"PPG LISTS" © QUICK REVISION TABLES

SELECTED GENETIC DISORDERS

Disease Category Pathogenesis / Heredity Pathology, Cardinal

Symptoms
Cystic Fibrosis   Autosomal Recessive. Meconium ileus
CFTR gene defect on (caused by thick,
Chrom 7 ------> No Cl- mucoid meconium),
transport and failure to respiratory
hydrate mucous secretions bronchiectasis,
(no NaCl transport) ------> Pseudomonas
excessively viscous pneumonia, pancreatic
mucoid exocrine insufficiency,
secretions hypertonic (high Cl-
concentration) sweat.
Fanconi Anemia   Autosomal Recessive Normocytic anemia
congenital pancytopenia. 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-
malabsorption of sensitive skin rash,
tryptophan (niacin temporary cerebellar
precursor) ------> niacin ataxia.
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 Treatment: Increase intake of
Deficiency deficiency ------> buildup ketogenic nutrients (leucine,
of lactate and pyruvate
lysine) ------> increase
------> lactic acidosis.
formation of Acetyl-CoA from

other sources.

Xeroderma   Autosomal Recessive. Dry skin, melanomas,

Pigmentosum Defect in DNA repair, pre-malignant lesions,
inability to repair thymine other cancers.
dimers resulting from Ophthalmic and
UV-light exposure ------> neurologic
excessive skin damage and abnormalities.
skin cancer.
Familial Autosomal Autosomal Dominant. Heterozygous:
Hypercholesterolemi Dominant LDL-Receptor defect. accelerated
a Disorders atherosclerosis.
Homozygous:
accelerated
atherosclerosis, MI by
age 35, xanthomas.
Hereditary Autosomal Autosomal Dominant. Telangiectasias of skin
Hemorrhagic Dominant and mucous
Telangiectasia Disorders membranes.
(Osler-Weber-Rendu
Syndrome)
Hereditary Autosomal Autosomal Dominant. Sequestration of
Spherocytosis Dominant Band-3 deficiency in RBC spherocytes in spleen
Disorders membrane ------> ------> hemolytic
spherical shape to cells. anemia.
Other RBC structural
enzyme deficiencies can
cause it, too.
Huntington's Disease Autosomal Autosomal Dominant, Progressive dementia
Dominant 100% penetrance. with onset in adulthood,
Disorders Genetic defect on Chrom 4 ------> choreiform movements,
atrophy of caudate nuclei, putamen,
athetosis.
frontal cortex.

Marfan's Syndrome Autosomal Autosomal Dominant. Arachnodactyly,

Dominant Fibrillin deficiency ------> dissecting aortic
Disorders faulty scaffolding in aneurysms, ectopia
connective tissue (elastin lentis (subluxation of
has no anchor). lens), mitral valve
 prolapse.
Neurofibromatosis Autosomal Autosomal Dominant. Multiple neurofibromas
(Von Dominant NF1 gene defect (no (Café au Lait spots)
Recklinghausen Disorders GTPase protein) ------> which may become
Disease) dysregulation of Ras malignant, Lisch
tumor-suppressor protein. nodules (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, (1) Hemangioblastomas
Syndrome Dominant short arm of chromosome of cerebellum, medulla,
Disorders 3. Same genetic region is or retina, (2) adenomas,
associated with incidence (3) cysts in visceral
of renal cell carcinoma. organs. High risk for
renal cell carcinoma.
Congenital Fructose Carbohydrate Autosomal Recessive. Severe hypoglycemia.
Intolerance Metabolism Aldolase B deficiency Treatment: Remove
Defect ------> buildup of fructose from diet.
Fructose-1-Phosphate in
tissues ------> inhibit
glycogenolysis and
gluconeogenesis.
Galactosemia Carbohydrate Autosomal Recessive. Failure to thrive,
Metabolism Inability to convert infantile cataracts,
Defect galactose to glucose mental retardation.
------> accumulation of Progressive hepatic
galactose in many tissues. failure, cirrhosis, death.
(1) Classic form: Galactose-1- Galactokinase-deficiency:

phosphate Uridyltransferase infantile cataracts are

deficiency. prominent.

(2) Rarer form: Galactokinase Treatment: in either case,

deficiency. remove galactose from diet.

