Metabolic Disorder Defective Molecule

Question 1

I-Cell Disease

Answer 1

N-acetylglucosaminyl-1-phosphotransferase

failure of Golgi to phosphorylate mannose residues

Question 2

G6PD Deficiency

Answer 2

Glucose-6-Phosphate Dehydrogenase

(necessary for HMP shunt and reduction of Glutathione, which is important for detoxifying free radicals and peroxides–> leads to hemolytic anemia)

Question 3

Essential Fructosuria

Answer 3

Fructokinase

Question 4

Fructose Intolerance

Answer 4

Aldolase B

–> leads to accumulation of Fructose-1-Phosphate (hypoglycemia, jaundice, cirrhosis, vomiting)

Question 5

Galactokinase Deficiency

Answer 5

Galactokinase

—> leads to accumulation of Galactitol

Question 6

Classic Galactosemia

Answer 6

Galactose-1-phosphate-uridyltransferase

—> toxin buildup leads to failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability, e. coli sepsis in neonates

Question 7

PDC Deficiency

Answer 7

Pyruvate Dehydrogenase Complex

—> causes buildup of pyruvate, shunted to lactate (via LDH) and alanine (via ALT)- neurologic defects, lactic acidosis, high serum alanine

Question 8

Lactose Intolerance

Answer 8

Lactase

Bloating, cramps, flatulence, osmotic diarrhea

Question 9

Congenital Hyperammonemia

Answer 9

N-acetylglutamate synthase

Required co-factor for carbamoyl phosphate synthetase I

Question 10

OTC Deficiency

Answer 10

Ornithine Transcarbamylase

most common urea cycle disorder, leads to increased blood and urine orotic acid, DECREASED BUN

Question 11

Phenylketonuria

Answer 11

Phenylalanine Hydroxylase (enzyme) OR Tetrahydrobiopterin (cofactor for conversion to tyrosine)

intellectual disability, growth retardation, seizures, fair skin, eczema, “musty” body odor

Question 12

Maple Syrup Urine Disease

Answer 12

a-ketoacid dehydrogenase

blocked degradation of isoleucine, leucine, and valine
severe CNS defects, intellectual disability, and death.

Question 13

Alkaptonuria

Answer 13

Homogentisate oxidase

Buildup of homogentisic acid–> Dark connective tissue, brown pigmented sclerae, black urine upon prolonged air exposure, arthralgias

Question 14

Homocystinuria

Answer 14

Cystathione synthase

Excess homocysteine buildup–> homocysteine in urine, intellectual disability, osteoporosis, marfanoid habitus, kyphosis, lens subluxation (downward and inward), thrombosis, atherosclerosis

Question 15

Cystinuria

Answer 15

Defective Reabsorption in PCT of Cysteine, Ornithine, Lysine, and Arginine (COLA)

Question 16

Von Gierke Disease (type I GSD)

Answer 16

Glucose-6-Phosphate

Severe fasting hypoglycemia, glycogen buildup, increased lactate, increased triglycerides, increased uric acid, hepatomegaly

Question 17

Pompe Disease (type II GSD)

Answer 17

Lysosomal a-1,4,-glucosidase (acid maltase)

Cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, death

Question 18

Cori Disease (type III GSD)

Answer 18

a-1,6-glucosidase (debranching enzyme)

symptomatically presents as milder form of Von Gierke- hypoglycemia, glycogen buildup, increased lactate, increased triglycerides, increased uric acid, hepatomegaly

Question 19

McArdle Disease (type V GSD)

Answer 19

Glycogen Phosphorylase (myophosphorylase)–> skeletal muscle

increased muscle glycogen, painful muscle cramps, myoglobinuria with strenuous exercise, arrhythmia (due to electrolyte abnormalities)

Question 20

Fabry Disease

Answer 20

a-galactoside A

Buildup of Ceramide trihexoside

X-linked recessive (only this and Hunter are XLR- all other board relevant LSDs are AR) Peripheral neuropathy, angiokeratomas, CV/Renal disease

Question 21

Gaucher Disease

Answer 21

Glucocerebrosidase (B-glucosidase)

Buildup of Glucocerebroside

Most common LSD- hepatosplenomegaly, pancytopenia, aseptic necrosis of femur, bone crises, lipid-laden macrophages

Question 22

Niemann-Pick Disease

Answer 22

Sphingomyelinase

Buildup of Sphingomyelin

Progressive neurodegeneration, hepatosplenomegaly, foam cells, “cherry-red” spot on macula

Question 23

Tay-Sachs Disease

Answer 23

Hexosaminidase A

Buildup of GM2 ganglioside

Progressive neurodegeneration, developmental delay, “cherry-red” spot on macula, lysosomes with onion skin, NO HEPATOSPLENOMEGALY, UNLIKE NIEMANN-PICK

Question 24

Krabbe Disease

Answer 24

Galactocerebrosidase

Buildup of Galactocerebroside and psychosine

Peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Question 25

Metachromatic leukodystrophy

Answer 25

Arylsulfatase A

Buildup of Cerebroside sulfate

Central and peripheral demyelination with ataxia and dementia.

Question 26

Hurler Syndrome

Answer 26

a-L-iduronidase

Buildup of heparan sulfate and dermatan sulfate

Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly AUTOSOMAL RECESSIVE (Hunter-very similar disease is XLR)

Question 27

Hunter Syndrome

Answer 27

Iduronate Sulfatase

Buildup of heparan sulfate and dermatan sulfate

Developmental delay, gargoylism, airway obstruction, hepatosplenomegaly, aggressive behavior NO CORNEAL CLOUDING—> HUNTERS NEED TO SEE THEIR PREY

UNLIKE HURLER-> XLR UNLIKE MOST OTHER LSDS, WITH EXCEPTION OF FABRY

Question 28

Systemic Primary Carnitine Deficiency

Answer 28

Defective Long Chain Fatty Acid transport

—>leads to toxic accumulation of long chain fatty acids–> weakness, hypotonia, hypoketotic hypoglycemia

Question 29

Medium chain acyl-CoA dehydrogenase deficiency

Answer 29

Medium chain acyl-CoA dehydrogenase- Defective fatty acid oxidation

accumlation of 8-10 carbon fatty acyl carnitines in blood and hypoketotic hypoglycemia
can present with vomiting, lethargy, seizures, coma, and liver dysfunction

Question 30

Type I Dyslipidemia

Answer 30

Lipoprotein lipase deficiency OR altered Apo C-II

Hyperchylomicronemia

causes pancreatitis, hepatosplenomegaly, eruptive/pruritic xanthomas, creamy layer of blood

Question 31

Type IIa Dyslipidemia

Answer 31

Absent or defective LDL receptors

familial hypercholesterolemia

accelerated athersclerosis (possible MI before age 20), Achilles xanthomas, corneal arcus

Question 32

Type IV Dyslipidemia

Answer 32

Hepatic overproduction of VLDL

Hypertriglyceridemia

can cause acute pancreatitis