Biochemistry · Amino Acid Metabolism and Urea Cycle (Disorders, Phenylketonuria)

A newborn screened positive for elevated phenylalanine has maternal PKU. The mother has PKU but the newborn's PAH gene is normal. What condition affects the newborn?

  • A Classical PKU in the newborn due to hereditary transmission
  • B Transient neonatal hyperphenylalaninemia from immature liver enzymes
  • C Maternal PKU syndrome — fetal exposure to high maternal phenylalanine causes microcephaly, cardiac defects, and intellectual disability despite normal fetal PAH
  • D Biopterin cofactor deficiency in the neonate
Correct answer: C. Maternal PKU syndrome — fetal exposure to high maternal phenylalanine causes microcephaly, cardiac defects, and intellectual disability despite normal fetal PAH

Explanation

Maternal PKU syndrome affects the fetus of an untreated PKU mother. High maternal phenylalanine crosses the placenta; the fetal-to-maternal ratio of phenylalanine is 1.5:1. Even though the fetus/newborn has normal PAH (heterozygous at most), prenatal exposure to phenylalanine levels >600 μmol/L causes teratogenic effects: microcephaly, intellectual disability, intrauterine growth restriction, and congenital heart defects (particularly conotruncal). The newborn's phenylalanine is elevated at birth but normalizes once breast/formula feeding begins and the mother's phenylalanine source is removed.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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