Angelman Syndrome Chromosoma Deletion of part of short Mental retardation,

 l arm of chromosome 15, ataxic gait, seizures.
maternal copy. An Inappropriate
example of genomic laughter.
imprinting.
Cri du Chat Chromosoma 5p-, deletion of the long "Cry of the cat." Severe
Syndrome l arm 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 Chromosoma Trisomy 21, with risk Most common cause of
(Trisomy 21) l increasing with maternal mental retardation. Will
age. Familial form (no see epicanthal folds,
age-associated risk) is simian crease,
translocation t(21,x) in a brushfield spots in
minority of cases. eyes. Associated
syndromes: congenital
heart disease,
leukemia, premature
Alzheimer's disease
(same morphological
changes).
Edward's Syndrome Chromosoma Trisomy 18 Mental retardation,
(Trisomy 18) l micrognathia, rocker-
bottom feet, congenital
heart disease, flexion
deformities of fingers.
Death by 1 year old.
Patau's Syndrome Chromosoma Trisomy 13 Mental retardation,
(Trisomy 13) l 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 Chromosoma Deletion of part of short Mental retardation,
Syndrome l arm of chromosome 15, short stature, hypotonia,
paternal copy. An obesity and huge
example of genomic appetite after infancy.
imprinting. Small hands and feet,
hypogonadism.
Fragile-X Syndrome Chromosoma Progressively longer Second most common
l tandem repeats on the cause of mental
Sex chromosome long arm of the X- retardation next to
chromosome. The longer Down Syndrome.
the number of repeats, the Macro-orchidism
worse the syndrome. (enlarged testes) in
Tandem repeats tend to males.
accumulate through
generations.
Klinefelter's Chromosoma Non-disjunction of the sex Hypogonadism, tall
Syndrome (XXY) l chromosome during stature, gynecomastia.
Sex chromosome Anaphase I of meiosis Mild mental retardation.
------> Trisomy (47,XXY) Usually not diagnosed
until after puberty. One
Barr body seen on
buccal smear.
Turner's Syndrome Chromosoma Non-disjunction of the sex Streak gonads, primary
(XO) l chromosome during amenorrhea, webbed
Sex chromosome Anaphase I of meiosis neck, short stature,
------> Monosomy (45,X) coarctation of Aorta,
infantile genitalia. No
mental retardation. No
Barr bodies visible on
buccal smear.
XXX Syndrome Chromosoma Trisomy (47,XXX) and Usually phenotypically
l other multiple X- normal. May see
Sex chromosome chromosome menstrual abnormalities
abnormalities. or mild mental
retardation in some
cases.
Ehlers-Danlos Connective Various defects in Laxity of joints,
Syndrome Tissue collagen synthesis. hyperextensibility of
disease skin, poor wound
 Type-I: Autosomal healing, aneurysms.
dominant, mildest
form.  Type-I:
 Type-IV: Diaphragmatic
autosomal hernia.
dominant. Defect Common,
in reticular normal life-
collagen (type-III) expectancy.
 Type-VI:  Type-IV:
autosomal- Ecchymoses,
recessive. arterial rupture.
 Type-VII: Defect Dangerous due
in collagen type I to rupture
aneurysms.
  Type-IX: X-linked  Type-VI:
recessive Retinal
detachment,
corneal rupture

Osteogenesis Connective Defects in Collagen Type Multiple fractures after

Imperfecta tissue disease I 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,

