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Disease Category Pathogenesis / Heredity Pathology, Cardinal

Cystic Fibrosis Autosomal Recessive. Meconium ileus (caused
CFTR gene defect on by thick, mucoid
Chrom 7 ------> No Cl- meconium), respiratory
transport and failure to bronchiectasis,
hydrate mucous secretions Pseudomonas pneumonia,
(no NaCl transport) ------> pancreatic insufficiency,
excessively viscous mucoid hypertonic (high Cl-
exocrine secretions concentration) sweat.
Fanconi Anemia Autosomal Recessive Normocytic anemia with
congenital pancytopenia. neutropenia.

Short stature,
strabismus, anomalies of
the thumbs, radii, and
kidneys, mental
retardation, and
Hartnup's Disease Autosomal Recessive. Pellagra-like syndrome
Defect in GI uptake of (diarrhea, dementia,
neutral amino acids ------> dermatitis), light-sensitive
malabsorption of skin rash, temporary
tryptophan (niacin cerebellar ataxia.
precursor) ------> niacin
deficiency among other
Kartagener's Autosomal Recessive. Recurrent
Syndrome Defect in dynein arms ------ sinopulmonary
> lost motility of cilia 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
Pyruvate Autosomal Recessive. Neurologic defects.
Dehydrogenase Pyruvate Dehydrogenase
Deficiency deficiency ------> buildup of Treatment: Increase intake
lactate and pyruvate ------> of ketogenic nutrients
lactic acidosis. (leucine, lysine) ------>
increase formation of
Acetyl-CoA from other
Xeroderma Autosomal Recessive. Dry skin, melanomas, pre-
Pigmentosum Defect in DNA repair, malignant lesions, other
inability to repair thymine cancers. Ophthalmic and
dimers resulting from UV- neurologic abnormalities.
light exposure ------>
excessive skin damage and
skin cancer.
Familial Autosomal Autosomal Dominant. LDL- Heterozygous: accelerated
Hypercholesterolemia Dominant Receptor defect. atherosclerosis.
Disorders Homozygous: accelerated
atherosclerosis, MI by age
35, xanthomas.
Hereditary Autosomal Autosomal Dominant. Telangiectasias of skin
Hemorrhagic Dominant and mucous membranes.
Telangiectasia (Osler- Disorders
Hereditary Autosomal Autosomal Dominant. Sequestration of
Spherocytosis Dominant Band-3 deficiency in RBC spherocytes in spleen
Disorders membrane ------> spherical ------> hemolytic anemia.
shape to cells. Other RBC
structural enzyme
deficiencies can cause it,
Huntington's Disease Autosomal Autosomal Dominant, Progressive dementia with
Dominant 100% penetrance. onset in adulthood,
Disorders choreiform movements,
Genetic defect on Chrom 4 athetosis.
------> atrophy of caudate
nuclei, putamen, frontal
Marfan's Syndrome Autosomal Autosomal Dominant. Arachnodactyly,
Dominant Fibrillin deficiency ------> dissecting aortic
Disorders faulty scaffolding in aneurysms, ectopia lentis
connective tissue (elastin (subluxation of lens),
has no anchor). mitral valve prolapse.
Neurofibromatosis Autosomal Autosomal Dominant. NF1 Multiple neurofibromas
(Von Recklinghausen Dominant gene defect (no GTPase (Café au Lait spots) which
Disease) Disorders protein) ------> may become malignant,
dysregulation of Ras tumor- Lisch nodules
suppressor protein. (pigmented hamartomas
of the iris).

Increased risk for tumors:

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

(1) Classic form: Galactose- Galactokinase-deficiency:

