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6. FA Biochem Path

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Ehlers-Danlos syndrome
Symptoms: Weak epithelium...skin and blood vessels. Hyperextensible skin, tendency to bleed, easy bruising, hypermobile joints. Increased risk of Berry aneurysms, joint dislocation. Lab Values: Pathophysiology: Defect in type I or V collagen. Treatment:
Alport's syndrome
Symptoms: Progressive hereditary nephritis, deafness, and ocular distrubances. Lab Values: Pathophysiology: X-linked recessive. Defect in type IV collagen leading to defective basement membranes. Treatment:
Marfan's syndrome
Symptoms: {{Tall with long extremities}}, {{pectus excavatum}}, hyperextensive joints, and long, tapering fingers and toes (arachnodactyly), {{mitral prolapse}}. cystic medial necrosis of aorta leading to {{aortic insufficiency}} and {{dissecting aortic aneurysms}}; . Subluxation of lenses and retinal detachment. Lab Values: Pathophysiology: Defect in fibrillin 1 affecting skeleton, heart, and eyes. Fibrillin is part of elastic tissue structure. Chromosome 15. Treatment:
Prader-Willi syndrome
Symptoms: Mental retardation, {{hyperphagia, obesity}}, {{hypogonadism}}, hypotonia. Lab Values: Pathophysiology: Due to deletion of normally active {{paternal}} allele (chromosome 15), materal uniparental disomy, or imprinting (methylation). Treatment:
Angelman's syndrome
Symptoms: Mental retardation, {{seizures, ataxia, inappropriate laughter ("happy puppet")}}. Lab Values: Pathophysiology: Due to deletion of normally active {{maternal}} allele (chromosome 15), paternal uniparental disomy, or imprinting (methylation). Treatment:
Cystic fibrosis
Symptoms: Absence of vas deferns (infertility). Pancreatic insufficiency leading to ADEK vitamin deficiency. Bronchiectasis, recurrent pulmonary infections (Pseudomonas and S. aureus). Failure to pass meconium. Lab Values: Increased chloride ions in sweat. More negative transepithelial membrane potential (in mild CF); increased sodium absorption. Pathophysiology: Autosomal recessive. Defect in CFTR gene on chromosome 7. Mutation causes abnormal protein folding, resulting in degradation of channel before reaching cell surface. CFTR normally secretes chloride in lungs and resorbs chloride from sweat. Treatment: N-acetylcysteine
Duchenne's muscular dystrophy
Symptoms: Gower's sign (weakness of pelvic muscles). {{Pseudohypertrophy of calf muscles}} (fibrofatty infiltrates). Accelerated muscle breakdown. Lab Values: Diagnoise by {{increased creatine phosphokinase (CPK)}} and muscle biopsy. Pathophysiology: X-linked recessive. {{Frameshift mutation in Dystrophin (DMD) gene, an anchoring protein for sarcomeres.}} Treatment:
Becker's muscular dystrophy
Symptoms: Milder form of Duchenne's. Lab Values: Pathophysiology: X-linked recessive. {{Missense}}, not a frameshift mutation. Treatment:
Fragile X syndrome
Symptoms: {{Mental retardation}} (second most common genetic cause), {{Congenitial giant gonnads!!}}, long face, large ears, autism, {{mitral valve prolapse}}. Lab Values: Pathophysiology: Hypermethylation of FMR1 gene. {{Trinucleotide repeat disorder (CGG).}} Treatment:
Down's syndrome
Symptoms: Mental retardation (most common genetic cause), flat facies, prominent epicanthal folds, simian crease, umbilical herniation, hypotonia, duodenal atresia, gat between 1st 2 toes, septum primum ASD / VSD / {{endocardial cushion defect}} / mitral regurgitation. {{Increased risk of ALL/AML and early onset Alzheimer's disease}}. Lab Values: Decreased {{A-fetal protein}}, estriol. {{Increased beta-hCG, inhibin A}}. Increased nuchal translucency on ultrasound. Pathophysiology: {{Trisomy 21}}. Can be caused by meiotic nondysjunction (most common), t(14;21) Robertsonian translocation, Down mosaicism (mitotic nondysjunction). Treatment:
Edward's syndrome
