Congenital Metabolic Disorders

Question 1

Fructose in the blood and urine

Answer 1

Essential fructosuria: AR defect in fructokinase, benign and asymptomatic

Question 2

Reducing sugar detected in urine following consumption of fruit, juice, or honey; can present with hypoglycemia, jaundice, cirrhosis, vomiting

Answer 2

Fructose intolerance: AR aldolase B deficiency causes accumulation of fructose-1-P > decreased available phosphate > inhibition of glycogenolysis, gluconeogenesis

Question 3

Galactose in the blood and urine, infantile cataracts

Answer 3

Galactokinase deficiency: AR, causes accumulation of galactitol > cataract formation

Question 4

Failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation; can lead to E coli sepsis

Answer 4

Classic galactosemia: AR absence of galactose-1-phosphate uridyltransferase > accumulation of toxic substances including galactitol

Question 5

Ammonia intoxication (tremor, slurred speech, somnolence, vomiting, cerebral edema, blurred vision), elevated ornithine

Answer 5

N-acetylglutamate deficiency: absence of N-acetylglutamate, a required cofactor for carbamoyl phosphate synthetase I > hyperammonemia

Question 6

Ammonia intoxication, orotic acid in blood and urine, decreased BUN

Answer 6

Ornithine transcarbamylase deficiency: X-linked recessive, unable to eliminate ammonia > hyperammonemia; excess carbamoyl phosphate is converted to orotic acid

Question 7

Mental retardation, growth retardation, seizures, fair skin, eczema, musty body odor

Answer 7

Phenylketonuria: AR deficiency of phenylalanine hydroxylase or tetrahydrobiopterin cofactor > build-up or phenylalanine, phenylketones in urine. Requires elimination of phenylalanine from diet and supplementation of tyrosine.

Question 8

Dark connective tissue, brown pigmented sclerae, urine turns black on prolonged exposure to air; may have arthralgias

Answer 8

Alkaptonuria (ochronosis): AR deficiency of homogentisate oxidase (converts tyrosine&raquo_space; fumarate)

Question 9

Elevated homocysteine in the urine, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation, thrombosis, atherosclerosis (COD: stroke and MI)

Answer 9

Homocystinuria: AR and has three types, all resulting in excess homocysteine; cystathionine synthase (CS) deficiency, reduced affinity of CS for pyridoxal phosphate, homocysteine methyltransferase (methionine synthase) deficiency

Question 10

Excess cystine in the urine, precipitation of hexagonal cystine stones

Answer 10

Cystinuria: AR defect of renal PCT and intestinal amino acid transporter for cysteine, ornithine, lysine, and arginine

Question 11

Elevated alpha-ketoacids in the blood, urine smells like burnt sugar, severe CNS defects, mental retardation, death

Answer 11

Maple syrup urine disease: AR deficiency of alpha-ketoacid dehydrogenase > impaired degradation of branched amino acids (isoleucine, leucine, valine)

Question 12

Severe fasting hypoglycemia, increased glycogen in liver, elevated blood lactate, hepatomegaly

Answer 12

GSD type I (Von Gierke disease): glucose-6-phosphatase deficiency

Question 13

Cardiomyopathy, systemic findings in liver and muscle, early death

Answer 13

GSD type II (Pompe disease): deficiency of lysosomal alpha-1,4-glucosidase (acid maltase)

Question 14

Fasting hypoglycemia, increased glycogen in liver, hepatomegaly, normal blood lactate

Answer 14

GSD type III (Cori disease): deficiency of debranching enzyme (alpha-1,6-glucosidase)

Question 15

Increased glycogen in muscle, painful muscle cramps, myoglobinuria with strenuous exercise, arrhythmia

Answer 15

GSD type V (McArdle disease): deficiency of skeletal muscle glycogen phosphorylase (myophosphorylase)

Question 16

Neurologic defects, lactic acidosis, increased serum alanine

Answer 16

Pyruvate dehydrogenase deficiency: causes buildup of pyruvate, which is shunted to lactate and alanine; can be congenital or acquired (ex: B1 deficiency in alcoholics); treat with ketogenic diet (high in fats, lysine and leucine)

Question 17

Peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease

Answer 17

Fabry disease: XR, alpha-galactosidase A deficiency causes buildup of ceramide trihexoside

Question 18

HSM, pancytopenia, aseptic necrosis of femur, bone crises, crinkled paper cells

Answer 18

Gaucher disease: AR, glucocerebrosidase (beta-glucosidase) deficiency causes buildup of glucocerebroside

Question 19

Progressive neurodegeneration, HSM, cherry-red spot on macula, foam cells

Answer 19

Niemann-Pick disease: AR, deficiency of sphingomyelinase causing buildup of sphingomyelin

Question 20

Progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin

Answer 20

Tay-Sachs disease: AR deficiency of hexosaminidase A, causes buildup of GM2 ganglioside

Question 21

Peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Answer 21

Krabbe disease: AR deficiency of galactocerebrosidase causing buildup of galactocerebroside and psychosine

Question 22

Central and peripheral demyelination with ataxia, dementia

Answer 22

Metachromatic leukodystrophy: AR deficiency of arylsulfatase A, causes buildup of cerebroside sulfate

Question 23

Developmental delay, gargoylism, airway obstruction, corneal clouding, HSM

Answer 23

Hurler syndrome (mucopolysaccharidosis): AR deficiency of alpha-L-iduronidase causing buildup of heparan sulfate, dermatan sulfate

Question 24

Mild developmental delay, HSM, and gargoylism, aggressive behavior, no corneal clouding

Answer 24

Hunter syndrome (mucopolysaccharidosis): XR deficiency of iduronate sulfatase, buildup of heparan and dermatan sulfate