1-phosphate infantile cataracts are
Uridyltransferase prominent.
Treatment: in either case,
(2) Rarer form: remove galactose from
Galactokinase deficiency. diet.
Angelman Syndrome Chromosomal Deletion of part of short arm Mental retardation, ataxic
of chromosome 15, gait, seizures.
maternal copy. An example Inappropriate laughter.
of genomic imprinting.
Cri du Chat Chromosomal 5p-, deletion of the long arm "Cry of the cat." Severe
Syndrome of chromosome 5. mental retardation,
microcephaly, cat-like cry.
Low birth-weight, round-
face, hypertelorism (wide-
set eyes), low-set ears,
epicanthal folds.
Down Syndrome Chromosomal Trisomy 21, with risk Most common cause of
increasing with maternal mental retardation. Will
(Trisomy 21) age. Familial form (no age- see epicanthal folds,
associated risk) is simian crease, brushfield
translocation t(21,x) in a spots in eyes. Associated
minority of cases. syndromes: congenital
heart disease, leukemia,
premature Alzheimer's
disease (same
morphological changes).
Edward's Syndrome Chromosomal Trisomy 18 Mental retardation,
micrognathia, rocker-
(Trisomy 18) bottom feet, congenital
heart disease, flexion
deformities of fingers.
Death by 1 year old.
Patau's Syndrome Chromosomal Trisomy 13 Mental retardation,
microphthalmia, cleft lip
(Trisomy 13) 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 Chromosomal Deletion of part of short arm Mental retardation, short
Syndrome of chromosome 15, stature, hypotonia, obesity
paternal copy. An example and huge appetite after
of genomic imprinting. infancy. Small hands and
feet, hypogonadism.
Fragile-X Syndrome Chromosomal Progressively longer Second most common
tandem repeats on the long cause of mental
Sex arm of the X-chromosome. retardation next to Down
chromosome The longer the number of Syndrome. Macro-
repeats, the worse the orchidism (enlarged
syndrome. Tandem repeats testes) in males.
tend to accumulate through
Klinefelter's Chromosomal Non-disjunction of the sex Hypogonadism, tall
Syndrome (XXY) chromosome during stature, gynecomastia.
Sex Anaphase I of meiosis ------ Mild mental retardation.
chromosome > Trisomy (47,XXY) Usually not 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 amenorrhea, webbed
Sex Anaphase I of meiosis ------ neck, short stature,
chromosome > Monosomy (45,X) coarctation of Aorta,
infantile genitalia. No
mental retardation. No
Barr bodies visible on
buccal smear.
XXX Syndrome Chromosomal Trisomy (47,XXX) and Usually phenotypically
other multiple X- normal. May see
Sex chromosome abnormalities. menstrual abnormalities
chromosome or mild mental retardation
in some cases.
Ehlers-Danlos Connective Various defects in collagen Laxity of joints,
Syndrome Tissue disease synthesis. hyperextensibility of skin,
poor wound healing,
• Type-I: Autosomal aneurysms.
dominant, mildest
form. • Type-I:
• Type-IV: autosomal Diaphragmatic
dominant. Defect in hernia. Common,
reticular collagen normal life-
(type-III) expectancy.
• Type-VI: autosomal- • Type-IV:
recessive. Ecchymoses,
• Type-VII: Defect in arterial rupture.
collagen type I Dangerous due to
• Type-IX: X-linked aneurysms.
• Type-VI: Retinal
corneal rupture
Osteogenesis Connective Defects in Collagen Type I Multiple fractures after
Imperfecta tissue disease formation. birth, blue sclerae, thin
skin, progressive deafness
in some types (due to
abnormal middle ear

Type-I is most common;