Symptoms: Severe mental retardation, {{rockerbottom feet (big heel with a high arch)}}, {{micrognathia (small jaw)}},{{low-set ears...small jaw pulls the ears down}}, {{clenched hands (finger overlap)}}, prominent occiput, c[[ongenital heart disease}}. Death usually occurs within 1 year of birth. Lab Values: Pathophysiology: {{Trisomy 18}} Treatment:
Patau's syndrome
Symptoms: Severe mental retardation, {{rocker-bottom feet}}, {{microphthalmia}}, microcephaly, {{cleft lip/palate...doesn't fuse}}, {{holoprosencephaly...doesn't split}} (two brain hemispheres do not seperate), polydactyly, congenital heart disease. Death usually occurs within 1 year of birth. Lab Values: Pathophysiology: Trisomy 13 Treatment:
Cri-du-chat syndrome
Symptoms: Microcephaly, moderate to severe mental retardation, {{high-pitched crying/mewing}}, epicanthal folds, cardiac abnormalities. Lab Values: Pathophysiology: {{5p deletion.}} Treatment:
Williams syndrome
Symptoms: {{"Elfin" facies}}, mental retardation, {{well-developed verbal skills, extreme friendliness with strangers}}, cardiovascular problems. Lab Values: {{Hypercalcemia}} (increased sensitivity to vitamin D). Pathophysiology: {{7q deletion}} (including elastin gene). Treatment:
Hirschsprung's disease
Symptoms: Presents as {{chronic constipation early in life}}. Dilated portion of the colon proximal to the aganglionic segment, resulting in a "transition zone." Involves rectum. Usually failure to pass meconium. Lab Values: Pathophysiology: Congenital megacolon characterized by lack of ganglion cells/enteric nervous plexuses (Auerbach's and Meissner's plexuses) in segment on intestinal biopsy..{{no nerves..no peristalsis}}. {{Due to failure of neural crest cell migration.}} Multifactorial inheritance, associated with {{Trisomy 21}}. Treatment:
Turner's syndrome
Symptoms: {{Coarctation of the aorta, cystic hygroma (webbed neck)}}, short stature, low hair line, bicuspid aortic valve, {{ovarian dysgenesis (streak ovaries)}} Lab Values: {{No Barr bodies}}. {{Decreased estrogen, elevated LH and FSH.}} Pathophysiology: 45, {{XO}}. Treatment:
Klinefelter's syndrome
Symptoms: {{"Boy that looks has a lot of girl features..."}} Testicular atrophy, eunuchoid body shape, tall, long extremities, gynecomastia, female hair distribution. May present with developmental delay. Lab Values: {{Presence of Barr body}}. Low inhibin, high FSH. Low testosterone, high LH, high estrogen. Pathophysiology: {{46, XXY}}. Treatment:
Myotonic dystrophy
Symptoms: {{Difficulty releasing doorknob or releasing grip (myotonia; sustained contractions)}}, {{frontal baldness}}, gonadal atrophy, cataracts, {{heart block}}. Lab Values: Pathophysiology: Autosomal dominant. Trinucleotide repeat disorder (CTG)...{{Can't Turn loose Grip}} {{Atrophy of type I fibers on biospy.}} {{Defective myotonia-protein kinase}}. Treatment:
Xeroderma pigmentosum
Symptoms: Increased sensitivity to UV radiation and increased of cutaneous malignancy. Lab Values: {{Increased thymidine dimers}}. Pathophysiology: Autosomal recessive. {{Defect in DNA excision repair (UV-endonuclease)}}. Treatment:
Fanconi's anemia
Symptoms: {{aplastic anemia}}. {{Hypoplastic bone anomalies...stiff bones}} Increased MDS and AML risk. Associated with polydactylyl, microcephaly, hypogonadism. Lab Values: Pathophysiology: Autosomal recessive. Hypersensitivity to DNA cross-linking agents (cyclophosmamide); Treatment:
Bloom's syndrome
Symptoms: Hypersensitivty to UV damage and chemotherapeutic (cross-linking?) agents. Lab Values: Pathophysiology: Autosomal recessive. Treatment:
HNPCC
Symptoms: Lab Values: Pathophysiology: Defect in DNA mismatch repair. Treatment:
Adenosine deaminase deficiency
Symptoms: Severe combined immunodeficiency. Lab Values: Pathophysiology: Adenosine deaminase is used in purine salvage (adenosine turnover). Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide and prevents DNA synthesis and thus decreases lymphocyte count. Treatment: Gene therapy.
