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Disease Category Pathogenesis / Heredity Pathology, Cardinal Symptoms
Cystic Fibrosis Autosomal Recessive. CFTR gene Meconium ileus (caused by thick,
defect on Chrom 7 ------> No Cl- mucoid meconium), respiratory
transport and failure to hydrate bronchiectasis, Pseudomonas
mucous secretions (no NaCl pneumonia, pancreatic
transport) ------> excessively insufficiency, hypertonic (high
viscous mucoid exocrine secretions Cl- concentration) sweat.
Fanconi Anemia Autosomal Recessive congenital Normocytic anemia with
pancytopenia. 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 Pellagra-like syndrome (diarrhea,
uptake of neutral amino acids dementia, dermatitis), light-
------> malabsorption of sensitive skin rash, temporary
tryptophan (niacin precursor) cerebellar ataxia.
------> niacin deficiency among
other things.
Kartagener's Autosomal Recessive. Defect in Recurrent sinopulmonary
Syndrome dynein arms ------> lost motility of infections (due to impaired
cilia 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 Autosomal Recessive. Pyruvate Neurologic defects.
Dehydrogenase Dehydrogenase deficiency ------>
Deficiency buildup of lactate and pyruvate Treatment: Increase intake of
------> lactic acidosis. ketogenic nutrients (leucine,
lysine) ------> increase formation
of Acetyl-CoA from other
Xeroderma Autosomal Recessive. Defect in Dry skin, melanomas, pre-
Pigmentosum DNA repair, inability to repair malignant lesions, other cancers.
thymine dimers resulting from Ophthalmic and neurologic
UV-light exposure ------> abnormalities.
excessive skin damage and skin
Familial Autosomal A group of inherited diseases Heterozygous: accelerated
Hypercholesterolemia Dominant associated with atherosclerosis. Homozygous:
Disorders hypercholestrolemia. accelerated atherosclerosis, MI
by age 35, xanthomas.
Hereditary Autosomal Autosomal Dominant. Telangiectasias of skin and
Hemorrhagic Dominant mucous membranes.
Telangiectasia (Osler- Disorders
Hereditary Autosomal Autosomal Dominant. Band-3 Sequestration of spherocytes in
Spherocytosis Dominant deficiency in RBC membrane spleen ------> hemolytic anemia.
Disorders ------> spherical shape to cells.
Other RBC structural enzyme
deficiencies can cause it, too.
Huntington's Disease Autosomal Autosomal Dominant, 100% Progressive dementia with onset
Dominant penetrance. in adulthood, choreiform
Disorders movements, athetosis.
Genetic defect on Chrom 4 ------>
atrophy of caudate nuclei, putamen,
frontal cortex.
Marfan's Syndrome Autosomal Autosomal Dominant. Fibrillin Arachnodactyly, dissecting aortic
Dominant deficiency ------> faulty scaffolding aneurysms, ectopia lentis
Disorders in connective tissue (elastin has no (subluxation of lens), mitral valve
anchor). prolapse.
Neurofibromatosis Autosomal Autosomal Dominant. NF1 gene Multiple neurofibromas (Caf�
(Von Recklinghausen Dominant defect (no GTPase protein) ------> au Lait spots) which may become
Disease) Disorders dysregulation of Ras tumor- malignant, Lisch nodules
suppressor protein. (pigmented hamartomas of the

Increased risk for tumors:
pheochromocytoma, Wilms
tumor, Rhabdomyosarcoma,
Tuberous Sclerosis Autosomal Autosomal Dominant. Tubers (glial nodules), seizures,
Dominant mental retardation. Associated
Disorders with adenoma sebaceum (facial
lesion), myocardial
rhabdomyomas, renal
Von Hippel-Lindau Autosomal Autosomal Dominant, short arm of (1) Hemangioblastomas of
Syndrome Dominant chromosome 3. Same genetic cerebellum, medulla, or retina,
Disorders region is associated with incidence (2) adenomas, (3) cysts in
of renal cell carcinoma. visceral organs. High risk for
renal cell carcinoma.
Congenital Fructose Carbohydrate Autosomal Recessive. Aldolase B Severe hypoglycemia.