Type-II is most severe;
Type-IV is mildest form.
Cori's Disease Glycogen Autosomal Recessive. Stunted growth,
Storage Debranching enzyme hepatomegaly,
(Glycogen Storage Disease deficiency (can only break hypoglycemia.
Disease Type III) down linear chains of
glycogen, not at branch
points) ------> accumulate
glycogen in liver, heart,
skeletal muscle.
McArdle's Disease Glycogen Autosomal Recessive. Muscle cramps, muscle
Storage muscle phosphorylase weakness, easy
(Glycogen Storage Disease deficiency (cannot utilize fatigability.
Disease Type V) glycogen in skeletal muscle) Myoglobinuria with
------> accumulation of strenuous exercise.
glycogen in skeletal muscle.
Pompe's Disease Glycogen Autosomal Recessive. Cardiomegaly,
Storage alpha-1,4-Glucosidase hepatomegaly, and
(Glycogen Storage Disease deficiency (cannot break systemic findings, leading
Disease Type II) down glycogen) ------> to early death.
accumulate glycogen in
liver, heart, skeletal muscle.
Von Gierke's Disease Glycogen Autosomal Recessive. Severe fasting
Storage Glucose-6-Phosphatase hypoglycemia,
(Glycogen Storage Disease deficiency (cannot break hepatomegaly from lots of
down glycogen) ------> glycogen in liver.
Disease Type I) accumulate glycogen in
liver and kidney.
Hemophilia A (Factor Hemophilia X-Linked Recessive. Factor Hemorrhage, hematuria,
VIII Deficiency) VIII deficiency hemarthroses. Prolonged
Hemophilia B (Factor Hemophilia X-Linked Recessive. Factor Milder than Hemophilia
IX Deficiency) IX deficiency. A. Hemorrhage,
hematuria, hemarthroses.
Prolonged PTT.
Von Willebrand Hemophilia Autosomal dominant and Hemorrhage, similar to
Disease recessive varieties. Von hemophilia.
Willebrand Factor
deficiency ------> defect in Type-I: Most mild. Type-
initial formation of platelet II: Intermediate. Type-
plugs, and shorter half-life III: most severe, with
of Factor VIII in blood. recessive inheritance
(complete absence).
Ataxia-Telangiectasia Immune Autosomal Recessive. Cerebellar ataxia,
deficiency Unknown. Numerous telangiectasia (enlarged
chromosomal breaks and capillaries of face and
Combined elevated AFP is found. skin), B and T-Cell
Deficiency Symptomatic by age 2 deficiencies, IgA
years. deficiency.
Chédiak-Higashi Immune Defect in polymerization of Recurrent pyogenic
Syndrome deficiency microtubules in neutrophils infections,
------> failure in neutrophil Staphylococcus,
Phagocyte migration and phagocytosis. Streptococcus.
Deficiency Also results in failure in
lysosomal function in
Chronic Immune X-Linked (usually) NADPH Failure of phagocytes
Granulomatous deficiency Oxidase deficiency ------> leads to susceptibility to
Disease no formation of peroxides infections, especially
Phagocyte and superoxides ------> no Staph Aureus and
Deficiency oxidative burst in Aspergillus spp. B and T
phagocytes. cells usually remain
Chronic Immune T-Cell deficiency specific to Selective recurrent
Mucocutaneous deficiency Candida. Candida infections. Treat
Candidiasis with anti-fungal drugs.
Job's Syndrome Immune A failure to produce High histamine levels,
deficiency gamma-Interferon by T- eosinophilia. Recurrent
Helper cells, leading to an cold (non-inflammatory)
Phagocyte increase in TH2 cells (no Staphylococcal abscesses
Deficiency negative feedback) ------> (resulting from high
excessively high levels of histamine), eczema.
Selective IgA Immune IgA deficiency may be due The most common
Deficiency deficiency to a failure of heavy-chain congenital immune
gene switching. deficiency. There also
B-Cell exists selective IgM and
Deficiency IgG deficiencies, but they
are less common.
Severe Combined Immune Autosomal Recessive. Severe deficiency in both
Immunodeficiency deficiency Adenosine Deaminase humoral and cellular
(SCID) deficiency ------> immunity, due to impaired
Combined accumulation of dATP ------ DNA synthesis. Bone
Deficiency > inhibit ribonucleotide marrow transplant may be
reductase ------> decrease in helpful in treatment.
DNA precursors
Thymic Aplasia Immune Failure of development of T-Cell deficiency from no
(DiGeorge Syndrome) deficiency the 3rd and 4th Pharyngeal thymus. Hypocalcemic
Pouches ------> agenesis of tetany from primary
T-Cell the thymus and parathyroid parathyroid deficiency.
Deficiency glands.

Wiskott-Aldrich Immune Inability to mount initial In infancy, recurrent

Syndrome deficiency IgM response to the pyogenic infections,
capsular polysaccharides of eczema,
Combined pyogenic bacteria. thrombocytopenia,
Deficiency excessive bleeding. IgG
levels remain normal.
X-Linked Immune X-Linked. Mutation in gene Recurrent pyogenic
Agammaglobulinemia deficiency coding for tyrosine kinase infections after 6 months
(Bruton's Disease) causes failure of Pre-B cells (when maternal antibodies
B-Cell to differentiate into B-Cells. wear off). Can treat with
Deficiency polyspecific gamma
globulin preparations.
Fabry's Disease Lysosomal X-Linked Recessive. alpha- Angiokeratomas (skin
Storage Galactosidase A deficiency lesions) over lower trunk,
Disease ------> buildup of ceramide fever, severe burning pain
trihexoside in body tissues. in extremities,
cardiovascular and
Gaucher's Disease Lysosomal Autosomal Recessive. • Type-I: Adult
Storage Glucocerebrosidase form. 80% of
Disease deficiency ------> cases, retain
accumulation of partial activity.
glucocerebrosides Hepatosplenomeg
(gangliosides, aly, erosion of
sphingolipids) in lysosomes femoral head, mild
throughout the body. anemia. Normal
lifespan with
• Type-II: Infantile
form. Severe CNS
Death before age

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