Lesch-Nyhan syndrome
Symptoms: Retardation, {{self-mutilation, aggression, hyperuricemia, gout}}, choreoathetosis. Lab Values: Hyperuricemia. Pathophysiology: X-linked recessive. {{Defect in HGPRT}} resulting in {{excess uric acid production. Failure of purine salvage pathway}}. Treatment:
I-cell disease
Symptoms: Coarse facial features, {{clouded corneas, restricted joint movement,}} high plasma levels of lysosomal enzymes. Fatal in childhood. Lab Values: {{Lysosomal enzymes secreted outside the cell; ghost lysosomes.}} Pathophysiology: Lysosomal storage disease; {{failure of mannose-6-phosphate addition}} which is required to traffic proteins to lyosomes. Treatment:
Kartagener's syndrome
Symptoms: {{Situs inversus}} (organs are flipped), {{infertility}}, bronchiectasis, {{recurrent sinusitis}}. Lab Values: Pathophysiology: {{Defect in dynein arm that leads to immotile cilia}}. Bacteria and particles not pushed out of lungs. Treatment:
Vitamin A deficiency
Symptoms: {{Night blindness}}, dry skin, squamous metaplasia of duct linings, {{follicular hyperkeratinosis...blocks hair follicles ->allopecia}}. Lab Values: Pathophysiology: Caused by dietary deficiency or malabsorption (pancreatitis, cystic fibrosis, sprue, mineral oil intake). Antioxidant; constituent of visual pigments (retinal); {{essential for normal differentiation of epithelial cells into specialized tissue}} (pancreatic cells, mucus-secreting cells). Treatment:
Vitamin A excess
Symptoms: {{Angular cheilitis}} (ulcers/lesions at angle of lips), {{elevated ICP}} (papilledema...optic disk swelling), arthralgia, fatigue, headaches, skin changes, sore throat, alopecia. {{Teratogenic (cleft palate, cardiac abnormalities)}}. Must do pregnancy test before isoretinoin prescribed for acne. Lab Values: Pathophysiology: {{Eating liver, leafy vegetables}}. Treatment:
Vitamin B1 (thiamine) deficiency
Symptoms: {{Wernicke-Korsakoff syndrome}} (Drunk...confusion, opthalmoplegia, ataxia, memory loss, confabulation, personality changes). {{Dry beriberi}} (polyneuritis, symmetrical muscle wasting). {{Wet beriberi}} (high-output cardiac failure / dilated cardiomyopathy, edema). Lab Values: Pathophysiology: Seen in {{alcoholics}} and malnutrition. {{B1 is a component of dehydrogenase and transketolase}}. {{Leads to impaired glucose breakdown and ATP depletion}}; {{highly aerobic tissues (brain and heart) affected first}}. DON'T INFUSE GLUCOSE (exacerbates thiamine deficiency.) Treatment:
Vitamin B2 (riboflavin) deficiency
Symptoms: {{Magenta colored tongue...FLAVOR}}, {{cheilosis}} (inflammation of lips, scaling and fissures at corners of mouth), {{corneal vascularization.}} Lab Values: Pathophysiology: {{Cofactor in oxidation and reduction (FADH2)}}. Treatment:
Vitamin B3 (niacin) deficiency
Symptoms: {{Glossitis}}. Severe defiicency leads to {{pellagra}} (dermetitis, diarrhea, dementia). Can be caused by Hartnup disease (decreased tryptophan absorption), malignant carcinoid syndrome (increase trytophan metabolism), and isoniazid (decrease Vit B6). Lab Values: Pathophysiology: Component of NADP+ and NAD+. {{Derived from tryptophan. Synthesis requires B6...so any defect in tryptophan or B6 access}}. Found it corn but not absorable unless treated. Treatment:
