Disease |
Category |
Pathogenesis / Heredity |
Pathology, Cardinal Symptoms |
Cystic Fibrosis |
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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 |
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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 |
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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 |
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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 |
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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 |
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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.
- 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
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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
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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. |
- 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.
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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. |