"PPG LISTS" © QUICK REVISION TABLES
SELECTED GENETIC DISORDERS
Disease Category Pathogenesis / Heredity
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 Normocytic anemia
congenital pancytopenia. with neutropenia.
Hartnup's Disease   Autosomal Recessive.
Defect in GI uptake of
neutral amino acids ------>
malabsorption of
tryptophan (niacin
precursor) ------> niacin
deficiency among other
things.
Kartagener's   Autosomal Recessive.
Syndrome Defect in dynein arms
------> lost motility of cilia infections (due to
Pathology, Cardinal
Symptoms
Meconium ileus
(caused by thick,
mucoid meconium),
respiratory
bronchiectasis,
Pseudomonas
pneumonia, pancreatic
insufficiency,
hypertonic (high Cl-
concentration) sweat.
Short stature, microcephaly,
hypogenitalism, strabismus,
anomalies of the thumbs, radii,
and kidneys, mental retardation,
and microphthalmia.
Pellagra-like syndrome
(diarrhea, dementia,
dermatitis), light-
sensitive skin rash,
temporary cerebellar
ataxia.
Recurrent
sinopulmonary
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
l tandem repeats on the
Sex chromosome long arm of the X-
chromosome. The longer
the number of repeats, the
worse the syndrome.
Tandem repeats tend to
accumulate through
generations.
Klinefelter's Chromosoma Non-disjunction of the sex
Syndrome (XXY) l chromosome during
Sex chromosome Anaphase I of meiosis
------> Trisomy (47,XXY)
Turner's Syndrome Chromosoma Non-disjunction of the sex
(XO) l chromosome during
Sex chromosome Anaphase I of meiosis
------> Monosomy (45,X)
XXX Syndrome Chromosoma Trisomy (47,XXX) and
l other multiple X-
Sex chromosome chromosome
abnormalities.
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-IV:
autosomal
dominant. Defect
in reticular
collagen (type-III)
 Type-VI:
autosomal-
recessive.
 Type-VII: Defect
in collagen type I
Second most common
cause of mental
retardation next to
Down Syndrome.
Macro-orchidism
(enlarged testes) in
males.
Hypogonadism, tall
stature, gynecomastia.
Mild mental retardation.
Usually not diagnosed
until after puberty. One
Barr body seen on
buccal smear.
Streak gonads, primary
amenorrhea, webbed
neck, short stature,
coarctation of Aorta,
infantile genitalia. No
mental retardation. No
Barr bodies visible on
buccal smear.
Usually phenotypically
normal. May see
menstrual abnormalities
or mild mental
retardation in some
cases.
 Type-I:
Diaphragmatic
hernia.
Common,
normal life-
expectancy.
 Type-IV:
Ecchymoses,
arterial rupture.
Dangerous due
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.
Storage Hexosaminidase A
Disease deficiency ------>
accumulation of GM2
ganglioside in neurons.
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.
Metabolism Homogentisic Oxidase
Defect deficiency (inability to
metabolize Phe and Tyr)
------> 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 Phosphoribosyltransfera
se (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
CNS degeneration,
retardation, cherry red-
spot of macula,
blindness (amaurosis).
Death before age 4.
Urine turns dark and
black on standing,
ochronosis (dark
pigmentation of fibrous
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
 decarboxylase ------> no
degradation of branched-
chain amino acids ------>
buildup of isoleucine,
valine, leucine.
Phenylketonuria Nitrogen Autosomal Recessive.
(PKU) Metabolism Phenylalanine
Defect hydroxylase deficiency
(cannot break down Phe
nor make Tyr) ------>
buildup of phenylalanine,
phenyl ketones
(phenylacetate, phenyl
lactate, phenylpyruvate) in
body tissues and CNS.
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.

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

Dehydrogenase
(G6PD) Deficiency
Glycolytic enzyme RBC Disease Autosomal Recessive.
deficiencies
Autosomal Recessive Renal
Polycystic Kidney
Disease (ARPKD)
Bartter's Syndrome Renal
Fanconi's Syndrome Renal
Glucose-6-Phosphate
Dehydrogenase (G6PD)
deficiency ------> no
hexose monophosphate
shunt ------> deficiency in
NADPH ------> inability
to maintain glutathione in
reduced form, in RBC's
Defect in hexokinase,
glucose-phosphate
isomerase, aldolase,
triose-phosphate
isomerase, phosphate-
glycerate kinase, or
enolase. Any enzyme in
glycolysis pathway.
Autosomal Recessive.
Juxtaglomerular Cell
Hyperplasia, leading to
primary hyper-
reninemia.
Autosomal Recessive.
oxidative damage to
RBC's, leading to
hemolytic anemia. Can
be elicited by drugs
(primaquine,
sulfonamides, aspirin),
fava beans (favism).
More prevalent in
blacks.
Hemolytic anemia
results from any defect
in the glycolysis
pathway, as RBC's
depend on glycolysis
for energy.
Numerous, diffuse
bilateral cysts formed in
the collecting ducts.
Associated with hepatic
fibrosis.
Elevated renin and
aldosterone,
hypokalemic alkalosis.
No hypertension.
(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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