TABLE of GENETIC DISORDERS

Disease Cystic Fibrosis

Category

Pathogenesis / Heredity Autosomal Recessive. CFTR gene defect on Chrom 7 ------> No Cl- transport and failure to hydrate mucous secretions (no NaCl transport) ------> excessively viscous mucoid exocrine secretions Autosomal Recessivecongenital pancytopenia.

Pathology, Cardinal Symptoms Meconium ileus (caused by thick, mucoid meconium), respiratory bronchiectasis,Pseudomonas pne umonia, pancreatic insufficiency, hypertonic (high Cl-concentration) sweat. Normocytic anemia with neutropenia. Short stature, microcephaly, hypogenitalism, strabismus, anomalies of the thumbs, radii, and kidneys, mental retardation, and microphthalmia.

Fanconi Anemia

Hartnup's Disease

Autosomal Recessive. Defect in GI uptake of neutral amino acids ------> malabsorption oftryptophan (niacin precursor) ------> niacin deficiency among other things. Autosomal Recessive. Defect in dynein arms ------> lost motility of cilia

Pellagra-like syndrome (diarrhea, dementia, dermatitis), lightsensitive skin rash, temporary cerebellar ataxia.

Kartagener's Syndrome

Recurrent sinopulmonary infections (due to impaired ciliary tract). Situs inversus, due to impaired ciliary motion during embryogenesis: lateral transposition of lungs, abdominal and thoracic viscera are on opposite sides of the body as normal. Possible dextrocardia, male sterility. Neurologic defects. Treatment: Increase intake of ketogenic nutrients (leucine, lysine) ------> increase formation of Acetyl-CoA from other sources. Dry skin, melanomas, pre-

Pyruvate Dehydrogenase Deficiency

Autosomal Recessive.Pyruvate Dehydrogenasedeficiency -----> buildup of lactate and pyruvate ------>lactic acidosis.

Xeroderma

Autosomal Recessive. Defect in

Pigmentosum

DNA repair, inability to repair thymine dimers resulting from UVlight exposure ------> excessive skin damage and skin cancer. Autosomal Dominant Disorders Autosomal Dominant Disorders A group of inherited diseases associated with hypercholestrolemia. Autosomal Dominant.

malignant lesions, other cancers. Ophthalmic and neurologic abnormalities.

Familial Hypercholestero lemia Hereditary Hemorrhagic Telangiectasia (Osler-WeberRendu Syndrome) Hereditary Spherocytosis

Heterozygous: accelerated atherosclerosis. Homozygous: accelerated atherosclerosis, MI by age 35, xanthomas. Telangiectasias of skin and mucous membranes.

Autosomal Dominant Disorders

Autosomal Dominant. Band3 deficiency in RBC membrane -----> spherical shape to cells. Other RBC structural enzyme deficiencies can cause it, too. Autosomal Dominant, 100% penetrance. Genetic defect on Chrom 4 -----> atrophy of caudate nuclei, putamen, frontal cortex.

Sequestration of spherocytes in spleen ------> hemolytic anemia.

Huntington's Disease

Autosomal Dominant Disorders

Progressive dementia with onset in adulthood, choreiform movements, athetosis.

Marfan's Syndrome

Autosomal Dominant Disorders

Autosomal Dominant.Fibrillin deficiency -----> faulty scaffolding in connective tissue (elastin has no anchor). Autosomal Dominant. NF1 gene defect (no GTPase protein) ------> dysregulation of Ras tumor-suppressor protein.

Arachnodactyly, dissecting aortic aneurysms, ectopia lentis (subluxation of lens), mitral valve prolapse. Multiple neurofibromas (Caf?au Lait spots) which may become malignant,Lisch nodules (pigmented hamartomas of the iris). Increased risk for tumors: pheochromocytoma, Wilms tumor, Rhabdomyosarcoma, leukemias.

Neurofibromatos is (Von Recklinghausen Disease)

Autosomal Dominant Disorders

Tuberous Sclerosis

Autosomal Dominant Disorders

Autosomal Dominant.

Tubers (glial nodules), seizures, mental retardation. Associated with adenoma sebaceum (facial lesion), myocardial rhabdomyomas, renal angiomyolipomas.

