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
Fanconi Anemia Autosomal Recessive
congenital pancytopenia.
Meconium ileus (caused
by thick, mucoid
meconium), respiratory
bronchiectasis,
Pseudomonas pneumonia,
pancreatic insufficiency,
hypertonic (high Cl-
concentration) sweat.
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. 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
things.
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
sterility.
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
sources.
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
Weber-Rendu
Syndrome)
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,
too.
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
cortex.
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:

pheochromocytoma,
Wilms tumor,
Rhabdomyosarcoma,
leukemias.
Tuberous Sclerosis Autosomal Autosomal Dominant. Tubers (glial nodules),
Dominant seizures, mental
 Disorders retardation. Associated
with adenoma sebaceum
(facial lesion), myocardial
rhabdomyomas, renal
angiomyolipomas.
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
carcinoma.
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
gluconeogenesis.
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.
deficiency.
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
generations.
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
smear.
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
rupture
• Type-IX: X-linked aneurysms.
recessive
• Type-VI: Retinal
detachment,
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
ossicles).

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
PTT.
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
neutrophils.
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
normal.
Chronic Immune T-Cell deficiency specific to Selective recurrent
Mucocutaneous deficiency Candida. Candida infections. Treat
Candidiasis with anti-fungal drugs.
T-Cell
Deficiency
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.
 IgE.
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
capsular polysaccharides of
Combined pyogenic bacteria.
Deficiency
X-Linked Immune X-Linked. Mutation in gene
Agammaglobulinemia deficiency coding for tyrosine kinase
(Bruton's Disease) causes failure of Pre-B cells
B-Cell to differentiate into B-Cells.
Deficiency
Fabry's Disease Lysosomal X-Linked Recessive. alpha-
Storage Galactosidase A deficiency
Disease ------> buildup of ceramide
trihexoside in body tissues.
Gaucher's Disease Lysosomal Autosomal Recessive.
Storage Glucocerebrosidase
Disease deficiency ------>
accumulation of
glucocerebrosides
(gangliosides,
sphingolipids) in lysosomes
throughout the body.
pyogenic infections,
eczema,
thrombocytopenia,
excessive bleeding. IgG
levels remain normal.
Recurrent pyogenic
infections after 6 months
(when maternal antibodies
wear off). Can treat with
polyspecific gamma
globulin preparations.
Angiokeratomas (skin
lesions) over lower trunk,
fever, severe burning pain
in extremities,
cardiovascular and
cerebrovascular
involvement.
• Type-I: Adult
form. 80% of
cases, retain
partial activity.
Hepatosplenomeg
aly, 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 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
cells.
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
excretion of homogentisic
acid.
Homocystinuria Nitrogen Autosomal Recessive.
Metabolism Cystathionine synthase
Defect defect (either deficiency, or
lost affinity for pyridoxine,
Vit. B6) ------> buildup of
homocystine and deficiency
of cysteine.
Lesch-Nyhan Nitrogen X-Linked Recessive.
Syndrome Metabolism Hypoxanthine-Guanine
Defect Phosphoribosyltransferase
(HGPRT) deficiency ------>
no salvage pathway for
purine re-synthesis ------>
buildup of purine
metabolites
Maple Syrup Urine Nitrogen Autosomal Recessive.
Disease Metabolism Deficiency of branched
Defect chain keto-acid
decarboxylase ------> no
degradation of branched-
chain amino acids ------>
buildup of isoleucine,
valine, leucine.
Phenylketonuria Nitrogen Autosomal Recessive.
(PKU) Metabolism Phenylalanine hydroxylase
Defect deficiency (cannot break
down Phe nor make Tyr)
------> buildup of
phenylalanine, phenyl
ketones (phenylacetate,
phenyl lactate,
phenylpyruvate) in body
tissues and CNS.
Glucose-6-Phosphate RBC Disease X-Linked Recessive.
Dehydrogenase Glucose-6-Phosphate
(G6PD) Deficiency Dehydrogenase (G6PD)
deficiency ------> no hexose
monophosphate shunt ------
> deficiency in NADPH
and cartilage tissues),
ochronotic arthritis,
cardiac valve
involvement. Disease is
generally benign.
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.
Hyperuricemia (gout),
mental retardation, self-
mutilation (autistic
behavior),
choreoathetosis,
spasticity.
Severe CNS defects,
mental retardation, death.
Person smells like maple
syrup or burnt sugar.
Treatment: remove the
amino acids from diet.
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.
Susceptibility to oxidative
damage to RBC's, leading
to hemolytic anemia.
Can be elicited by drugs
(primaquine,
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
fibrosis.
Bartter's Syndrome Renal Juxtaglomerular Cell Elevated renin and
Hyperplasia, leading to aldosterone, hypokalemic
primary hyper-reninemia. alkalosis. No
hypertension.
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
acidosis;
Hypophosphatemia and
Vitamin-D-resistant
Rickets.
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,
glycosuria.
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
cysts.