(Glycogen Storage Disease Storage Debranching enzyme hepatomegaly,
Type III)
Disease deficiency (can only break hypoglycemia.
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
(Glycogen Storage Disease Storage muscle phosphorylase weakness, easy
Type V)
Disease deficiency (cannot utilize fatigability.
glycogen in skeletal Myoglobinuria with
muscle) ------> strenuous exercise.
accumulation of glycogen
in skeletal muscle.
Pompe's Disease Glycogen Autosomal Recessive. Cardiomegaly,
(Glycogen Storage Disease Storage alpha-1,4-Glucosidase hepatomegaly, and
Type II)
Disease deficiency (cannot break systemic findings,
down glycogen) ------> leading to early death.
accumulate glycogen in
liver, heart, skeletal
muscle.
Von Gierke's Disease Glycogen Autosomal Recessive. Severe fasting
(Glycogen Storage Disease Storage Glucose-6-Phosphatase hypoglycemia,
Type I)
Disease deficiency (cannot break hepatomegaly from lots
down glycogen) ------> of glycogen in liver.
accumulate glycogen in
liver and kidney.
Hemophilia A Hemophilia X-Linked Recessive. Hemorrhage, hematuria,
(Factor VIII Factor VIII deficiency hemarthroses.
Deficiency) Prolonged PTT.
Hemophilia B Hemophilia X-Linked Recessive. Milder than Hemophilia
(Factor IX Factor IX deficiency. A. Hemorrhage,
Deficiency) hematuria,
hemarthroses.
Prolonged PTT.
Von Willebrand Hemophilia Autosomal dominant and Hemorrhage, similar to
Disease recessive varieties. Von hemophilia.
Willebrand Factor Type-I: Most mild. Type-II:
deficiency ------> defect in Intermediate. Type-III: most
initial formation of platelet
severe, with recessive
plugs, and shorter half-life
inheritance (complete absence).
of Factor VIII in blood.
Ataxia- Immune Autosomal Recessive. Cerebellar ataxia,
Telangiectasia deficiency Unknown. Numerous telangiectasia (enlarged
Combined chromosomal breaks and capillaries of face and
Deficiency
elevated AFP is found. skin), B and T-Cell
Symptomatic by age 2 deficiencies, IgA
years. deficiency.
Chédiak-Higashi Immune Defect in polymerization Recurrent pyogenic
Syndrome deficiency of microtubules in infections,
Phagocyte neutrophils ------> failure Staphylococcus,
Deficiency
in neutrophil migration Streptococcus.
and phagocytosis. Also
results in failure in
lysosomal function in
neutrophils.
Chronic Immune X-Linked (usually) Failure of phagocytes
Granulomatous deficiency NADPH Oxidase leads to susceptibility to
Disease Phagocyte deficiency ------> no infections, especially
Deficiency
formation of peroxides Staph Aureus and
and superoxides ------> no Aspergillus spp. B and
oxidative burst in T cells usually remain
phagocytes. normal.
Chronic Immune T-Cell deficiency specific Selective recurrent
Mucocutaneous deficiency to Candida. Candida infections.
Candidiasis T-Cell Deficiency Treat with anti-fungal
drugs.
Job's Syndrome Immune A failure to produce High histamine levels,
deficiency gamma-Interferon by T- eosinophilia. Recurrent
Phagocyte Helper cells, leading to an cold (non-
Deficiency
increase in TH2 cells (no inflammatory)
negative feedback) ------> Staphylococcal
excessively high levels of abscesses (resulting
IgE. from high histamine),
eczema.
Selective IgA Immune IgA deficiency may be The most common
Deficiency deficiency due to a failure of heavy- congenital immune
B-Cell Deficiency chain gene switching. deficiency.  There also
exists selective IgM and
IgG deficiencies, but
they are less common.
Severe Combined Immune Autosomal Recessive. Severe deficiency in
Immunodeficiency deficiency Adenosine Deaminase both humoral and
(SCID) Combined deficiency ------> cellular immunity, due
Deficiency
accumulation of dATP to impaired DNA
------> inhibit synthesis. Bone marrow
ribonucleotide reductase transplant may be
------> decrease in DNA helpful in treatment.
precursors
Thymic Aplasia Immune Failure of development of T-Cell deficiency from
(DiGeorge deficiency the 3rd and 4th no thymus.
Syndrome) T-Cell Deficiency Pharyngeal Pouches Hypocalcemic tetany
------> agenesis of the from primary
thymus and parathyroid parathyroid deficiency.
glands.
Wiskott-Aldrich Immune Inability to mount initial In infancy, recurrent
Syndrome deficiency IgM response to the pyogenic infections,
Combined capsular polysaccharides eczema,
Deficiency
of pyogenic bacteria. thrombocytopenia,
excessive bleeding. IgG
levels remain normal.
X-Linked Immune X-Linked. Mutation in Recurrent pyogenic
Agammaglobulinemi deficiency gene coding for tyrosine infections after 6
a (Bruton's Disease) B-Cell Deficiency kinase causes failure of months (when maternal
Pre-B cells to differentiate antibodies wear off).
into B-Cells. Can treat with
polyspecific gamma
globulin preparations.
Fabry's Disease Lysosomal X-Linked Recessive. Angiokeratomas (skin
Storage alpha-Galactosidase A lesions) over lower
Disease deficiency ------> buildup trunk, fever, severe
of ceramide trihexoside burning pain in
in body tissues. extremities,
cardiovascular and
cerebrovascular
involvement.
Gaucher's Disease Lysosomal Autosomal Recessive.  Type-I: Adult
Storage Glucocerebrosidase form. 80% of
Disease deficiency ------> cases, retain
accumulation of partial activity.
 glucocerebrosides Hepatosplenome
(gangliosides, galy, erosion of
sphingolipids) in femoral head,
lysosomes throughout the mild anemia.
body. 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
Storage iduronosulfate sulfatase severe than Hurler
Disease deficiency ------> buildup Syndrome.
of mucopolysaccharides Hepatosplenomegaly,
(heparan sulfate and micrognathia, retinal
dermatan sulfate) degeneration, joint
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
mucopolysaccharides 10. 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,
accumulation of GM2 blindness (amaurosis).
ganglioside in neurons. Death before age 4.
Albinism Nitrogen Autosomal Recessive. Depigmentation, pink
Metabolism Tyrosinase deficiency eyes, increased risk of
Defect ------> inability to skin cancer.
synthesize 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 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, blond hair, genu
or lost affinity for valgum, failure to
pyridoxine, Vit. B6) ------> thrive, thromboembolic
buildup of homocystine episodes, fatty changes
and deficiency of cysteine. of liver.
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 Phosphoribosyltransfera mutilation (autistic
se (HGPRT) deficiency behavior),
------> no salvage pathway choreoathetosis,
for purine re-synthesis spasticity.
------> buildup of purine
metabolites
Maple Syrup Urine Nitrogen Autosomal Recessive. Severe CNS defects,
Disease Metabolism Deficiency of branched mental retardation,
Defect chain keto-acid death. Person smells
 decarboxylase ------> no like maple syrup or
degradation of branched- burnt sugar. Treatment:
chain amino acids ------> remove the amino acids
buildup of isoleucine, from diet.
valine, leucine.
Phenylketonuria Nitrogen Autosomal Recessive. Symptoms result from
(PKU) Metabolism Phenylalanine accumulation of
Defect hydroxylase deficiency phenylalanine itself.
(cannot break down Phe Mental deterioration,
nor make Tyr) ------> hypopigmentation
buildup of phenylalanine, (blond hair and blue
phenyl ketones eyes), mousy body odor
(phenylacetate, phenyl (from phenylacetic acid
lactate, phenylpyruvate) in in urine and sweat).
body tissues and CNS. Treatment: remove