Vitamin B3 (niacin) excess
Symptoms: Facial flushing (due to pharmacological doses for treatment of hyperlipidemia). Lab Values: Pathophysiology: Treatment:
Vitamin B5 (pantothenate) deficiency
Symptoms: Dermatitis, enteritis, alopecia, adrenal insufficiency. Lab Values: Pathophysiology: {{Essential component of CoA and fatty acid synthase}}. Treatment:
Vitamin B6 (pyridoxine) defiency
Symptoms: {{Convulsions}}, {{hyperirritability}}, {{peripheral neuropathy}}, and {{sideroblastic anemia}}. Deficiency induced by isoniazid, oral contraceptives. Lab Values: Pathophysiology: {{Required for transaminations (ALT/AST)}}, decarboxylation reactions, glycogen phosphrylase, cystathionine synthesis, and heme synthesis. Required for synthesis of niacin for tryptophan. Treatment:
Vitamin B12 (cobalamin) deficiency
Symptoms: {{Megaloblastic anemia, hypersegmented PMNs}}, {{paresthesias}}, subacute combined degeneration (abnormal myelination of dorsal and lateral columns). Lab Values: {{Elevated homocysteine, methylmalonic acid. Low methionine and succinyl-CoA. Shilling test for etiology}}. Pathophysiology: Required for homocysteine methyltransferase and methylmalonyl-CoA mutase. Caused by malabsoprtion (sprue, enteritis, Diphyllobothrium latum), pernicious anemia / gastric bypass surgery (lack of intrinsic factor), or termianl ileum absence (Crohn's disease). Treatment:
Vitamin B9 (folic acid) deficiency
Symptoms: {{Megaloblastic anemia, hypersegmented PMNs. NO NEUROLOGICAL SYMPTOMS (as opposed to B12)}}. Neural tube defects in embryos. Most common vitamin deficiency in the US. Lab Values: Pathophysiology: {{Required for methylation reactions (synthesis of DNA and RNA)}}. Due to phenytoin, sulfonamides, methotrexate, pregnancy, alcoholism. Lack of green leaves in diet. Treatment:
Vitamin B7 (biotin) deficiency
Symptoms: Epithelia...including GI tract!! Dermatitis, alopecia, enteritis. Caused by antibiotic use or {{excessive ingestion of raw egs.}} Lab Values: Pathophysiology: Required for carboxylatoin enzymes. Treatment:
Vitamin C (ascorbic acid) deficency
Symptoms: {{Scurvy - swollen gums, bruising/purpura, anemia, and poor wound healing}}. Perifollicular hyperkeratosis, loose teeth, hemorrhages. Lab Values: Elevated BT. Pathophysiology: {{Antioxidant;}} {{increases iron absorption}} {{necessary for hydroxylation of proline and lysine in collagen synthesis in the ENDOPLASMIC RETICULUM}}, and necessary for dopamine B-hydroxylase which converts dopamine to norepinephrine. Treatment:
Vitamin D deficiency
Symptoms: Rickets in children (bending bones), osteomalacia in adults (soft bones), hypocalcemic tetany. Lab Values: Pathophysiology: Caused by dietary deficiency or malabsorption (pancreatitis, cystic fibrosis, sprue, mineral oil intake). Needed for intestinal absorption of calcium and phosphate; increases resorption from bone. Cholecalcierfol formed by sun exposed skin, 25-D3 formed by liver, 1,25-D3 formed by kidney. Treatment:
Vitamin D excess
Symptoms: {{Hypercalcemia, hypercalcinuria, loss of appetite, stupor}}. Seen in sarcoidosis (increased activation of vitamin D by epilthelioid macrophages). Lab Values: Pathophysiology: Treatment:
