Makindo Medical Notes

🧪 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.