Learning and behavioural difficulties but not microcephaly in three brothers resulting from undiagnosed maternal phenylketonuria.
Universal screening introduced in the 1960s has reduced the incidence of learning disability resulting from phenylketonuria (PKU), which is a treatable condition. Nonetheless, PKU may still be having an impact on the paediatric-age population. We report a woman with previously undiagnosed PKU who was born before the onset of universal screening. She is of normal intelligence, and so the diagnosis was not suspected until after the birth of her three children. Her serum phenylalanine concentration was found to be in excess of 1 mmol/L, well into the toxic range. She has had three sons, all of whom have a significant degree of learning disability resulting from intrauterine exposure to toxic levels of phenylalanine. None of the sons had microcephaly, a physical sign that, if present, might have helped to point towards the correct diagnosis. We suggest that maternal PKU should be suspected where there is sibling recurrence of cognitive impairment, particularly where the mother was born before the initiation of the neonatal screening programme for PKU.
Department of Clinical Genetics, Addenbrooke's Hospital, Cambridge, UK. charles.shaw-smith@addenbrookes.nhs.uk
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Shaw-Smith
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Hogg
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Reading
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Calvin
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Trump
D000328:Adult; D002648:Child; D002653:Child Behavior Disorders / Q000235:genetics*; D005260:Female; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010641:Phenotype; D010649:Phenylalanine / Q000097:blood; D017042:Phenylketonuria, Maternal / Q000097:blood / Q000235:genetics*; D011247:Pregnancy
D010649:Phenylalanine