Vitamin E deficiency
Symptoms: Acts as an antioxidant against free radicals...RBCS and eyes {{Hemolytic anemia (increased RBC fragility)}}, {{muscle weakness}}, subacute combined degeneration, {{retinitis pigmentosum (rods and cones are messed up)}}. Lab Values: Pathophysiology: Caused by dietary deficiency or malabsorption (p ancreatitis, cystic fibrosis, sprue, mineral oil intake). {{Functions as an antioxidant (protects against membrane free radical damage).}} Treatment:
Vitamien E excess
Symptoms: {{Cerebral hemorrhage, bleeding out}} (inhibits vitamin K and other clotting factors). Lab Values: Pathophysiology: Treatment:
Vitamin K deficiency
Symptoms: Neonatal hemorrhage because they have sterile guts thus are unable to synthesize vitamin K. Can also be caused by broad spectrum antibiotics or warfarin. Lab Values: Elevated PT and PTT, normal BT. Pathophysiology: Required for clotting factors II, VII, IX, X and protein C/S. Treatment:
Zinc deficiency
Symptoms: {{Delayed wound healing}}, {{hypogonadism}}, loss of adult hair (axillary, facial, pubic), {{dysgeusia}} (loss of sense of taste), anosmia. Predisposes to alcoholic cirrhosis. Lab Values: Pathophysiology: Required cofactor for 100+ enzymes; zinc finger (transcription factor motif). Treatment:
Effect of ethanol on blood sugar and liver metabolism
Symptoms: Hypoglycemia, hepatocellular steatosis, lactic acidosis. Lab Values: Pathophysiology: {{Increases NADH/NAD ratio in liver}}, causing diversion of pyruvate to lactate and OAA to malate thereby {{inhibiting glucoenogensis and stimulating fatty acid synthesis.}} Treatment:
Kwashiorkor
Symptoms: Skin lesions, edema, liver malfucntion (fatty change due to decrease apolioprotein synthesis). Small child with sowllen belly. Lab Values: Pathophysiology: Treatment:
Marasmus
Symptoms: Energy malnutrition resulting in tissue and muscle wasting, loss of subcutaneous fat and variable edema. Lab Values: Pathophysiology: Treatment:
Pyruvate dehydrogenase deficiency
Symptoms: {{Neurological defects, ketoacidosis.}} Lab Values: Pathophysiology: Can be congenitla or due to vitamin B1 deficiency (alcoholics). Treatment: Treat with increased intake of ketogenic nutrteins; ex. High fat content or high lysine/leucine.
Hereditary fructose intolerance
Symptoms: Hypoglycemia, jaundice, cirrhosis, vomiting. Lab Values: Pathophysiology: Autosomal recessive. {{Defect in aldolase B}}. {{Fructose-1-phosphate accumulates leading to decrease in available phosphate, which inhibits glycogenolysis and gluconeognesis.}} Treatment: Decrease intake of fructose and sucrose.
Essential fructosuria
Symptoms: Fructose in blood and urine; {{benign and asymptomatic.}} Lab Values: Pathophysiology: Autosomal recessive. Defect {{in fructokinase.}} Treatment:
Classical galactosemia
Symptoms: Failure to thrive, {{jaundice}}, hepatomegaly, {{infantile cataracts}}, mental retardation. Lab Values: Pathophysiology: Autosomal recessive. {{Defect in galactose-1-phosphate uridyltransferase}}. Damage caused by accumulation of galactitol which accumulates in the eye of the lens. Treatment: Exclude galactose and lactose from diet.
