Makindo Medical Notes

Phenylketonuria (PKU)

🧪 Early diagnosis of Phenylketonuria (PKU) and avoidance of phenylalanine can prevent lifelong sequelae.

📖 About

• PKU = a treatable autosomal recessive disease, routinely screened after birth 👶.
• Occurs in ~1 in 10,000–20,000 live births 🌍.
• ⚠️ High phenylalanine → toxic to the brain if untreated.
• 💡 Symptomatic cases are rare in countries with newborn screening + early diet therapy.

🧬 Genetics

• Caused by loss of function in the PAH gene → no phenylalanine hydroxylase.
• ❌ Without PAH, phenylalanine builds up in blood & tissues.

⚙️ Aetiology

• Deficient phenylalanine hydroxylase (chromosome 12).
• Deficiency of cofactor tetrahydrobiopterin (mutations on chromosomes 10 or 4).
• Milder forms exist → Hyperphenylalaninaemia or Non-PKU Hyperphenylalaninaemia.

🩺 Clinical Presentation

• 🧠 Developmental delay, seizures, and microcephaly.
• 🎨 Hypopigmentation (fair hair/skin/eyes due to ↓ melanin).
• 🤯 Hyperactivity, purposeless movements, rocking, athetosis in untreated children.
• 🧴 Musty / mousy body odour (phenylacetic acid).
• 🩹 Mild seborrhoeic or eczematoid rash.
• 🪞 Dysmorphic features: prominent maxilla, wide teeth spacing, enamel hypoplasia.
• 25% → seizures;>50% → abnormal EEG findings.

🔬 Investigations

• 📈 Elevated blood/urine phenylalanine; normal tyrosine & cofactor levels.
• 🍼 Guthrie Test: Heel prick on day 2–3 → detects raised phenylalanine.
• 🧠 EEG: abnormal in ~50%.
• 👶 Prenatal diagnosis: CVS testing.
• MRI/CT: white matter changes in late diagnosis or poor dietary control.

💊 Management

• 🥗 Strict lifelong diet: restrict phenylalanine but allow normal growth.
• 🧪 Cofactor deficiency → low-phenylalanine diet + neurotransmitter precursors.
• 🤰 Maternal PKU: strict control essential to avoid fetal complications.
• 🧠 Even with good control, some cognitive effects may persist.

Cases — Phenylketonuria (PKU)

• Case 1 — Neonatal screening 👶: A 10-day-old baby girl is recalled after a positive Guthrie heel-prick test. She is clinically well but blood phenylalanine is markedly elevated. Diagnosis: PKU detected by newborn screening. Managed with immediate low-phenylalanine diet to prevent neurodevelopmental damage.
• Case 2 — Developmental delay 🧠: A 2-year-old boy presents with delayed milestones, hyperactivity, seizures, and fair hair/skin compared to siblings. History reveals he was born abroad where newborn screening was unavailable. Bloods: very high phenylalanine. Diagnosis: undiagnosed PKU leading to neurocognitive impairment. Managed with strict dietary control and specialist neurodevelopmental follow-up.
• Case 3 — Maternal PKU pregnancy 🤰: A 24-year-old woman with known PKU who discontinued dietary restriction before pregnancy gives birth to a baby with microcephaly, congenital heart defect, and growth restriction. Maternal phenylalanine levels were persistently high during gestation. Diagnosis: maternal PKU syndrome. Managed with pre-conception counselling, strict maternal diet during pregnancy, and neonatal monitoring.

Teaching Point 🩺: PKU is an autosomal recessive deficiency of phenylalanine hydroxylase, leading to toxic accumulation of phenylalanine. - Neonates: detected on screening (heel-prick test, day 5–7 in UK). - Untreated: causes intellectual disability, seizures, microcephaly, fair skin, musty odour. - Management: lifelong low-phenylalanine diet, tyrosine supplementation, and maternal metabolic control before/during pregnancy.