A woman with classic untreated phenylketonuria conceives. Her plasma phenylalanine during the first trimester remains above 1200 micromol/L. Which pattern of fetal injury is expected even though the fetus is heterozygous?
- A Microcephaly, congenital heart defects, and intellectual disability despite fetal PAH competence ✓
- B No risk, because the fetus possesses one functional phenylalanine hydroxylase allele
- C Isolated hepatosplenomegaly with cataracts
- D Neonatal hypoglycemia with cardiomyopathy
Correct answer: A. Microcephaly, congenital heart defects, and intellectual disability despite fetal PAH competence
Explanation
Maternal PKU syndrome occurs when an affected mother maintains high phenylalanine in pregnancy. Phenylalanine crosses the placenta freely, so the fetus is exposed regardless of its own genotype, causing microcephaly, intellectual disability, low birth weight, and congenital heart defects. Risk falls sharply when maternal phenylalanine is controlled before conception and kept below roughly 360 micromol/L. Fetal PAH activity cannot compensate because the damage reflects transplacental teratogen exposure.
Reference: Nelson Textbook of Pediatrics, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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