Genetic Diseases

Question 1

Chromosome 4 (associated diseases)

Answer 1

ADPKD (PKD2 mutation), Huntington disease

Question 2

Chromosome 5 (associated diseases)

Answer 2

Cri-du-chat syndrome, familial adenomatous polyposis (APC)

Question 3

Chromosome 7 (associated diseases)

Answer 3

Williams syndrome, cystic fibrosis

Question 4

Chromosome 9 (associated diseases)

Answer 4

Friedreich ataxia

Question 5

Chromosome 11 (associated diseases)

Answer 5

Wilms tumor

Question 6

Chromosome 13 (associated diseases)

Answer 6

Patau syndrome (trisomy), Wilson disease

Question 7

Chromosome 15 (associated diseases)

Answer 7

Prader-Willi syndrome (maternal imprinting), Angelman syndrome (paternal imprinting), Marfan syndrome

Question 8

Chromosome 16 (associated diseases)

Answer 8

ADPKD (PKD1 mutation)

Question 9

Chromosome 17 (associated diseases)

Answer 9

Neurofibromatosis type 1

Question 10

Chromosome 18 (associated diseases)

Answer 10

Edwards syndrome

Question 11

Chromosome 21 (associated diseases)

Answer 11

Down syndrome

Question 12

Chromosome 14 (associated diseases)

Answer 12

Familial early-onset Alzheimer’s disease (PSEN1)

Question 13

Chromosome 22 (associated diseases)

Answer 13

Neurofibromatosis type 2, DiGeorge syndrome

Question 14

X chromosome (associated diseases)

Answer 14

Fragile X syndrome, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry disease, G6PD deficiency, ocular albinism, Lesch-Nyhan syndrome, Hunter syndrome, ornithine transcarbamylase deficiency

Question 15

Chromosome 3 (associated diseases)

Answer 15

von Hippel-Lindau disease, renal cell carcinoma

Question 16

Von Gierke disease (glycogen storage disease type I)

Answer 16

Autosomal recessive; glucose-6-phosphatase deficiency; severe fasting hypoglycemia, glycogen accumulation in liver, high blood lactate, high triglycerides, high uric acid, hepatomegaly; tx with frequent oral glucose/cornstarch, avoid fructose and galactose

Question 17

Pompe disease (glycogen storage disease type II)

Answer 17

Autosomal recessive; lysosomal a-1,4-glucosidase (acid maltase) deficiency; cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, early death

Question 18

Cori disease (glycogen storage disease type III)

Answer 18

Autosomal recessive; debranching enzyme (a-1,6-glucosidase) deficiency; milder form of Von Gierke disease (fasting hypoglycemia, glycogen accumulation in liver, high triglycerides, high uric acid, hepatomegaly) with normal lactate; tx with oral glucose/cornstarch

Question 19

McArdle disease (glycogen storage disease type V)

Answer 19

Autosomal recessive; skeletal muscle glycogen phosphorylase deficiency; glycogen accumulation in muscle, painful muscle cramping, myoglobinuria (red urine) with strenuous exercise, arrhythmia; tx with vitamin B6

Question 20

Fabry disease

Answer 20

X-linked recessive; a-galactosidase A deficiency, leading to ceramide trihexoside accumulation; peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease

Question 21

Gaucher disease

Answer 21

Autosomal recessive; most common lysosomal storage disease; glucocerebrosidase (b-glucosidase) deficiency, leading to glucocerebroside accumulation; hepatosplenomegaly, pancytopenia, osteoporosis, aseptic necrosis of femur, bone crisis, Gaucher cells (lipid-laden macrophages resembling crumpled tissue paper); tx with recombinant glucocerebrosidase

Question 22

Niemann-Pick disease

Answer 22

Autosomal recessive; sphingomyelinase deficiency, leading to accumulation of sphingomyelin; progressive neurodegeneration, hepatosplenomegaly, foam cells, cherry-red spot on macula

Question 23

Tay-Sachs disease

Answer 23

Autosomal recessive; hexosaminidase A deficiency, leading to accumulation of GM2 ganglioside; progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin; no hepatosplenomegaly

Question 24

Krabbe disease

Answer 24

Autosomal recessive; galactocerebrosidase deficiency, leading to accumulation of galactocerebroside and psychosine; peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Question 25

Metachromatic leukodystrophy

Answer 25

Autosomal recessive; arylsulfatase A deficiency, leading to accumulation of cerebroside sulfate; central and peripheral demyelination with ataxia and dementia

Question 26

Hurler syndrome

Answer 26

Autosomal recessive; a-L-iduronidase deficiency, leading to accumulation of heparan sulfate and dermatan sulfate; developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly

Question 27

Hunter syndrome

Answer 27

X-linked recessive; iduronate sulfatase deficiency, leading to accumulation of heparan sulfate and dermatan sulfate; mild Hurler symptoms (developmental delay, gargoylism, airway obstruction, hepatosplenomegaly) with aggressive behavior and no corneal clouding

Question 28

idopathic pulmonary arterial hypertension

Answer 28

due to inactivating mutation in BMPR2, which normally inhibits vascular smooth muscle proliferation; causes pulmonary hypertension (mean pulmonary artery pressure > 25 mmHg) with normal PCWP (

Question 29

pyruvate dehydrogenase complex deficiency

Answer 29

X-linked recessive; high serum lactate and alanine; presents in infancy, causes neurologic deficits, lactic acidosis; tx = ketogenic diet (high-fat, lysine, and leucine)

Question 30

essential fructosuria

Answer 30

autosomal recessive; defect in fuctokinase, leading to increased fructose in urine; usually asymptomatic

Question 31

fructose intolerance

Answer 31

autosomal recessive; deficiency of aldolase B, leading to increased fructose-1-phosphate and decreased phosphate stores, which suppresses glycogenolysis and gluconeogenesis; causes hypoglycemia, jaundice, cirrhosis, vomiting after consumption of fructose-containing foods (juice, honey, fruit); urine dipstick is negative; tx = avoidance of dietary sucrose and fructose

Question 32

galactokinase deficiency

Answer 32

autosomal recessive; deficiency of galactokinase, leads to increased galacitol and galactose in blood and urine; presents as infantile cataract/failure to track

Question 33

classic galactosemia

Answer 33

autosomal recessive; absent galactose-1-phosphate-uridyltransferase, leads to increased serum galacitol; causes failure to thrive, jaundice, hepatomegaly, infantile cataract, intellectual disability, E. coli sepsis; tx = avoidance of dietary galactose and lactose

Question 34

hyperammonemia

Answer 34

increased serum ammonium, which leads to depleted a-ketoglutarate and suppression of the TCA cycle; tx = decreased protein intake, lactulose (acidifies GI tract/traps NH4+), rifaximin (decreases colonic ammoniagenic bacteria), benzoate or phenylbutyrate (both bind amino acid and lead to excretion)

Question 35

N-acetylglutamate synthase deficiency

Answer 35

leads to decreased carbamoyl phosphate synthetase I activity (uses N-acetylglutamate as a cofactor), which results in hyperammonemia; presents in neonates as poor regulation of respiration and temperature, poor feeding, developmental delay, and intellectual disability

Question 36

ornithine transcarbamylase deficiency

Answer 36

X-linked recessive; leads to increased orotic acid, decreased BUN, and hyperammonemia; presents in infancy

Question 37

phenylketonuria

Answer 37

autosomal recessive; due to decreased phenylalanine hydroxylase OR decreased BH4, leads to increased phenylalanine and increased phenylketones in urine; causes intellectual disability, seizures, musty body odor, fair skin, eczema; tx = dietary modification (low Phe, high Tyr and BH4)

Question 38

maternal PKU

Answer 38

caused by pregnant mother with PKU who does not follow proper diet during pregnancy; infant may present with microcephaly, intellectual disability, growth retardation, congenital heart defects

Question 39

maple syrup urine disease

Answer 39

autosomal recessive; deficient a-ketoacid dehydrogenase (uses B1 as a cofactor), leading to increased serum ketoacids; causes intellectual disability, CNS defects, death; tx = avoid dietary leucine, isoleucine, and valine, supplement B1

Question 40

alkaptonuria

Answer 40

autosomal recessive; deficient homogenstisate oxidase, leading to accumulation of pigment-forming homogentisic acid; causes dark pigmented skin and connective tissue, arthralgia, brown sclerae, and urine that turns black on prolonged exposure to air

Question 41

homocystinuria

Answer 41

autosomal recessive; due to deficient cystathionine synthase, decreased affinity of cystathionine synthase for vitamin B6, or deficient homocysteine methyltransferase; all forms lead to excess homocysteine in urine and cause intellectual disability, osteoporosis, marfanoid habits, kyphosis, lens subluxation, thrombosis and atherosclerosis; tx = decreased dietary methionine (for first type), increased dietary cysteine (for first and second types), B12 supplementation (for first type), B6 supplementation (for second type), increased dietary methionine (for third type)

Question 42

cystinuria

Answer 42

autosomal recessive; defect in renal PCT transporter, leads to impaired reabsorption of cysteine, ornithine, lysine, and arginine (COLA); causes recurrent hexagonal cystine kidney stones; tx = alkalization of urine, penicillamine