Intolerance Metabolism deficiency ------> buildup of Treatment: Remove fructose from
Defect Fructose-1-Phosphate in tissues diet.
------> inhibit glycogenolysis and
Galactosemia Carbohydrate Autosomal Recessive. Inability to Failure to thrive, infantile
Metabolism convert galactose to glucose ------> cataracts, mental retardation.
Defect accumulation of galactose in many Progressive hepatic failure,
tissues. cirrhosis, death.

(1) Classic form: Galactose-1- Galactokinase-deficiency:
phosphate Uridyltransferase infantile cataracts are prominent.
Treatment: in either case, remove
(2) Rarer form: Galactokinase galactose from diet.
Angelman Syndrome Chromosomal Deletion of part of short arm of Mental retardation, ataxic gait,
chromosome 15, maternal copy. seizures. Inappropriate
An example of genomic laughter.
Cri du Chat Chromosomal 5p-, deletion of the long arm of "Cry of the cat." Severe mental
Syndrome chromosome 5. retardation, microcephaly, cat-
like cry. Low birth-weight,
round-face, hypertelorism (wide-
set eyes), low-set ears, epicanthal
Down Syndrome Chromosomal Trisomy 21, with risk increasing Most common cause of mental
with maternal age. Familial form retardation. Will see epicanthal
(Trisomy 21) (no age-associated risk) is folds, simian crease, brushfield
translocation t(21,x) in a minority spots in eyes. Associated
of cases. syndromes: congenital heart
disease, leukemia, premature
Alzheimer's disease (same
morphological changes).
Edward's Syndrome Chromosomal Trisomy 18 Mental retardation, micrognathia,
rocker-bottom feet, congenital
(Trisomy 18) heart disease, flexion deformities
of fingers. Death by 1 year old.
Patau's Syndrome Chromosomal Trisomy 13 Mental retardation,
microphthalmia, cleft lip and
(Trisomy 13) palate, polydactyly, rocker-
bottom feet, congenital heart
disease. Similar to and more
severe than Edward's Syndrome.
Death by 1 year old.
Prader-Willi Chromosomal Deletion of part of short arm of Mental retardation, short stature,
Syndrome chromosome 15, paternal copy. hypotonia, obesity and huge
An example of genomic appetite after infancy. Small
imprinting. hands and feet, hypogonadism.
Fragile-X Syndrome Chromosomal Progressively longer tandem Second most common cause of
repeats on the long arm of the X- mental retardation next to
Sex chromosome. The longer the Down Syndrome. Macro-
chromosome number of repeats, the worse the orchidism (enlarged testes) in
syndrome. Tandem repeats tend to males.
accumulate through generations.
Klinefelter's Chromosomal Non-disjunction of the sex Hypogonadism, tall stature,
Syndrome (XXY) chromosome during Anaphase I of gynecomastia. Mild mental
Sex meiosis ------> Trisomy (47,XXY) retardation. Usually not
chromosome diagnosed until after puberty.
One Barr body seen on buccal
Turner's Syndrome Chromosomal Non-disjunction of the sex Streak gonads, primary
(XO) chromosome during Anaphase I of amenorrhea, webbed neck, short
Sex meiosis ------> Monosomy (45,X) stature, coarctation of Aorta,
chromosome infantile genitalia. No mental
retardation. No Barr bodies
visible on buccal smear.
XXX Syndrome Chromosomal Trisomy (47,XXX) and other Usually phenotypically normal.
multiple X-chromosome May see menstrual abnormalities
Sex abnormalities. or mild mental retardation in
chromosome some cases.

Ehlers-Danlos Connective Various defects in collagen Laxity of joints,
Syndrome Tissue disease synthesis. hyperextensibility of skin, poor
wound healing, aneurysms.
