Phenylketonuria (PKU)
Autosomal-recessive phenylalanine hydroxylase deficiency
Overview
Autosomal-recessive deficiency of phenylalanine hydroxylase, so phenylalanine accumulates and is neurotoxic. Detected on the newborn blood-spot screen; untreated it causes intellectual disability, seizures, a 'musty' odour and fair pigmentation. Managed by a lifelong low-phenylalanine diet. Maternal PKU harms the fetus if control is poor in pregnancy.
Recognise
- Detected on NEWBORN blood-spot screening (raised phenylalanine)
- Untreated: developmental delay/intellectual disability, seizures, microcephaly, eczema, 'musty/mousy' body odour, fair hair/skin/blue eyes (reduced melanin)
- Maternal PKU: high maternal phenylalanine is teratogenic (microcephaly, congenital heart disease) — strict control before/in pregnancy
Red flags
- Missed/poorly controlled disease → irreversible neurodevelopmental damage
- Poor maternal control in pregnancy → fetal harm
Differentials & how to tell them apart
Investigations
Newborn blood-spot (heel-prick) screening; confirmatory plasma phenylalanine; genetics.
Management
Lifelong low-phenylalanine diet (sapropterin in responders)
- 1Diagnose on newborn screening; start a strict low-phenylalanine diet early to prevent neurodevelopmental damage. Specialist metabolic dietetics.Gate: Avoid aspartame (a phenylalanine source); women with PKU need STRICT control before and during pregnancy to prevent fetal harm (maternal PKU syndrome)
- 2Lifelong dietary control and monitoring of phenylalanine; sapropterin in responders; pre-pregnancy counselling and tight control.
Key points
Newborn-screen diagnosis; lifelong low-phenylalanine diet prevents intellectual disability. 'Musty' odour + fair, blue-eyed child if missed. Maternal PKU harms the baby — control before pregnancy. (Cross-references the newborn-screening card on child health.)
Monitor & prognosis
Phenylalanine levels; development; pregnancy control.
Normal development if treated early and well.
Source: UK NSC newborn screening; BIMDG