Review Question - QID 100092

This newborn has screened positive for phenylketonuria (PKU). Treatment consists of restriction of dietary phenylalanine. Since tyrosine is normally produced from metabolism of phenylalanine, tyrosine levels are low, and it is thus an essential amino acid that must be supplemented in the diet of patients with PKU.

If left untreated, PKU may progress to cause mental retardation, microcephaly, and a musty or mousy body odor due to accumulation of phenylalanine, which cannot be metabolized properly. Mothers with this defect should be counseled to follow a strict diet avoiding phenylalanine during pregnancy. Additionally, aspartame (an artificial sweetener which is metabolized in part to phenylalanine) must be avoided.

Waisbren reviews the history and principles behind the newborn screening examination for metabolic disorders. Though the components of the exam vary by state, the first screens were introduced in the 1960s for PKU and have since been expanded to cover many other metabolic disorders.

Koch discusses dietary modifications for PKU and stresses the need for screening to be done at least 12 hours AFTER birth. The newborn screen for PKU is intended to detect serum levels of phenylalanine. The two screening tests are the Guthrie inhibition assay or the McCamon-Robins fluoremetric test. Regarding test characteristics, both are highly accurate, but if a Guthrie test is performed between 12 and 24 hours of life, a confirmatory test must be repeated after 24 hours, while a single McCamon-Robins assay will suffice after 12 hours of life. Implementation of early screening for PKU has drastically reduced mental retardation attributable to PKU.

Illustration A shows the metabolism of phenylalanine to tyrosine. In PKU, the phenylalanine hydroxylase gene has a mutation making the enzyme nonfunctional and resulting in the accumulation of phenylalanine.

Incorrect Answers:
Answer 1: Leucine metabolism is defunct in Maple-Syrup Urine Disease (along with other branched-chain amino acids valine and isoleucine).
Answer 2: Aspartame must be avoided in PKU, since aspartame metabolism can lead to phenylalanine production.
Answer 4: Vitamin B3, niacin, must be supplemented when levels of its precursor, tryptophan, are low. Examples of such conditions include Hartnup disease, isoniazid therapy, and corn-heavy diets.
Answer 5: Inability to breakdown homogentisic acid characterizes alkaptonuria, causing arthritis and urine that darkens in air.