• Type-I: Autosomal
dominant, mildest form. • Type-I: Diaphragmatic
• Type-IV: autosomal hernia. Common, normal
dominant. Defect in life-expectancy.
reticular collagen (type-III) • Type-IV: Ecchymoses,
• Type-VI: autosomal- arterial rupture.
recessive. Dangerous due to rupture
• Type-VII: Defect in aneurysms.
collagen type I
• Type-VI: Retinal
• Type-IX: X-linked detachment, corneal
recessive rupture
Osteogenesis Connective Defects in Collagen Type I Multiple fractures after birth,
Imperfecta tissue disease formation. 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 Autosomal Recessive. Stunted growth, hepatomegaly,
Storage Debranching enzyme deficiency hypoglycemia.
(Glycogen Storage Disease (can only break down linear chains
Disease Type III) of glycogen, not at branch points)
------> accumulate glycogen in
liver, heart, skeletal muscle.
McArdle's Disease Glycogen Autosomal Recessive. muscle Muscle cramps, muscle
Storage phosphorylase deficiency (cannot weakness, easy fatigability.
(Glycogen Storage Disease utilize glycogen in skeletal muscle) Myoglobinuria with strenuous
Disease Type V) ------> accumulation of glycogen in exercise.
skeletal muscle.
Pompe's Disease Glycogen Autosomal Recessive. alpha-1,4- Cardiomegaly, hepatomegaly,
Storage Glucosidase deficiency (cannot and systemic findings, leading to
(Glycogen Storage Disease break down glycogen) ------> early death.
Disease Type II) accumulate glycogen in liver, heart,
skeletal muscle.
Von Gierke's Disease Glycogen Autosomal Recessive. Glucose-6- Severe fasting hypoglycemia,
Storage Phosphatase deficiency (cannot hepatomegaly from lots of
(Glycogen Storage Disease break down glycogen) ------> glycogen in liver.
Disease Type I) accumulate glycogen in liver and
Hemophilia A (Factor Hemophilia X-Linked Recessive. Factor VIII Hemorrhage, hematuria,
VIII Deficiency) deficiency hemarthroses. Prolonged PTT.
Hemophilia B (Factor Hemophilia X-Linked Recessive. Factor IX Milder than Hemophilia A.
IX Deficiency) deficiency. Hemorrhage, hematuria,
hemarthroses. Prolonged PTT.
Von Willebrand Hemophilia Autosomal dominant and recessive Hemorrhage, similar to
Disease varieties. Von Willebrand Factor hemophilia.
deficiency ------> defect in initial
formation of platelet plugs, and Type-I: Most mild. Type-II:
shorter half-life of Factor VIII in Intermediate. Type-III: most
blood. severe, with recessive inheritance
(complete absence).
Ataxia-Telangiectasia Immune Autosomal Recessive. Unknown. Cerebellar ataxia, telangiectasia
deficiency Numerous chromosomal breaks and (enlarged capillaries of face and
elevated AFP is found. skin), B and T-Cell deficiencies,
Combined Symptomatic by age 2 years. IgA deficiency.
Ch�diak-Higashi Immune Defect in polymerization of Recurrent pyogenic infections,
Syndrome deficiency microtubules in neutrophils ------> Staphylococcus, Streptococcus.
failure in neutrophil migration and
Phagocyte phagocytosis. Also results in failure
Deficiency in lysosomal function in
Chronic Immune X-Linked (usually) NADPH Failure of phagocytes leads to
Granulomatous deficiency Oxidase deficiency ------> no susceptibility to infections,
Disease formation of peroxides and especially Staph Aureus and
Phagocyte superoxides ------> no oxidative Aspergillus spp. B and T cells
Deficiency burst in phagocytes. usually remain normal.

Chronic Immune T-Cell deficiency specific to Selective recurrent Candida
Mucocutaneous deficiency Candida. infections. Treat with anti-fungal
Candidiasis drugs.
Job's Syndrome Immune A failure to produce gamma- High histamine levels,
deficiency Interferon by T-Helper cells, eosinophilia. Recurrent cold
leading to an increase in TH2 cells (non-inflammatory)
Phagocyte (no negative feedback) ------> Staphylococcal abscesses
Deficiency excessively high levels of IgE. (resulting from high histamine),
Selective IgA Immune IgA deficiency may be due to a The most common congenital
Deficiency deficiency failure of heavy-chain gene immune deficiency. There also
switching. exists selective IgM and IgG
B-Cell deficiencies, but they are less
Deficiency common.