Von HippelLindau Syndrome

Autosomal Dominant Disorders

Autosomal Dominant, short arm of chromosome 3. Same genetic region is associated with incidence ofrenal cell carcinoma. Autosomal Recessive.Aldolase B deficiency ------> buildup of Fructose-1-Phosphate in tissues ------> inhibit glycogenolysis and gluconeogenesis. Autosomal Recessive. Inability to convert galactose to glucose ------> accumulation of galactose in many tissues. (1) Classic form: Galactose-1phosphate Uridyltransferasedeficiency. (2) Rarer form:Galactokinase deficiency.

(1) Hemangioblastomas of cerebellum, medulla, or retina, (2) adenomas, (3) cysts in visceral organs. High risk for renal cell carcinoma. Severe hypoglycemia. Treatment: Remove fructose from diet.

Congenital Fructose Intolerance

Carbohydr ate Metabolis m Defect

Galactosemia

Carbohydr ate Metabolis m Defect

Failure to thrive, infantile cataracts, mental retardation. Progressive hepatic failure, cirrhosis, death. Galactokinase-deficiency: infantile cataracts are prominent. Treatment: in either case,remove galactose from diet. Mental retardation, ataxic gait, seizures.Inappropriate laughter. "Cry of the cat." Severe mental retardation, microcephaly, catlike cry. Low birth-weight, roundface, hypertelorism (wide-set eyes), low-set ears, epicanthal folds. Most common cause of mental retardation. Will see epicanthal folds, simian crease, brushfield spots in eyes. Associated syndromes: congenital heart disease, leukemia,premature Alzheimer's disease (same morphological changes). Mental retardation, micrognathia, rocker-bottom feet, congenital heart disease, flexion deformities of fingers. Death by 1 year old. Mental retardation, microphthalmia, cleft lip and palate, polydactyly, rocker-

Angelman Syndrome

Chromoso mal

Deletion of part of short arm of chromosome 15, maternal copy. An example of genomic imprinting. 5p-, deletion of the long arm of chromosome 5.

Cri du Chat Syndrome

Chromoso mal

Down Syndrome (Trisomy 21)

Chromoso mal

Trisomy 21, with risk increasing with maternal age. Familial form (no ageassociated risk) is translocation t(21,x) in a minority of cases.

Edward's Syndrome (Trisomy 18) Patau's Syndrome

Chromoso mal

Trisomy 18

Chromoso mal

Trisomy 13

(Trisomy 13)

bottom feet, congenital heart disease. Similar to and more severe than Edward's Syndrome. Death by 1 year old. Chromoso mal Deletion of part of short arm of chromosome 15, paternal copy. An example of genomic imprinting. Progressively longertandem repeats on the long arm of the X-chromosome. The longer the number of repeats, the worse the syndrome. Tandem repeats tend to accumulate through generations. Non-disjunction of the sex chromosome during Anaphase I of meiosis ------> Trisomy (47,XXY) Mental retardation, short stature, hypotonia, obesity and huge appetite after infancy. Small hands and feet, hypogonadism. Second most common cause of mental retardation next to Down Syndrome. Macroorchidism (enlarged testes) in males.

Prader-Willi Syndrome

Fragile-X Syndrome

Chromoso mal Sex chromoso me

Klinefelter's Syndrome (XXY)

Chromoso mal Sex chromoso me

Hypogonadism, tall stature, gynecomastia. Mild mental retardation. Usually not diagnosed until after puberty. One Barr body seen on buccal smear. Streak gonads, primary amenorrhea, webbed neck, short stature, coarctation of Aorta, infantile genitalia.No mental retardation. No Barr bodies visible on buccal smear. Usually phenotypically normal. May see menstrual abnormalities or mild mental retardation in some cases.

Turner's Syndrome (XO)

Chromoso mal Sex chromoso me

Non-disjunction of the sex chromosome during Anaphase I of meiosis ------> Monosomy (45,X)

XXX Syndrome

Chromoso mal Sex chromoso me

Trisomy (47,XXX) and other multiple X-chromosome abnormalities.

Ehlers-Danlos Syndrome

Connectiv e Tissue disease

Various defects in collagen synthesis.

Laxity of joints, hyperextensibility of skin, poor wound healing, aneurysms.

