Genetics

Question 1

Urine odor: sweaty feet, acrid

Answer 1

Glutaric acidemia type III, isovaleric acidemia

Question 2

Urine odor: swimming pool

Answer 2

Hawkinsinuria

Question 3

Urine odor: cat urine

Answer 3

3-hydroxy-3-methylglutaric aciduria

Question 4

Urine odor: Boiled cabbage

Answer 4

Hypermethioninemia

Question 5

Urine odor: tomcat urine

Answer 5

multiple carboxylase deficiency

Question 6

Urine odor: Hops-like

Answer 6

Oasthouse urine diseaes

Question 7

Urine odor: mousy or musty

Answer 7

Phenylketonuria

Question 8

Urine odor: rotting fish

Answer 8

Trimethylaminuria

Question 9

Urine odor: boiled cabbage, rancid butter

Answer 9

Tyrosinemia

Question 10

Classic phenylketonuria
enzyme deficiency __
phenylalanine level __

Answer 10

Classic PKU
enzyme deficiency: phenylalanine hydroxylase
phenylalanine level: >20 mg/dL

Question 11

Deficiency of fumarylacetoacetate hydrolase
Elevated succinylacetone
Presents between 2 and 6 mo
Acute hepatic crisis heralds onset
Acute peripheral neuropathy: severe pain in the legs, extensor hypertonia of the neck and trunk, vomiting, paralytic ileus, self-induced injuries, lasting 1-7 days
Fanconi-like syndrome
Treatment of choice is nitisinone

Answer 11

Tyrosinemia Type I (Tyrosinosis, Hereditary Tyrosinemia, Hepatorenal Tyrosinemia)

Question 12

Deficiency of tyrosine aminotransferase
Hypertyrosinemia (20-50 mg/dL)
Palmar and plantar hyperkeratosis, herpetiform corneal ulcers, intellectual disability, ocular manifestations (tearing, redness, pain, photophobia), skin lesions (painful hyperkeratotic plaques)

Answer 12

Tyrosinemia Type II (Richner-Hanhart syndrome, Oculocutaneous Tyrosinemia)

Question 13

Developmental delay, seizures, intermittent ataxia, self-destructive behavior.
No liver or renal abnormalities
4-hydroxyphenulpyruvic acid and metabolites in the urine

Answer 13

Tyrosinemia Type III (Primary deficiency of 4-HPPD)

Question 14

Deficiency of homogentisic acid oxidase
Ochronosis (dark spots on the sclera or ear cartilage), arthritis, blackening of urine on standing
Treatment: nitisinone, phenylalanine- and tyrosine-restricted diet

Answer 14

Alkaptonuria

Question 15

Lipidosis
B galactosidase deficiency
hepatosplenomegaly, angiokeratoma, developmental delay, macular cherry-red spot
Facies: low-set ears, frontal bossing, depressed nasal bridge, long philtrum
Death usually occur by 3-4 yr

Answer 15

GM1 Gangliosidosis

Question 16

B-hexosaminidase deficiency
loss of motor skills, mental deteriorationincreased startle reaction, macular pallor, retinal cherry-red spots, hyperacusis, macrocephaly

Answer 16

GM2 Gangliosidosis

Tay-Sachs disease, Sandhoff disease

Question 17

Acid B-glucosidase deficiency/glucocerebrosidase
hematologic abnormalities, organomegaly, skeletal involvement, bone pain,
Pathologic hallmark: wrinkled paper appearance
ERT

Answer 17

Gaucher

Question 18

Acid sphingomyelinase deficiency

Hepatosplenomegaly, psychomotor retardation, neurodevelopmental regression,

Answer 18

Niemann-Pick

Question 19

a-galactosidase deficiency
angiokeratoma ("bathing trunk areas"), hypohidrosis, corneal and lenticular opacities, acroparesthesias, vascular disease of the kidney, heart, brain
Pain is the most debilitating symptom
"Maltese crosses" in urinary sediment
ERT

Answer 19

Fabry disease

Question 20

Galactocerebrosidase deficiency
Spasticity, cognitive impairment, optic atrophy,
Treatment: umbilical cord blood transplantation

Answer 20

Krabbe disease

Question 21

Ceramidase deficiency

Painful joint swelling and nodule formation

Answer 21

Farber disease

Question 22

Glucose-6-phosphatase deficiency
Growth retardation, hepatomegaly, hypoglycemia, doll-like facies
Biochemical hallmarks: hypoglycema, lactic acidosis, hyperuricemia and hyperlipidemia

Answer 22

GSD Type I: Von Gierke Disease

Question 23

Acid maltase deficiency
Myopathy, cardiomyopathy, respiratory insufficiency
ERT

Answer 23

GSD Type II: Pompe Disease

Question 24

Myophosphorylase defiency

Exercise intolerance, muscle cramps

Answer 24

GSD Type V: McArdle

Question 25

Branching enzyme deficiency | Failure to thrive, hypotonia, hepatomegaly, splenomegaly, cirrhosis

Answer 25

GSD Type IV: Andersen

Question 26

Debrancher enzyme deficiency | Hepatomegaly, growth retardation, muscle weakness, hypoglycemia

Answer 26

GSD Type IIIa: Cori or Forbes

Question 27

Patients with galactosemia are at increased risk for which infection

Answer 27

E. coli neonatal sepsis

Question 28

Iduronate 2-sulfatase deficiency X-linked recessive Clear cornea

Answer 28

Hunter

Question 29

Behavioral problems, sleeping disorder, aggression, progressive dementia, clear cornea

Answer 29

Sanfilippo

Question 30

Hyperuricemia, intellectual disability, dystonic movement disorder, arthric speech, compulsive self-biting

Answer 30

Lesch-Nyhan disease | HPRT deficiency

Question 31

Most common genetic cause of moderate intellectual disability

Answer 31

Trisomy 21

Question 32

Cleft lip often midline; flexed fingers with polydactyly; ocular hypotelorism; holoprosencephaly, hypoplastic or absent ribs Median survival of 7 days; 91% die by 1 year

Answer 32

Trisomy 13 (Patau syndrome)

Question 33

Low birthweight, closed fists with index finger overlapping the 3rd digit and the 5th digit overlapping the 4th, rocker-bottom feet

Answer 33

Trisomy 18 (Edwards syndrome)