Severe Combined Immune Autosomal Recessive. Adenosine Severe deficiency in both
Immunodeficiency deficiency Deaminase deficiency ------> humoral and cellular immunity,
(SCID) accumulation of dATP ------> due to impaired DNA synthesis.
Combined inhibit ribonucleotide reductase Bone marrow transplant may be
Deficiency ------> decrease in DNA precursors helpful in treatment.

Thymic Aplasia Immune Failure of development of the 3rd T-Cell deficiency from no
(DiGeorge Syndrome) deficiency and 4th Pharyngeal Pouches thymus. Hypocalcemic tetany
------> agenesis of the thymus and from primary parathyroid
T-Cell parathyroid glands. deficiency.
Wiskott-Aldrich Immune Inability to mount initial IgM In infancy, recurrent pyogenic
Syndrome deficiency response to the capsular infections, eczema,
polysaccharides of pyogenic thrombocytopenia, excessive
Combined bacteria. bleeding. IgG levels remain
Deficiency normal.

X-Linked Immune X-Linked. Mutation in gene coding Recurrent pyogenic infections
Agammaglobulinemia deficiency for tyrosine kinase causes failure after 6 months (when maternal
(Bruton's Disease) of Pre-B cells to differentiate into antibodies wear off). Can treat
B-Cell B-Cells. with polyspecific gamma
Deficiency globulin preparations.

Fabry's Disease Lysosomal X-Linked Recessive. alpha- Angiokeratomas (skin lesions)
Storage Galactosidase A deficiency ------> over lower trunk, fever, severe
Disease buildup of ceramide trihexoside in burning pain in extremities,
body tissues. cardiovascular and
cerebrovascular involvement.
Gaucher's Disease Lysosomal Autosomal Recessive. • Type-I: Adult form. 80%
Storage Glucocerebrosidase deficiency of cases, retain partial
Disease ------> accumulation of activity.
glucocerebrosides (gangliosides, Hepatosplenomegaly,
sphingolipids) in lysosomes erosion of femoral head,
throughout the body. 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 Lysosomal Autosomal Recessive. Sphingomyelin-containing foamy
Lipidosis Storage Sphingomyelinase deficiency histiocytes in reticuloendo-thelial
Disease ------> accumulation of system and spleen.
sphingomyelin in phagocytes. Hepatosplenomegaly, anemia,
fever, sometimes CNS
deterioration. Death by age 3.
Hunter's Syndrome Lysosomal X-Linked Recessive. L- Similar to but less severe than
Storage iduronosulfate sulfatase Hurler Syndrome.
Disease deficiency ------> buildup of Hepatosplenomegaly,
mucopolysaccharides (heparan micrognathia, retinal
sulfate and dermatan sulfate) degeneration, joint stiffness, mild
retardation, cardiac lesions.
Hurler's Syndrome Lysosomal Autosomal Recessive. alpha-L- Gargoyle-like facies, progressive
Storage iduronidase deficiency ------> mental deterioration, stubby
Disease accumulation of fingers, death by age 10. Similar
mucopolysaccharides (heparan to Hunter's Syndrome.
sulfate, dermatan sulfate) in heart,
brain, liver, other organs.
Tay-Sachs Disease Lysosomal Autosomal Recessive. CNS degeneration, retardation,
Storage Hexosaminidase A deficiency cherry red-spot of macula,
Disease ------> accumulation of GM2 blindness (amaurosis). Death
ganglioside in neurons. before age 4.
Albinism Nitrogen Autosomal Recessive. Tyrosinase Depigmentation, pink eyes,
Metabolism deficiency ------> inability to increased risk of skin cancer.
Defect synthesize melanin from tyrosine.
Can result from a lack of migration
of neural crest cells.