Type-I: Autosomal dominant, mildest form. Type-IV: autosomal dominant. Defect in reticular collagen (typeIII) Type-VI: autosomalrecessive. Type-VII: Defect in collagen type I Type-IX: X-linked recessive

Type-I: Diaphragmatic hernia. Common, normal life-expectancy. Type-IV: Ecchymoses, arterial rupture. Dangerousdue to rupture aneurysms. Type-VI: Retinal detachment, corneal rupture

Osteogenesis Imperfecta

Connectiv e tissue disease

Defects in Collagen Type Iformation.

Multiple fractures after birth, blue sclerae, thin skin, progressive deafness in some types (due to abnormal middle ear ossicles). Type-I is most common;TypeII is most severe;Type-IV is mildest form.

Cori's Disease (Glycogen Storage Disease Type III)

Glycogen Storage Disease

Autosomal Recessive.Debranching enzymedeficiency (can only break down linear chains of glycogen, not at branch points) ------> accumulate glycogen in liver, heart, skeletal muscle. Autosomal Recessive.muscle phosphorylasedeficiency (cannot utilize glycogen in skeletal muscle) ------> accumulation of glycogen in skeletal muscle. Autosomal Recessive.alpha1,4-Glucosidasedeficiency (cannot break down glycogen) -----> accumulate glycogen in liver, heart, skeletal muscle. Autosomal Recessive.Glucose6-Phosphatasedeficiency (cannot break down glycogen) -----> accumulate glycogen in liver and kidney.

Stunted growth, hepatomegaly, hypoglycemia.

McArdle's Disease (Glycogen Storage Disease Type V) Pompe's Disease (Glycogen Storage Disease Type II) Von Gierke's Disease (Glycogen Storage Disease Type I) Hemophilia A (Factor VIII Deficiency) Hemophilia B (Factor IX Deficiency) Von Willebrand Disease

Glycogen Storage Disease

Muscle cramps, muscle weakness, easy fatigability. Myoglobinuria with strenuous exercise.

Glycogen Storage Disease

Cardiomegaly, hepatomegaly, and systemic findings, leading to early death.

Glycogen Storage Disease

Severe fastinghypoglycemia, hepatomegaly from lots of glycogen in liver.

Hemophili a Hemophili a Hemophili a

X-Linked Recessive. Factor VIII deficiency X-Linked Recessive. Factor IX deficiency. Autosomal dominant and recessive varieties. Von Willebrand Factordeficiency -----> defect in initial formation of platelet plugs, and shorter half-life of Factor VIII in blood.

Hemorrhage, hematuria, hemarthroses. Prolonged PTT. Milder than Hemophilia A. Hemorrhage, hematuria, hemarthroses. Prolonged PTT. Hemorrhage, similar to hemophilia. Type-I: Most mild. Type-II: Intermediate. Type-III: most severe, with recessive inheritance (complete absence). Cerebellar ataxia, telangiectasia

Ataxia-

Immune

Autosomal Recessive. Unknown.

Telangiectasia

deficiency Combined Deficiency

Numerous chromosomal breaks and elevated AFP is found. Symptomatic by age 2 years.

(enlarged capillaries of face and skin),B and T-Cell deficiencies, IgA deficiency.

Ch?iak-Higashi Syndrome

Immune deficiency Phagocyte Deficiency

Defect in polymerization of microtubules in neutrophils -----> failure in neutrophilmigration and phagocytosis. Also results in failure in lysosomal function in neutrophils. X-Linked (usually) NADPH Oxidase deficiency ------> no formation of peroxides and superoxides ------> no oxidative burst in phagocytes. T-Cell deficiency specific toCandida.

Recurrent pyogenic infections, Staphylococcus, Streptococcus.

Chronic Granulomatous Disease

Immune deficiency Phagocyte Deficiency

Failure of phagocytes leads to susceptibility to infections, especially Staph Aureus and Aspergillus spp. B and T cells usually remain normal. Selective recurrent Candidainfections. Treat with anti-fungal drugs.

Chronic Mucocutaneous Candidiasis

Immune deficiency T-Cell Deficiency

Job's Syndrome

Immune deficiency Phagocyte Deficiency

A failure to producegammaInterferon by T-Helper cells, leading to an increase in TH2 cells (no negative feedback) -----> excessively high levels ofIgE. IgA deficiency may be due to a failure of heavy-chain gene switching.