phenylalanine from diet.

Glucose-6-Phosphate RBC Disease X-Linked Recessive. Susceptibility to

Dehydrogenase Glucose-6-Phosphate oxidative damage to
(G6PD) Deficiency Dehydrogenase (G6PD) RBC's, leading to
deficiency ------> no hemolytic anemia. Can
hexose monophosphate be elicited by drugs
shunt ------> deficiency in (primaquine,
NADPH ------> inability sulfonamides, aspirin),
to maintain glutathione in fava beans (favism).
reduced form, in RBC's More prevalent in
blacks.
Glycolytic enzyme RBC Disease Autosomal Recessive. Hemolytic anemia
deficiencies Defect in hexokinase, results from any defect
glucose-phosphate in the glycolysis
isomerase, aldolase, pathway, as RBC's
triose-phosphate depend on glycolysis
isomerase, phosphate- for energy.
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,
primary hyper- hypokalemic alkalosis.
reninemia. No hypertension.
Fanconi's Syndrome Renal Autosomal Recessive. (1) Cystine deposition
Type I Deficient resorption in throughout body,
(Child-onset cystinosis) proximal tubules. cystinuria. (2) Defective
tubular resorption leads
to 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
(Adult-onset) proximal tubules. without the cystinosis.
Adult onset
osteomalacia, amino-
aciduria, polyuria,
glycosuria.
Autosomal Renal Autosomal Dominant. Numerous, disparate,
Dominant Polycystic Autosomal heterogenous renal
Kidney Disease Dominant
cysts occurring
(ADPKD) bilaterally. Onset in
Disorders
adult life. Associated
with liver cysts.

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