; Bone crises; Gaucher's cells (macrophages that look like crumpled tissue paper) |
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Niemann-Pick disease |
Sx: death by age 3 but have cherry-red spot on macular; hepatosplenomegaly; progressive neurodegenerations; and foam cells
Lysosomal storage disorder - sphingolipidoses |
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Tay-Sachs disease |
Sx: death by age 3; but cherry-red spot on macula with NO hepatosplenomegaly (vs. Niemann-Pick); lysosomes with onion skin; developmental delay; progressive neurodegeneration
Lysosomal storage disorder - sphingolipidoses |
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Krabbe's disease |
Sx: Death by age 3; optic atrophy; globoid cells; developmental delay; peripheral neuropathy
Lysosomal storage disorder - sphingolipidoses |
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Metachromatic leukodystrophy |
Sx: Central and peripheral demyelination with ataxia; dementia
Lysosomal storage disorder - sphingolipidoses |
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Hurler's syndrome |
Sx: Corneal clouding with hepatosplenomegaly; gargoylism (coarse facial features); airway obstruction; development delay
Lysosomal storage disorder - mucopolysaccharidoses |
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Hunter's syndrome |
Sx: Mild Hurler's + aggressive behavior, no corneal clouding w/ MR (Hunter's see clearly)
Lysosomal storage disorder - mucopolysaccharidoses |
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Scheie syndrome |
Sx: Mild Hurler's with corneal clouding, facial dysmorphism, and normal lifespan
Lysosomal storage disorder - mucopolysaccharidoses |
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I-Cell |
Sx: Corneal clouding + MR; particularly severe form of ML that has a significant resemblance to another mucopolysaccharidoses called Hurler syndrome. Generally only laboratory testing can distinguish the two as the presentation is so similar. Typically, by the age of 6 months, failure to thrive and developmental delays are obvious symptoms of this disorder.
Lysosomal storage disorder - mucopolysaccharidoses |
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Early Starvation (24 hours) |
Goal: Supply sufficient glucose to the brain and RBCs and to preserve protein!
Glucose from fluconeogenesis Fatty acids from adipose tissue Brain uses glucose Muscles and other tissues use some glucose but predominantly fatty acids RBCs can ONLY use glucose |
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Intermediate Starvation (2 days) |
Glucose from gluconeogenesis FA from adipocytes ***Ketone bodies from liver*** Brain usese flucose and some ketone bodies Muscles and other = fatty acids mostly and some ketone bodies RBCs can ONLY use glucose |
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Prolonged Starvation (5 days) |
Glucose from gluconeogenesis Fatty acid from adipose tissue Ketone bodies from liver Brain uses ketone bodies predominantly Muscles and other tissues use fatty acids and ketone bodies |
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Diabetic ketoacidosis (mechanism) |
Prolonged starvation leads to stalling of TCA cycle which shunts glucose and FFA toward the production of ketone bodies
Sx: breath smells like acetone (Fruity odor) Urine: Test for ketones |
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Type I Familial Dyslipidemia/ Hyper-chylomicronemia |
Increased: Chylomicrons; Riskfactor for hypertiglyceridemia and acute pancreatitis
Potential Sx: pancreatitis, hepatosplenomagealy, eruptive/ pruritic xanthomas (no increased risk for atherosclerosis)
Labs: Elevated TG (increases risk of pancreatitis), cholesterol
Mech: Lipoprotein lipase deficiency or altered apolipoprotein C-II (LPL cofactor) |
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Type IIa Familial Dyslipedemia/ Hypercholesterolemia |
Sx: Accelerated atherosclerosis, tendon (achilles) xanthomas, & corneal arcus (opaque ring in corneal circle); MI at young age
Labs: Elevated Cholesterol & LDL
Mech: Absent or reduced LDL receptors |
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Type IV Familial Dyslipedemia/ Hyper-triglyceridemia |
Sx: Acute pancreatitis
Labs: TG increase
Increased: VLDL
Mech: Hepatic overproduction of VLDL |
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Abetalipoproteinemia |
Sx: Symptoms appear in the first few months of life - Failure to thrive; steatorrhea; acanthocytosis (spiky RBCs); ataxia; night blindness
Bx: Shows accumulation within enterocytes due to inability to export absorbed lipid as chylomicrons
Tx: Vitamin E is helpful |