High histamine levels, eosinophilia. Recurrent cold(noninflammatory) Staphylococcal abscesses(resulti ng from high histamine), eczema. The most common congenital immune deficiency. There also exists selective IgM and IgG deficiencies, but they are less common. Severe deficiency in both humoral and cellular immunity, due to impaired DNA synthesis. Bone marrow transplant may be helpful in treatment.

Selective IgA Deficiency

Immune deficiency B-Cell Deficiency

Severe Combined Immunodeficien cy (SCID)

Immune deficiency Combined Deficiency

Autosomal Recessive.Adenosine Deaminasedeficiency ------> accumulation of dATP ------> inhibit ribonucleotide reductase ------> decrease in DNA precursors Failure of development of the 3rd and 4thPharyngeal Pouches ------> agenesis of the thymus and parathyroid glands. Inability to mount initial IgMresponse to the capsular polysaccharides of

Thymic Aplasia (DiGeorge Syndrome)

Immune deficiency T-Cell Deficiency

T-Cell deficiency from no thymus. Hypocalcemic tetany from primary parathyroid deficiency.

Wiskott-Aldrich Syndrome

Immune deficiency

In infancy, recurrent pyogenic infections, eczema, thrombocytopenia, excessive

pyogenic bacteria. Combined Deficiency X-Linked Agammaglobulin emia (Bruton's Disease) Immune deficiency B-Cell Deficiency Lysosomal Storage Disease X-Linked. Mutation in gene coding for tyrosine kinasecauses failure of Pre-B cells to differentiate into BCells. X-Linked Recessive. alphaGalactosidase A deficiency -----> buildup of ceramide trihexoside in body tissues. Autosomal Recessive.Glucocerebrosidase deficiency ------> accumulation of glucocerebrosides (gangliosides, sphingolipids) in lysosomes throughout the body.

bleeding. IgG levels remain normal.

Recurrent pyogenic infections after 6 months (when maternal antibodies wear off). Can treat with polyspecific gamma globulin preparations. Angiokeratomas (skin lesions) over lower trunk, fever, severe burning pain in extremities, cardiovascular and cerebrovascular involvement.

Fabry's Disease

Gaucher's Disease

Lysosomal Storage Disease

Type-I: Adult form. 80% of cases, retain partial activity. Hepatosplenomegaly, erosion of femoral head, mild anemia. Normal lifespan with treatment. Type-II: Infantile form. Severe CNS involvement. Death before age 1. Type-III: Juvenile form. Onset in early childhood, involving both CNS and viscera, but less severe than Type II.

Niemann-Pick Lipidosis

Lysosomal Storage Disease

Autosomal Recessive.Sphingomyelinased eficiency ------> accumulation of sphingomyelin in phagocytes.

Sphingomyelin-containingfoamy histiocytes in reticuloendothelial system and spleen. Hepatosplenomegaly,anemia, fever, sometimes CNS deterioration. Death by age 3. Similar to but less severe than Hurler Syndrome. Hepatosplenomegaly, micrognathia, retinal degeneration, joint stiffness, mild retardation, cardiac lesions. Gargoyle-like facies, progressive mental deterioration, stubby fingers, death by age 10. Similar to Hunter's Syndrome.

Hunter's Syndrome

Lysosomal Storage Disease

X-Linked Recessive. Liduronosulfate sulfatasedeficiency ------> buildup ofmucopolysaccharides(hepar an sulfate and dermatan sulfate) Autosomal Recessive.alpha-Liduronidasedeficiency ------> accumulation ofmucopolysaccharides(hepar an sulfate, dermatan sulfate) in heart, brain, liver, other organs. Autosomal

Hurler's Syndrome

Lysosomal Storage Disease

Tay-Sachs

Lysosomal

CNS degeneration,

Disease

Storage Disease

Recessive.Hexosaminidase Adeficiency ------> accumulation of GM2ganglioside in neurons. Autosomal Recessive.Tyrosinase deficienc y ------> inability to synthesize melanin from tyrosine. Can result from a lack of migration of neural crest cells. Autosomal Recessive.Homogentisic Oxidasedeficiency (inability to metabolize Phe and Tyr) ------> buildup and urinary excretion of homogentisic acid. Autosomal Recessive.Cystathionine synthasedefect (either deficiency, or lost affinity for pyridoxine, Vit. B6) ------> buildup of homocystine and deficiency of cysteine.

retardation, cherry red-spot of macula, blindness (amaurosis). Death before age 4. Depigmentation, pink eyes, increased risk of skin cancer.

