Clinical Scenario: Fair skin | Eczema | musty body order
A 5-week-old infant who was normal at birth is brought with poor feeding, irritability, and failure to achieve expected developmental milestones. On examination, the infant has eczema, fair skin and hair compared with the parents, and a musty body odor. Laboratory investigations reveal markedly elevated plasma phenylalanine with low tyrosine levels. Which of the following is the most appropriate long-term management?
A. Dietary phenylalanine restriction with tyrosine supplementation
B. High-protein diet with folic acid supplementation
C. Levodopa and carbidopa therapy
D. Oral tetrahydrobiopterin for all patients
E. Vitamin B12 supplementation
Correct answer & Explanation:
Correct Answer:
A. Dietary phenylalanine restriction with tyrosine supplementation
Explanation
Phenylketonuria (PKU) is an autosomal recessive disorder caused most commonly by phenylalanine hydroxylase (PAH) deficiency, leading to impaired conversion of phenylalanine to tyrosine.
Untreated infants are normal at birth but later develop:
- Developmental delay and intellectual disability
- Seizures
- Eczema
- Musty (mousy) body odor
- Fair skin and light hair due to reduced melanin synthesis
- Behavioral problems
The cornerstone of treatment is:
- Lifelong dietary restriction of phenylalanine
- Tyrosine supplementation, as tyrosine becomes an essential amino acid
Early treatment, ideally following newborn screening, prevents irreversible neurological damage.
Why the other options are incorrect
- B. High-protein diet with folic acid supplementation – Increases phenylalanine intake and worsens the condition.
- C. Levodopa and carbidopa therapy – Used for Parkinson disease, not PKU.
- D. Oral tetrahydrobiopterin for all patients – Sapropterin (BH4) benefits only selected BH4-responsive PKU patients and is not appropriate for all cases.
- E. Vitamin B12 supplementation – Has no role in treating PKU.
High-Yield MRCPCH Pearl
A newborn with developmental delay, eczema, musty odor, and hypopigmentation should immediately raise suspicion for PKU. The diagnosis is confirmed by elevated plasma phenylalanine on newborn screening or quantitative amino acid analysis. Early dietary treatment prevents severe neurodevelopmental impairment.
References:
- Nelson Textbook of Pediatrics, 22nd Edition
- GeneReviews®: Phenylalanine Hydroxylase Deficiency
- American College of Medical Genetics and Genomics (ACMG) Guidelines for Phenylketonuria Management
