| 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 crease, brushfield spots in eyes. Associated syndromes: congenital heart disease, leukemia,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.
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Laxity of joints, hyperextensibility of skin, poor wound healing, aneurysms.
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| 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. |
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| 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 Recessive. L-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. |
TABLE of GENETIC DISORDERS PDF
Ref.
http://www.kumc.edu/AMA-MSS/Study/table_of_genetic_disorders.htm
https://www.genome.gov/10001204/specific-genetic-disorders/