Albinism

Nitrogen Metabolis m Defect

Alkaptonuria

Nitrogen Metabolis m Defect

Urine turns dark and black on standing, ochronosis(dark pigmentation of fibrous and cartilage tissues), ochronotic arthritis, cardiac valve involvement. Disease is generally benign. Mental retardation, ectopia lentis, sparse blond hair, genu valgum, failure to thrive, thromboembolic episodes, fatty changes of liver. Treatment: Cysteine supplementation, give excess pyridoxine to compensate for lost pyridoxine affinity. Hyperuricemia (gout), mental retardation, self-mutilation (autistic behavior), choreoathetosis, spasticity.

Homocystinuria

Nitrogen Metabolis m Defect

Lesch-Nyhan Syndrome

Nitrogen Metabolis m Defect

X-Linked Recessive.HypoxanthineGuanine Phosphoribosyltransferase (HGPRT) deficiency ------> no salvage pathway for purine resynthesis ------> buildup of purine metabolites Autosomal Recessive. Deficiency of branched chain keto-acid decarboxylase ------> no degradation of branched-chain amino acids ------> buildup of isoleucine, valine, leucine. Autosomal Recessive.Phenylalanine hydroxylase deficiency (cannot break down Phe nor make Tyr) ------> buildup of phenylalanine, phenyl ketones (phenylacetate, phenyl lactate, phenylpyruvate) in body tissues and CNS.

Maple Syrup Urine Disease

Nitrogen Metabolis m Defect

Severe CNS defects, mental retardation, death. Person smells like maple syrup or burnt sugar. Treatment:remove the amino acids from diet. Symptoms result from accumulation of phenylalanine itself. Mental deterioration, hypopigmentation (blond hair and blue eyes), mousy body odor (from phenylacetic acid in urine and sweat). Treatment: remove phenylalanine from diet.

Phenylketonuria (PKU)

Nitrogen Metabolis m Defect

Glucose-6Phosphate Dehydrogenase (G6PD) Deficiency

RBC Disease

X-Linked Recessive.Glucose-6Phosphate Dehydrogenase (G6PD)deficiency ------> no hexose monophosphate shunt -----> deficiency in NADPH -----> inability to maintainglutathione in reduced form, in RBC's Autosomal Recessive. Defect in hexokinase, glucose-phosphate isomerase, aldolase, triosephosphate isomerase, phosphate-glycerate kinase, or enolase. Any enzyme in glycolysis pathway. Autosomal Recessive.

Susceptibility to oxidative damage to RBC's, leading to hemolytic anemia. Can be elicited by drugs (primaquine, sulfonamides, aspirin), fava beans (favism). More prevalent in blacks. Hemolytic anemia results from any defect in the glycolysis pathway, as RBC's depend on glycolysis for energy.

Glycolytic enzyme deficiencies

RBC Disease

Autosomal Recessive Polycystic Kidney Disease (ARPKD) Bartter's Syndrome Fanconi's Syndrome Type I (Child-onset cystinosis) Fanconi's Syndrome II (Adult-onset) Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Renal

Numerous, diffuse bilateral cysts formed in the collecting ducts. Associated with hepatic fibrosis.

Renal

Juxtaglomerular Cell Hyperplasia, leading toprimary hyper-reninemia. Autosomal Recessive. Deficient resorption in proximal tubules.

Elevated renin and aldosterone, hypokalemic alkalosis. No hypertension. (1) Cystine deposition throughout body, cystinuria. (2) Defective tubular resorption leads to amino-aciduria, polyuria, glycosuria, chronic acidosis;Hypophosphatemia an dVitamin-D-resistant Rickets. Similar to Fanconi Syndrome Type I, but without the cystinosis. Adult onsetosteomalacia, aminoaciduria, polyuria, glycosuria. Numerous, disparate, heterogenous renal cysts occurring bilaterally. Onset in adult life. Associated with liver cysts.

Renal

Renal

Autosomal Recessive. Defective resorption in proximal tubules.

Renal Autosomal Dominant Disorders

Autosomal Dominant.