Galactokinase deficiency
Symptoms: Galactose in urine and blood, {{infantile cataracts}}. May present by {{failure to track objects or develop a social smile}}. {{Milder}} than classic galatosemia. Lab Values: Pathophysiology: Autosomal recessive. {{Defect in galactokinase. Leads to accmulation of galactitol}}. Treatment:
Lactase deficiency
Symptoms: Bloating, cramps, osmotic diarrhea after lactose ingestion. More common in African Americans and Asians. Lab Values: Pathophysiology: Deficiency in brush-border enzyme; unable to metabolize lactose to glucose/galactose thus it is never absorbed. Treatment: Avoid dairy products or add lactase pills.
Hyperammonemia without orotic aciduria
Symptoms: {{Tremor}}, {{slurring of speech}}, somnolence/drowsiness, vomiting, cerebral edema, {{blurring of vision}}. Lab Values: Low BUN, no orotic acid in blood and urine. Pathophysiology: Autosomal recessive. Defect in carbamoyl phosphate synthetase I. Excess NH4 depeletes alpha-ketoglutarate leading to inhibition of TCA cycle. Treatment: Limit protien in diet or benzoate/phenylbutryate to increase amino acid excretion.
Hyperammonemia with orotic aciduria
Symptoms: Tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision. Lab Values: Low BUN, orotic acid in blood and urine. Pathophysiology: X-linked recessive. Ornithine transcarbamoylase deficiency. Excess carbamoyl phosphate is converted to ortic acid. Treatment:
Phenylketonuria type 1
Symptoms: Mental retardation, growth retardation, {{seizures}}, {{fair skin}}, {{eczema, musty (mousy) body odor.}} Lab Values: Pathophysiology: Autosomal recessive. Defect in {{phenylalanine hydroxylase}}. Tyrosine becomes an essential amino acid. Treatment: Avoid phenylalanine until ~5-6. Pregnant PKU mothers must also avoid phenylalanine.
Phenylketonuria type 2
Symptoms: Mental retardation, growth retardation, seizures, fair skin, eczema, musty (mousy) body odor. {{Worse prognosis than PKU1}} since there is a decrease in dopamine synthesis. Lab Values: Pathophysiology: {{Defect in dihydrobiopterin reductase.}} Treatment:
Alkaptonuria
Symptoms: {{Dark connective tissue (ochronosis)}}, pigmented sclera, {{black urine}}, debilitating arthralgias. Lab Values: Pathophysiology: Autosomal recessive. {{Defect in homogentisic acid oxidase. Involved in tyrosine degradation pathway.}} Treatment:
Albinism
Symptoms: Increased risk of skin cancer due to decrease melanin (decreases UV DNA damage). Lab Values: Pathophysiology: Caused by lack of neural crest cell migration (melanocytes), defective tyrosinase (decreased melanin), defective tyrosine transporters (decrease tyrosine and thus melanin). Locus heterogenity. Treatment:
Homocystinuria
Symptoms: Mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (down and inward). Increased risk of vascular thrombosis and atherosclerosis. Lab Values: Elevated homocysteine in urine and blood. Cystine becomes an essential amino acid. Pathophysiology: Autosomal recessive. Due to defect in cystathionine synthase, decrease affinity for B6, or homocysteine methyltransferase deficiency. Treatment: Increase cysteine and decrease methionine in diet, also increase B9/B12. If due to low B6 affinity, give B6.
Cystinuria
Symptoms: Cystine staghorn calculi in urine. Lab Values: Pathophysiology: Autosomal recessive. Defect in dibasic amino acid transporter in proximal tubule. Unable to reabsorb cysteine, orthithine, lysine, arginine, and cystine. Treatment: Acetazolamide to alkalinize the urine.
