A 9-month-old girl has had two seizures in the past month. She was born at home and received no state-mandated newborn screening. She has developmental delays. Her skin is fair and her hair is a lighter color than that of other family members. Her diapers have a musty odor. Which of the following is most likely to have an increased concentration in this infant’s urine?
Homocysteine
Homogentisic acid
Isoleucine
Isovaleric acid
Phenylacetic acid
Correct answer
Phenylacetic acid
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correct answer: E
The 9-month-old girl likely has phenylketonuria (PKU). In this disorder, there is a deficiency of phenylalanine hydroxylase or tetrahydrobiopterin cofactor, which causes a buildup of phenylalanine. State-mandated newborn screening looks for evidence of PKU to prevent the complications and developmental delays that occur in PKU when phenylalanine builds up in the body. The excess phenylalanine spills over into the urine as phenylacetic acid. The musty odor is a clue to the diagnosis. Since this is a disorder of aromatic amino acid metabolism, there is a musty odor in the diapers. Other common findings in PKU include fair skin, mental retardation, and growth retardation.
There would be an increased concentration of homocysteine in the urine in homocysteinuria, which is caused by cystathionine synthase deficiency, decreased affinity of cystathionine synthase for pyridoxal phosphate, or methionine synthase deficiency. Common findings with this disease include mental retardation, osteoporosis, tall statue, kyphosis, lens subluxation, and atherosclerosis.
Increased isoleucine in the urine likely result from blocked degradation of branched amino acids due to a lack of alpha-ketoacid dehydrogenase deficiency. This disease is maple syrup urine disease and the urine ofen smells like maple syrup.
Homogentisic acid in the urine is seen in alkaptonuria. In this disease, there is a deficiency of homogentisic acid oxidase. The common finding in this disease is that urine turns dark on standing and connective tissue may be darker in color.
Increased concentration of isovaleric acid in the urine can be found in isovaleric acidemia. Patients with isovaleric acidemia may present in early neonatal life with a sudden onset and severe illness. The illness usually begins within a few days of birth with increasing lethargy and decreased feeding, which often causes dehydration and weight loss. The classic odor in this disease is an “odor of sweaty feet” that represents the accumulation in the body of isovaleric acid and related compounds.