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Front Back Chr: 15 Mx: Inactivation/deletion/uniparental disomy. Imprinting. Deletion of active paternal allele. Hx: Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia. Chr: 15 Mx: Inactivation/deletion/uniparental disomy. Imprinting. Deletion of active maternal allele. Hx: Mental retardation, seizures, ataxia, inappropriate laughter ("happy puppet"). Gn: FGFR3 Mx: AD Fx: Cell-signaling defect Hx: Dwarfism, short limbs, head+trunk same size. Assoc: Adv. paternal age. Chr: 16 Gn: APKD1 (point mutation) Fx: Always bilateral massive kidney enlargement of kidneys due to multiple large cysts. Onset: Adult Hx: Flank pain, hematuria, HTN, progressive renal failure. Assoc: Polycystic liver dz, berry aneurysms, mitral valve prolapse. Chr: 5 Gn: APC (deletion) Mx: AD Fx: Colon covered with adenomatous polyps after puberty, always progresses to colon CA unless resected. Gn: LDLR Mx: AD Fx: Hetero - 300 mg/dL, homo - 700+. Hx: Severe atherosclerotic dz early in life, tendon xanthomas (Achilles), MI < 20 y/o. Mx: AD Fx: Inherited disorder of blood vessels Hx: Telangiectasia, epistaxis, skin discolorations, AVMs.

Prader-Willi Syndrome

Angelman Syndrome

Achondroplasia

Autosomal-Dominant Polycystic Kidney Disease

Familial Adenomatous Polyposis

Familial Hypercholesterolemia (HLE IIA)

Hereditary Hemorrhagic Telangiectasia (OslerWeber-Rendu)

Hereditary Spherocytosis

Mx: AD Gn: Spectrin/Ankyrin defect Fx: Spheroid erythrocytes Hx: Hemolytic anemia, MCHC Tx: Splenectomy Chr: 4 Mx: AD, CAC-repeat Hx: Depression, progressive dementia, choreiform movements, caudate atrophy, GABA+ACh. S/S 20-50 y/o. Gen: Fibrillin Mx: AD Hx: Tall w/long extremities, pectus excavatum, hyperextensive joints, arachnodactyly, aortic cystic medial necrosisaortic dissection, floppy mitral valve, lens subluxation. Mx: AD Hx: Pancreas+Parathyroid+Pituitary Mx: AD Gen: Ret Hx: Thyroid+Medulla Chr: 17q Mx: AD Gen: NF1 Hx: Cafe-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas). Assoc: Skeletal disorders (e.g., scoliosis), optic gliomas, pheochromocytomas, tumors. Chr Mx: AD Gen: NF2 Hx: Bilateral acoustic neuroma, juvenile cataracts. Mx: AD (incomplete penetrance, variable presentation) Hx: Facial lesions (adenoma sebaceum), hypopigmented "ash leaf spots" on skin, cortical+retinal hamartomas, seizures, mental retardation, renal cysts+angiomyolipomas, cardiac rhabdomyomas, astrocytomas. Chr: 3p Mx: AD, deletion. Gen: VHL (tumor suppressor) Fx: Constituitive HIF (transcription factor) expression,

Huntington's Disease

Marfan's Syndrome

Multiple Endocrine Neoplasia 1

Multiple Endocrine Neoplasia 2

Neurofibromatosis 1 (von Recklinghausen's Disease)

Neurofibromatosis 2

Tuberous sclerosis

von Hippel-Lindau Disease

angiogenic growth factor activation. Hx: Hemangioblastomas (retina/cerebellum/medulla), bilateral renal cell carcinoma, other tumors. Mx: AR Gn: Orotic acid phosphoribosyltransferase or orotidine 5'-phosphate decarboxylase Fx: Orotic acidUMP Hx: orotic acid in urine, megaloblastic anemia (B12/folate no help), failure to thrive, no NH4. Tx: PO uridine Gn: Adenosine deaminase Fx: Purine salvage deficiency, no lymphocytes. Hx: SCID. Mx: XR Gn: HGPRT Fx: Purine salvage deficiency, HypoxanthineIMP/GuanineGMP, uric acid Hx: Retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis. Fx: Lysosomal storage disorder, can't add mannose-6phosphate to proteins, lysosomal proteins exported outside cell, inclusions. Hx: Coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes. Fatal in childhood. Fx: Microtubule polymerization defect, phagocytosis. Hx: Recurrent pyogenic infections, partial albinism, peripheral neuropathy. Gn: Dynein Fx: Immotile cilia, dynein arm defect. Hx: Male/female infertility, bronchiectasis, sinusitis. Assoc: Situs inversus. Gn: COL3 Fx: Faulty collagen synth. Hx: Hyperextensible skin, easy bruising/bleeding, hypermobile joints. Assoc: Joint disloc, berry aneurysms, organ rupture. Mx: AD (common) Gn: COL1 Hx: Multiple fractures w/minimal trauma, blue sclerae, hearing loss (abnormal middle-ear bones), dental imperfections.

Orotic Aciduria

Adenosine Deaminase Deficiency

Lesch-Nyhan Syndrome

I-Cell Disease

Chediak-Higashi Syndrome

Kartagener's Syndrome

Ehlers-Danlos Syndrome

Osteogenesis Imperfecta

Alport's Syndrome

Mx: XR Gn: COL4 Hx: Progressive hereditary nephritis, deafness, ocular disturbances. Chr: 7 Mx: AR Gn: CFTR (d508F)abnormal foldingdegradation before surface Fx: CFTR is active chloride pump, secretes in lungs, reabsorbs from sweat. Secreton of abnormally thick mucus (lungs, pancreas, liver). Hx: Recurrent pulm infections (Pseudomonas, S. aureus), chronic bronchitis, bronchiectasis, pancreatic insuf. (malabsorption, steatorrhea), meconium ileus, male infertility (vas deferens absent), ADEK-deficiency. Assoc: Sweat test Tx: N-acetylcysteine to loosen plugs. Mx: XR Gn: DMD (frameshift), high rate of spontaneous mutation. Fx: Accelerated muscle breakdown (dystrophin anchors fibers). Hx: Progressive weakness, start in pelvic girdle, goes up. Pseudohypertrophy of calf muscles (fibrofatty replacement), cardiac myopathy. Onset < 5 y/o. Need arms to stand (Gowers' maneuver). Dx: CPK, biopsy. Mx: XR Gn: DMD Hx: Less severe than Duchenne's. Onset in adol/early adult. Hx: Progressive weakness, start in pelvic girdle, goes up. Pseudohypertrophy of calf muscles (fibrofatty replacement), cardiac myopathy. Need arms to stand (Gowers' maneuver). Dx: CPK, biopsy. Mx: XR Gn: FMR1 (CGG repeat) Hx: Retardation (2nd after Down), macro-orchidism, long face w/large jaw, large everted ears, autism, mitral valve prolapse. Assoc: Chromosomal breakage Mx: Trisomy 21 Hx: Retardation, flat facies, epicanthal folds, simian crease, 1st 2 toes gap, duodenal atresia, septum primum ASD. Assoc: ALL, Alzheimer's.

Cystic Fibrosis

Duchenne's Muscular Dystrophy

Becker's Muscular Dystrophy

Fragile X Syndrome

Down's Syndrome

Dx: Pregnancy quad screen - AFP, estriol, b-hCG, inhibin A. Nuchal translucency in usound. Mx: Trisomy 18 Hx: Severe retardation, micrognathia, clenched hands, heart dz. Mx: Trisomy 13 Hx: Cleft lip/palate, holoprosencephaly, polydactyly, heart dz. Mx: 5pHx: Microcephaly, retardation, high-pitched cry, epicanthal folds, cardiac problems. Mx: 7q- (esp. elastin) Hx: Elfin facies, retardation, [Ca] (vitD sens), good talker, very friendly, cardiovascular problems. Mx: 22q11Fx: CATCH-22: Cleft palate, Abnormal facies, Thymic aplasia, Cardiac defects, Hypocalcemia (parathyroid aplasia). Aberrant development of 3rd/4th branchial pouches. Hx: Thymic, parathyroid, cardiac defects. Mx: 22q11Fx: CATCH-22: Cleft palate, Abnormal facies, Thymic aplasia, Cardiac defects, Hypocalcemia (parathyroid aplasia). Aberrant development of 3rd/4th branchial pouches. Hx: Palate, facial, cardiac defects. Mx: XR Fx: NADPHGlutathioneHemolysis. Hx: Blacks, malarial resistance Assoc: Heinz bodies (oxidized hemoglobin), Bite cells (phagocytic removal of Heinz bodies)

Edwards' Syndrome

Patau's Syndrome

Cri-du-chat Syndrome

Williams Syndrome

DiGeorge Syndrome

Velocardiofacial Syndrome

G6PD Deficiency

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