| 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 of tryptophan (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 from UV-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 |
A group of inherited diseases associated with hypercholestrolemia. |
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 |
Chromosomal
Sex 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) |
Chromosomal
Sex 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) |
Chromosomal
Sex 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 |
Chromosomal
Sex 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.
Dangerous due 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 fasting hypoglycemia, 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 deficiency
Combined 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 deficiency
Phagocyte 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 deficiency
Phagocyte 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 deficiency
T-Cell Deficiency
|
T-Cell deficiency specific to Candida. |
Selective recurrent Candida infections. Treat with
anti-fungal drugs. |
| Job's Syndrome |
Immune deficiency
Phagocyte 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. Recurrent cold
(non-inflammatory) Staphylococcal abscesses
(resulting from high histamine), eczema. |
| Selective IgA Deficiency |
Immune deficiency
B-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 deficiency
Combined 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 deficiency
T-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 deficiency
Combined 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 deficiency
B-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 trihexoside in 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-containing foamy 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 of mucopolysaccharides
(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 of mucopolysaccharides (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 and
Vitamin-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) |
Renal
Autosomal Dominant Disorders
|
Autosomal Dominant. |
Numerous, disparate, heterogenous renal cysts occurring bilaterally.
Onset in adult life. Associated with liver cysts. |
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