Maple syrup urine disease
Symptoms: Severe CNS defects, mental retardation, and death. Lab Values: Urine smells like maple syrup. Pathophysiology: Defective branched chain amino acid dehydrogenase; increase ketoacids in blood (Ile, Leu, Val; especially leucine). Treatment:
Hartnup disease
Symptoms: Pellagra (dermatitis, diarrhea, dementia). Lab Values: Increase trytophan in urine and decrease absorption from gut. Pathophysiology: Autosomal recessive. Defective neutral amino acid transporter in instetinal and renal epithelial cells. Unable to synthesize niacin without its tryptophan precursor. Treatment:
Von Gierke's disease
Symptoms: Severe fasting hypoglycemia, hepatomegaly, increase glycogen in liver, lactic acidosis. Lab Values: Pathophysiology: Defective glucose-6-phosphatase. Treatment:
Pompe's disease
Symptoms: Cardiomegaly, muscle weakness, hepatomegaly. Lab Values: Pathophysiology: Defective lysosomal alpha-1,4-glucosidase Treatment:
Cori's disease
Symptoms: Similar to von Gierke's but milder; fasting hypoglycemia with normal lactic acid levels. Mild hepatomegaly Lab Values: Pathophysiology: Defective debrachning enzyme (alpha-1,6-glucosidase). Treatment:
McArdle's disease
Symptoms: Painful muscle cramps for ~20 minutes after activity; relieved once beta-oxidation kicks in. Lab Values: Myoglobinuria. No increase in lactic acid. Pathophysiology: Defective skeletal muscle glycogen phosphorylase. Cannot metabolize muscle glycogen. Treatment:
Fabry's disease
Symptoms: Burning peripheral neuropathy of hands/feet (acroparesthesia), angiokeratomas, cardiovascular/renal disease, hypohidrosis. Death due to renal failure. Lab Values: Increased ceramide trihexoside. Pathophysiology: X-linked recessive. Defect in alpha-galactosidase. Treatment:
Gaucher's disease
Symptoms: Hepatosplenomegaly, avascular necrosis of femur. Most common lysosomal storage disease. Lab Values: Increased glucocerebroside.Gaucher's cells (macrophages that look like crumpled tissue paper). Pathophysiology: Autosomal recessive. Defect in glucocerebroside. Treatment:
Niemann-Pick disease
Symptoms: Progressive neurodegeneration, hepatosplenomegaly, cherry red spots on macula. Lab Values: Increased sphingomyelin. Foam cells. Pathophysiology: Autosomal recessive. Defect in sphingomyelinase. Treatment:
Tay-Sachs disase
Symptoms: Progressive neurodegeneration, developmental delay, cherry-red spot on macula, NO HEPATOSPLENOMEGALY (vs. Neimann-Pick). Lab Values: Increased GM2 ganglioside. Lysosomes with onion skin. Pathophysiology: Autosomal recessive. Defect in hexosamidase A. Treatment:
Hurler's syndrome
Symptoms: Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly. Lab Values: Increased heparan sulftae, dermatan sulfate. Pathophysiology: Autosomal recessive. Defect in alpha-L-iduronidase. Treatment:
Hunter's syndrome
Symptoms: Mild Hurler's (developmental delay, airway obstruction due to macroglossia, gargoylism, hepatosplenomegaly), hearing loss, aggressive behavior, no corneal clouding or mental retardatoion. Lab Values: Increased heparan sulftae, dermatan sulfate. Pathophysiology: X-linked recessive. Defect in iduronate sulfatase. Treatment:
Hyperlipoproteinemia type I
Symptoms: Hyperchylomicronemia. Pancreatitis, hepatosplenomegaly, eruptive/pruritic xanthomas. No increased risk for atherosclerosis. Lab Values: Increased chylomicrons (TG, cholesterol). Pathophysiology: Lipoprotein lipase or apoliprpotein C-II deiciency. Treatment:
Hyperlipoproteinemia type II
Symptoms: Familial hypercholesterolemia. Accelerated atherosclerosis, tendon xanthomas (Achilles), and corneal arcus (ring around the cornea). Lab Values: Increased LDLs (cholesterol). Pathophysiology: Autosomal dominant. Absent or decreased LDL receptors. Treatment:
Hyperlipoproteinemia type III
