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Flashcards in Congenital Metabolic Disorders Deck (24):

Fructose in the blood and urine

Essential fructosuria: AR defect in fructokinase, benign and asymptomatic


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

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


Galactose in the blood and urine, infantile cataracts

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


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

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


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

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


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

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


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

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.


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

Alkaptonuria (ochronosis): AR deficiency of homogentisate oxidase (converts tyrosine >> fumarate)


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

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


Excess cystine in the urine, precipitation of hexagonal cystine stones

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


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

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


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

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


Cardiomyopathy, systemic findings in liver and muscle, early death

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


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

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


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

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


Neurologic defects, lactic acidosis, increased serum alanine

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)


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

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


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

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


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

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


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

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


Peripheral neuropathy, developmental delay, optic atrophy, globoid cells

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


Central and peripheral demyelination with ataxia, dementia

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


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

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


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

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