A woman with classic phenylketonuria discontinued dietary therapy after adolescence and now plans pregnancy. Her plasma phenylalanine runs at 1500 micromol/L before conception. The greatest fetal risk if she remains off diet during gestation is:

• A Congenital adrenal hyperplasia in the fetus
• B Microcephaly, congenital heart disease, and intellectual disability in the fetus despite the fetus itself being heterozygous ✓
• C Neonatal hypothyroidism detected on screening
• D Galactosemia-like cataracts from galactitol accumulation

Explanation

Maternal PKU describes embryofetopathy caused by high maternal phenylalanine crossing the placenta. Even a heterozygous fetus cannot metabolize the excess, resulting in microcephaly, congenital heart defects, low birth weight, and intellectual disability. Strict preconceptional and prenatal phenylalanine restriction reduces these risks substantially. Congenital adrenal hyperplasia, congenital hypothyroidism, and galactosemia arise from separate metabolic pathways unrelated to maternal phenylalanine levels, so options A, C, and D are distractors.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.