Symptoms: Lab Values: High chylomicrons and IDL. Pathophysiology: ApoE2; unable to uptake chylomicrons in liver. Treatment:
Hyperlipoproteinemia type IV
Symptoms: Hypertriglyceridiemia. Pancreatitis. No increase in coronary artery disease. Lab Values: Increases VLDLs (TG). Normal cholesterol levels. Pathophysiology: Hepatic overproduction of VLDL. Treatment:
Abeta-lipoproteinemia
Symptoms: Failure to thrive, steatorrhea, acanthyocytosis (thorny RBC projections), ataxia, night blindness. Presents early in life. Lab Values: Intestinal biopsy shows accumulation of lipids and inability to export as chylomicrons. Pathophysiology: Autosomal recessive. Defect in apoB-100 and apoB-48 (microsomal transfer protein). Treatment:
Myoclonic epilepsy with ragged red fibers (MERRF)
Symptoms: Short stature, lactic acisos, hearing loss, exercise intolerance, poor night vision. Epilepsy triggered by startle. Lab Values: Ragged red fibers; clumbs of diseased mitochondria accumulate in muscle fibers. Pathophysiology: Displays heteroplasmy. Mother passes to all children; father to none. Treatment:
Leber's hereditary optic neuropathy
Symptoms: Loss of vision in one eye and then another. Lab Values: Pathophysiology: Displays heteroplasmy. Mother passes to all children; father to none. Degeneration of retinal ganglion cells. Treatment:
Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS)
Symptoms: Lab Values: Pathophysiology: Displays heteroplasmy. Mother passes to all children; father to none. Treatment:
Electron transport inhibitors
Symptoms: Rotenone, cyanide, antimycin A, or carbon monoxide toxicity. Lab Values: Pathophysiology: Directly inhibits electron transport, causing a decrease in protein gradient and block of ATP synthesis. Treatment:
ATPase inhibitors
Symptoms: Oligomycin toxicity. Lab Values: Pathophysiology: Directly inhibits mitochondrial ATPase, cuasing an increase in protein gradient. No ATP is produced because electron transport stops. Treatment:
Uncoupling agents
Symptoms: 2,4-DNP, aspirin, thermogenin in brown fat. Lab Values: Pathophysiology: Increase in membrane permability to hydrogen leading to a decrease in proton gradient and a increase in O2 consumption. ATP synthesis stops but ETC continues to produce heat. Treatment:
Carnitine palmitoyltransferase II deficiency (or carnitine deficency)
Symptoms: Hypoketotic hypoglycemia; weakness, hypotonia. Lab Values: Pathophysiology: Inability to transport long chain fatty acids into mitochondria resulting in toxic accumulation. Treatment:
Acyl-CoA dehydrogenase deficiency
Symptoms: Hypoketotic hypoglycemia, hyperammonemia. Lab Values: Elevated dicarboxylic acids. Pathophysiology: Unable to metabolism a given fatty acid (short, medium, long). Increased dicarboxylic acids, decrease glucose and ketones. Increased fatty acids in blood. Treatment:
Menkes disease
Symptoms: Hypopigmentation, lustlerless hair (matted, spare, pale), listlessness in young child that was healthy at birth. Lab Values: Low ceruloplasmin levels. Pathophysiology: X-linked recessive. Defect in copper transport; decreases activity of lysyl oxidase. Treatment:
Orotic aciduria
Symptoms: Megaloblastic anemia that can't be cured by B9/B12, failure to thrive. Lab Values: Elevated orotic acid, NORMAL ammonia/BUN levels. Pathophysiology: Defect in pyrimidine synthesis pathway (orotate phosphoribosyltransferase and orotidine 5'-phosphate decoarboxylase). Treatment: Oral uridine administration
Hypophosphatemic rickets
Symptoms: Soft bones, bowed legs, rachitic rosary (knobs at costochondral joints), Harrison's sulci, craniotabes (thinning of the skul), and growth retardation. Lab Values: Phosphate wasting at the proximal tubule. Pathophysiology: Vitamin D resistant rickets. X-linked dominant. Treatment: