Disease Category Pathogenesis / Heredity Pathology, Cardinal Symptoms
Cystic Fibrosis 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 Meconium ileus (caused by thick, mucoid meconium), respiratory bronchiectasis,Pseudomonas pneumonia, pancreatic insufficiency, hypertonic (high Cl-concentration) sweat.
Fanconi Anemia Autosomal Recessive congenital pancytopenia. Normocytic anemia with neutropenia.Short stature, microcephaly, hypogenitalism, strabismus, anomalies of the thumbs, radii, and kidneys, mental retardation, and microphthalmia.
Hartnup’s Disease Autosomal Recessive. Defect in GI uptake of neutral amino acids ——> malabsorption oftryptophan (niacin precursor) ——> niacin deficiency among other things. Pellagra-like syndrome (diarrhea, dementia, dermatitis), light-sensitive skin rash, temporary cerebellar ataxia.
Kartagener’s Syndrome Autosomal Recessive. Defect in dynein arms ——> lost motility of cilia 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.
Pyruvate Dehydrogenase Deficiency Autosomal Recessive. Pyruvate Dehydrogenase deficiency ——> buildup of lactate and pyruvate ——> lactic acidosis. Neurologic defects.Treatment: Increase intake of ketogenic nutrients (leucine, lysine) ——> increase formation of Acetyl-CoA from other sources.
Xeroderma Pigmentosum Autosomal Recessive. Defect in DNA repair, inability to repair thymine dimers resulting fromUV-light exposure ——> excessive skin damage and skin cancer. Dry skin, melanomas, pre-malignant lesions, other cancers. Ophthalmic and neurologic abnormalities.
Familial Hypercholesterolemia Autosomal Dominant Disorders Autosomal Dominant. LDL-Receptor defect. Heterozygous: accelerated atherosclerosis. Homozygous: accelerated atherosclerosis, MI by age 35, xanthomas.
Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome) Autosomal Dominant Disorders Autosomal Dominant. Telangiectasias of skin and mucous membranes.
Hereditary Spherocytosis Autosomal Dominant Disorders Autosomal Dominant. Band-3 deficiency in RBC membrane ——> spherical shape to cells. Other RBC structural enzyme deficiencies can cause it, too. Sequestration of spherocytes in spleen ——> hemolytic anemia.
Huntington’s Disease Autosomal Dominant Disorders Autosomal Dominant, 100% penetrance.Genetic defect on Chrom 4 ——> atrophy of caudate nuclei, putamen, frontal cortex. 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). Arachnodactyly, dissecting aortic aneurysms, ectopia lentis (subluxation of lens), mitral valve prolapse.
Neurofibromatosis (Von Recklinghausen Disease) Autosomal Dominant Disorders Autosomal Dominant. NF1 gene defect (no GTPase protein) ——> dysregulation of Ras tumor-suppressor protein. Multiple neurofibromas (Café au Lait spots) which may become malignant,Lisch nodules (pigmented hamartomas of the iris).Increased risk for tumors: pheochromocytoma, Wilms tumor, Rhabdomyosarcoma, leukemias.
Tuberous Sclerosis Autosomal Dominant Disorders Autosomal Dominant. Tubers (glial nodules), seizures, mental retardation. Associated with adenoma sebaceum (facial lesion), myocardial rhabdomyomas, renal angiomyolipomas.
Von Hippel-Lindau Syndrome Autosomal Dominant Disorders Autosomal Dominant, short arm of chromosome 3. Same genetic region is associated with incidence of renal cell carcinoma. (1) Hemangioblastomas of cerebellum, medulla, or retina, (2) adenomas, (3) cysts in visceral organs. High risk for renal cell carcinoma.
Congenital Fructose Intolerance Carbohydrate Metabolism Defect Autosomal Recessive. Aldolase B deficiency ——> buildup of Fructose-1-Phosphate in tissues ——> inhibit glycogenolysis and gluconeogenesis. Severe hypoglycemia. Treatment: Remove fructose from diet.
Galactosemia Carbohydrate Metabolism Defect Autosomal Recessive. Inability to convert galactose to glucose ——> accumulation of galactose in many tissues.(1) Classic form: Galactose-1-phosphate Uridyltransferase deficiency.(2) Rarer form: Galactokinase deficiency. 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.
Angelman Syndrome Chromosomal Deletion of part of short arm of chromosome 15, maternal copy. An example of genomic imprinting. Mental retardation, ataxic gait, seizures.Inappropriate laughter.
Cri du Chat Syndrome Chromosomal 5p-, deletion of the long arm of chromosome 5. “Cry of the cat.” Severe mental retardation, microcephaly, cat-like cry. Low birth-weight, round-face, hypertelorism (wide-set eyes), low-set ears, epicanthal folds.
Down Syndrome(Trisomy 21) Chromosomal Trisomy 21, with risk increasing with maternal age. Familial form (no age-associated risk) is translocation t(21,x) in a minority of cases. Most common cause of mental retardation. Will see epicanthal folds, simian creasebrushfield spots in eyes. Associated syndromes: congenital heart diseaseleukemia,premature Alzheimer’s disease (same morphological changes).
Edward’s Syndrome(Trisomy 18) Chromosomal Trisomy 18 Mental retardation, micrognathia, rocker-bottom feet, congenital heart disease, flexion deformities of fingers. Death by 1 year old.
Patau’s Syndrome(Trisomy 13) Chromosomal Trisomy 13 Mental retardation, microphthalmia, cleft lip and palate, polydactyly, rocker-bottom feet, congenital heart disease. Similar to and more severe than Edward’s Syndrome. Death by 1 year old.
Prader-Willi Syndrome Chromosomal Deletion of part of short arm of chromosome 15, paternal copy. An example of genomic imprinting. Mental retardation, short stature, hypotonia, obesity and huge appetite after infancy. Small hands and feet, hypogonadism.
Fragile-X Syndrome ChromosomalSex chromosome Progressively longer tandem 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. Second most common cause of mental retardation next to Down Syndrome. Macro-orchidism (enlarged testes) in males.
Klinefelter’s Syndrome (XXY) ChromosomalSex chromosome Non-disjunction of the sex chromosome during Anaphase I of meiosis ——> Trisomy (47,XXY) Hypogonadism, tall stature, gynecomastia. Mild mental retardation. Usually not diagnosed until after puberty. One Barr body seen on buccal smear.
Turner’s Syndrome (XO) ChromosomalSex chromosome Non-disjunction of the sex chromosome during Anaphase I of meiosis ——> Monosomy (45,X) Streak gonads, primary amenorrhea, webbed neck, short stature, coarctation of Aorta, infantile genitalia. No mental retardation. No Barr bodies visible on buccal smear.
XXX Syndrome ChromosomalSex chromosome Trisomy (47,XXX) and other multiple X-chromosome abnormalities. Usually phenotypically normal. May see menstrual abnormalities or mild mental retardation in some cases.
Ehlers-Danlos Syndrome Connective Tissue disease Various defects in collagen synthesis.

  • Type-I: Autosomal dominant, mildest form.
  • Type-IV: autosomal dominant. Defect in reticular collagen (type-III)
  • Type-VI: autosomal-recessive.
  • Type-VII: Defect in collagen type I
  • Type-IX: X-linked recessive
Laxity of joints, hyperextensibility of skin, poor wound healing, aneurysms.

  • 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 Connective tissue disease Defects in Collagen Type I formation. Multiple fractures after birth, blue sclerae, thin skin, progressive deafness in some types (due to abnormal middle ear ossicles).Type-I is most common;Type-II is most severe;Type-IV is mildest form.
Cori’s Disease(Glycogen Storage Disease Type III) Glycogen Storage Disease Autosomal Recessive. Debranching enzyme deficiency (can only break down linear chains of glycogen, not at branch points) ——> accumulate glycogen in liver, heart, skeletal muscle. Stunted growth, hepatomegaly, hypoglycemia.
McArdle’s Disease(Glycogen Storage Disease Type V) Glycogen Storage Disease Autosomal Recessive. muscle phosphorylase deficiency (cannot utilize glycogen in skeletal muscle) ——> accumulation of glycogen in skeletal muscle. Muscle cramps, muscle weakness, easy fatigability. Myoglobinuria with strenuous exercise.
Pompe’s Disease(Glycogen Storage Disease Type II) Glycogen Storage Disease Autosomal Recessive. alpha-1,4-Glucosidase deficiency (cannot break down glycogen) ——> accumulate glycogen in liver, heart, skeletal muscle. Cardiomegaly, hepatomegaly, and systemic findings, leading to early death.
Von Gierke’s Disease(Glycogen Storage Disease Type I) Glycogen Storage Disease Autosomal Recessive. Glucose-6-Phosphatase deficiency (cannot break down glycogen) ——> accumulate glycogen in liver and kidney. Severe fastinghypoglycemia, hepatomegaly from lots of glycogen in liver.
Hemophilia A (Factor VIII Deficiency) Hemophilia X-Linked Recessive. Factor VIII deficiency Hemorrhage, hematuria, hemarthroses. Prolonged PTT.
Hemophilia B (Factor IX Deficiency) Hemophilia X-Linked Recessive. Factor IX deficiency. Milder than Hemophilia A. Hemorrhage, hematuria, hemarthroses. Prolonged PTT.
Von Willebrand Disease Hemophilia Autosomal dominant and recessive varieties. Von Willebrand Factor deficiency ——> defect in initial formation of platelet plugs, and shorter half-life of Factor VIII in blood. Hemorrhage, similar to hemophilia.Type-I: Most mild. Type-II: Intermediate. Type-III: most severe, with recessive inheritance (complete absence).
Ataxia-Telangiectasia Immune deficiencyCombined Deficiency Autosomal Recessive. Unknown. Numerous chromosomal breaks and elevated AFP is found. Symptomatic by age 2 years. Cerebellar ataxia, telangiectasia (enlarged capillaries of face and skin), B and T-Cell deficiencies, IgA deficiency.
Chédiak-Higashi Syndrome Immune deficiencyPhagocyte Deficiency Defect in polymerization of microtubules in neutrophils ——> failure in neutrophil migration and phagocytosis. Also results in failure in lysosomal function in neutrophils. Recurrent pyogenic infections, Staphylococcus, Streptococcus.
Chronic Granulomatous Disease Immune deficiencyPhagocyte Deficiency X-Linked (usually) NADPH Oxidase deficiency ——> no formation of peroxides and superoxides ——> no oxidative burst in phagocytes. Failure of phagocytes leads to susceptibility to infections, especially Staph Aureus and Aspergillus spp. B and T cells usually remain normal.
Chronic Mucocutaneous Candidiasis Immune deficiencyT-Cell Deficiency T-Cell deficiency specific to Candida. Selective recurrentCandida infections. Treat with anti-fungal drugs.
Job’s Syndrome Immune deficiencyPhagocyte Deficiency A failure to produce gamma-Interferon by T-Helper cells, leading to an increase in TH2 cells (no negative feedback) ——> excessively high levels of IgE. High histamine levels, eosinophilia. Recurrentcold (non-inflammatory) Staphylococcal abscesses(resulting from high histamine), eczema.
Selective IgA Deficiency Immune deficiencyB-Cell Deficiency IgA deficiency may be due to a failure of heavy-chain gene switching. The most common congenital immune deficiency.  There also exists selective IgM and IgG deficiencies, but they are less common.
Severe Combined Immunodeficiency (SCID) Immune deficiencyCombined Deficiency Autosomal Recessive. Adenosine Deaminase deficiency ——> accumulation of dATP ——> inhibit ribonucleotide reductase ——> decrease in DNA precursors Severe deficiency in both humoral and cellular immunity, due to impaired DNA synthesis. Bone marrow transplant may be helpful in treatment.
Thymic Aplasia (DiGeorge Syndrome) Immune deficiencyT-Cell Deficiency Failure of development of the 3rd and 4th Pharyngeal Pouches ——> agenesis of the thymus and parathyroid glands. T-Cell deficiency from no thymus. Hypocalcemic tetany from primary parathyroid deficiency.
Wiskott-Aldrich Syndrome Immune deficiencyCombined Deficiency Inability to mount initial IgM response to the capsular polysaccharides of pyogenic bacteria. In infancy, recurrent pyogenic infections, eczema, thrombocytopenia, excessive bleeding. IgG levels remain normal.
X-Linked Agammaglobulinemia (Bruton’s Disease) Immune deficiencyB-Cell Deficiency X-Linked. Mutation in gene coding for tyrosine kinase causes failure of Pre-B cells to differentiate into B-Cells. Recurrent pyogenic infections after 6 months (when maternal antibodies wear off). Can treat with polyspecific gamma globulin preparations.
Fabry’s Disease Lysosomal Storage Disease X-Linked Recessive. alpha-Galactosidase A deficiency ——> buildup of ceramide trihexosidein body tissues. Angiokeratomas (skin lesions) over lower trunk, fever, severe burning pain in extremities, cardiovascular and cerebrovascular involvement.
Gaucher’s Disease Lysosomal Storage Disease Autosomal Recessive. Glucocerebrosidase deficiency ——> accumulation of glucocerebrosides (gangliosides, sphingolipids) in lysosomes throughout the body.
  • 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. Sphingomyelinase deficiency ——> accumulation of sphingomyelin in phagocytes. Sphingomyelin-containingfoamy histiocytes in reticuloendo-thelial system and spleen. Hepatosplenomegaly, anemia, fever, sometimes CNS deterioration. Death by age 3.
Hunter’s Syndrome Lysosomal Storage Disease X-Linked RecessiveL-iduronosulfate sulfatase deficiency ——> buildup ofmucopolysaccharides (heparan sulfate and dermatan sulfate) Similar to but less severe than Hurler Syndrome. Hepatosplenomegaly, micrognathia, retinal degeneration, joint stiffness, mild retardation, cardiac lesions.
Hurler’s Syndrome Lysosomal Storage Disease Autosomal Recessive. alpha-L-iduronidase deficiency ——> accumulation ofmucopolysaccharides (heparan sulfate, dermatan sulfate) in heart, brain, liver, other organs. Gargoyle-like facies, progressive mental deterioration, stubby fingers, death by age 10. Similar to Hunter’s Syndrome.
Tay-Sachs Disease Lysosomal Storage Disease Autosomal Recessive. Hexosaminidase A deficiency ——> accumulation of GM2 ganglioside in neurons. CNS degeneration, retardation, cherry red-spot of macula, blindness (amaurosis). Death before age 4.
Albinism Nitrogen Metabolism Defect Autosomal Recessive. Tyrosinase deficiency ——> inability to synthesize melanin from tyrosine. Can result from a lack of migration of neural crest cells. Depigmentation, pink eyes, increased risk of skin cancer.
Alkaptonuria Nitrogen Metabolism Defect Autosomal Recessive. Homogentisic Oxidase deficiency (inability to metabolize Phe and Tyr) ——> buildup and urinary excretion of homogentisic acid. Urine turns dark and black on standing, ochronosis(dark pigmentation of fibrous and cartilage tissues), ochronotic arthritis, cardiac valve involvement. Disease is generally benign.
Homocystinuria Nitrogen Metabolism Defect Autosomal Recessive. Cystathionine synthase defect (either deficiency, or lost affinity for pyridoxine, Vit. B6) ——> buildup of homocystine and deficiency of cysteine. 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.
Lesch-Nyhan Syndrome Nitrogen Metabolism Defect X-Linked Recessive. Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT) deficiency ——> no salvage pathway for purine re-synthesis ——> buildup of purine metabolites Hyperuricemia (gout), mental retardation, self-mutilation (autistic behavior), choreoathetosis, spasticity.
Maple Syrup Urine Disease Nitrogen Metabolism Defect Autosomal Recessive. Deficiency of branched chain keto-acid decarboxylase ——> no degradation of branched-chain amino acids ——> buildup of isoleucine, valine, leucine. Severe CNS defects, mental retardation, death. Person smells like maple syrup or burnt sugar. Treatment: remove the amino acids from diet.
Phenylketonuria (PKU) Nitrogen Metabolism Defect 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. 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.
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency RBC Disease X-Linked Recessive. Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency ——> no hexose monophosphate shunt ——> deficiency in NADPH ——> inability to maintain glutathione in reduced form, in RBC’s 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.
Glycolytic enzyme deficiencies RBC Disease Autosomal Recessive. Defect in hexokinase, glucose-phosphate isomerase, aldolase, triose-phosphate isomerase, phosphate-glycerate kinase, or enolase. Any enzyme in glycolysis pathway. Hemolytic anemia results from any defect in the glycolysis pathway, as RBC’s depend on glycolysis for energy.
Autosomal Recessive Polycystic Kidney Disease (ARPKD) Renal Autosomal Recessive. Numerous, diffuse bilateral cysts formed in the collecting ducts. Associated with hepatic fibrosis.
Bartter’s Syndrome Renal Juxtaglomerular Cell Hyperplasia, leading to primary hyper-reninemia. Elevated renin and aldosterone, hypokalemic alkalosis. No hypertension.
Fanconi’s Syndrome Type I(Child-onset cystinosis) Renal Autosomal Recessive. Deficient resorption in proximal tubules. (1) Cystine deposition throughout body, cystinuria. (2) Defective tubular resorption leads to amino-aciduria, polyuria, glycosuria, chronic acidosis;Hypophosphatemia andVitamin-D-resistant Rickets.
Fanconi’s Syndrome II(Adult-onset) Renal Autosomal Recessive. Defective resorption in proximal tubules. Similar to Fanconi Syndrome Type I, but without the cystinosis. Adult onset osteomalacia, amino-aciduria, polyuria, glycosuria.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) RenalAutosomal Dominant Disorders Autosomal Dominant. Numerous, disparate, heterogenous renal cysts occurring bilaterally. Onset in adult life. Associated with liver cysts.



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  1. Student must read and learn this genetics disorder on human disease, before discuss in class

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