Alkaptonuria Nitrogen Autosomal Recessive. Urine turns dark and black on
Metabolism Homogentisic Oxidase deficiency standing, ochronosis (dark
Defect (inability to metabolize Phe and pigmentation of fibrous and
Tyr) ------> buildup and urinary cartilage tissues), ochronotic
excretion of homogentisic acid. arthritis, cardiac valve
involvement. Disease is generally
Homocystinuria Nitrogen Autosomal Recessive. Mental retardation, ectopia lentis,
Metabolism Cystathionine synthase defect sparse blond hair, genu valgum,
Defect (either deficiency, or lost affinity failure to thrive, thromboembolic
for pyridoxine, Vit. B6) ------> episodes, fatty changes of liver.
buildup of homocystine and
deficiency of cysteine. Treatment: Cysteine
supplementation, give excess
pyridoxine to compensate for lost
pyridoxine affinity.
Lesch-Nyhan Nitrogen X-Linked Recessive. Hyperuricemia (gout), mental
Syndrome Metabolism Hypoxanthine-Guanine retardation, self-mutilation
Defect Phosphoribosyltransferase (autistic behavior),
(HGPRT) deficiency ------> no choreoathetosis, spasticity.
salvage pathway for purine re-
synthesis ------> buildup of purine
Maple Syrup Urine Nitrogen Autosomal Recessive. Deficiency Severe CNS defects, mental
Disease Metabolism of branched chain keto-acid retardation, death. Person smells
Defect decarboxylase ------> no like maple syrup or burnt sugar.
degradation of branched-chain Treatment: remove the amino
amino acids ------> buildup of acids from diet.
isoleucine, valine, leucine.
Phenylketonuria Nitrogen Autosomal Recessive. Symptoms result from
(PKU) Metabolism Phenylalanine hydroxylase accumulation of phenylalanine
Defect deficiency (cannot break down Phe itself. Mental deterioration,
nor make Tyr) ------> buildup of hypopigmentation (blond hair
phenylalanine, phenyl ketones and blue eyes), mousy body odor
(phenylacetate, phenyl lactate, (from phenylacetic acid in urine
phenylpyruvate) in body tissues and and sweat).
Treatment: remove phenylalanine
from diet.
Glucose-6-Phosphate RBC Disease X-Linked Recessive. Glucose-6- Susceptibility to oxidative
Dehydrogenase Phosphate Dehydrogenase damage to RBC's, leading to
(G6PD) Deficiency (G6PD) deficiency ------> no hemolytic anemia. Can be
hexose monophosphate shunt elicited by drugs (primaquine,
------> deficiency in NADPH sulfonamides, aspirin), fava
------> inability to maintain beans (favism). More prevalent
glutathione in reduced form, in in blacks.
Glycolytic enzyme RBC Disease Autosomal Recessive. Defect in Hemolytic anemia results from
deficiencies hexokinase, glucose-phosphate any defect in the glycolysis
isomerase, aldolase, triose- pathway, as RBC's depend on
phosphate isomerase, phosphate- glycolysis for energy.
glycerate kinase, or enolase. Any
enzyme in glycolysis pathway.
Autosomal Recessive Renal Autosomal Recessive. Numerous, diffuse bilateral cysts
Polycystic Kidney formed in the collecting ducts.
Disease (ARPKD) Associated with hepatic fibrosis.
Bartter's Syndrome Renal Juxtaglomerular Cell Hyperplasia, Elevated renin and aldosterone,
leading to primary hyper- hypokalemic alkalosis. No
reninemia. hypertension.
Fanconi's Syndrome Renal Autosomal Recessive. Deficient (1) Cystine deposition throughout
Type I resorption in proximal tubules. body, cystinuria. (2) Defective
tubular resorption leads to amino-
(Child-onset aciduria, polyuria, glycosuria,
cystinosis) chronic acidosis;
Hypophosphatemia and
Vitamin-D-resistant Rickets.
Fanconi's Syndrome Renal Autosomal Recessive. Defective Similar to Fanconi Syndrome
II resorption in proximal tubules. Type I, but without the
cystinosis. Adult onset
(Adult-onset) osteomalacia, amino-aciduria,
polyuria, glycosuria.
Autosomal Dominant Renal Autosomal Dominant. Numerous, disparate,
Polycystic Kidney heterogenous renal cysts
Disease (ADPKD) Autosomal occurring bilaterally. Onset in
Dominant adult life. Associated with liver
Disorders cysts.