# Phenylketonuria

> Phenylketonuria for NEET-PG Paediatrics covers PAH deficiency, musty odour, newborn screening, lifelong low-phenylalanine diet and maternal PKU risks.

- Canonical URL: https://prepelephant.com/topics/neet-pg/paediatrics/phenylketonuria
- Exam / course: NEET-PG · Subject: Paediatrics
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-14
- Last updated: 2026-10-14
- Reference basis: Nelson Textbook of Pediatrics; Ghai Essential Pediatrics
- How to cite: "Phenylketonuria", PrepElephant, https://prepelephant.com/topics/neet-pg/paediatrics/phenylketonuria

## Direct answer

Phenylketonuria is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency of the hepatic enzyme phenylalanine hydroxylase, which converts phenylalanine to tyrosine. Untreated, raised blood phenylalanine damages the developing brain, causing intellectual disability, seizures and a musty odour of the breath, skin and urine. Newborn screening with a heel-prick blood spot, followed by a lifelong low-phenylalanine diet started early, prevents most of this damage.

## What you must remember

- **Inheritance and defect:** autosomal recessive, usually from phenylalanine hydroxylase (PAH) gene mutations on chromosome 12; tetrahydrobiopterin (BH4) cofactor defects are the main alternative cause of raised phenylalanine.
- **Classic odour:** a musty or mousy smell from phenylketones, such as phenylacetate, in sweat, urine and breath.
- **Screening:** a heel-prick blood spot taken after several days of protein feeding, with raised results repeated and confirmed by plasma amino acid analysis.
- **Diet principle:** natural protein is restricted, with phenylalanine-free amino acid formula supplying the balance of protein.
- **Tyrosine:** supplemented because it stops being made from phenylalanine and becomes essential in this disorder.
- **Aspartame:** a dietary source of phenylalanine, so diet drinks and sugar-free products are avoided, and labels in many countries warn of it.
- **Maternal PKU:** raised maternal phenylalanine causes congenital heart disease, microcephaly, growth restriction and intellectual disability in the fetus, whatever the fetal genotype.

## A lifelong pathway from diagnosis to pregnancy

Management is dietary and lifelong, so the steps below follow the child from a positive screen to adult planning. Each step is checked against blood phenylalanine levels, not against symptoms alone.

1. **Confirm the diagnosis:** repeat blood phenylalanine and tyrosine on a plasma amino acid analyser, then run a BH4 loading test to separate BH4 deficiency from PAH deficiency.
2. **Start the diet early:** natural protein is restricted from infancy, and a phenylalanine-free formula supplies the remaining protein needs.
3. **Add tyrosine:** tyrosine is given as a supplement because the body can no longer make enough of it from phenylalanine.
4. **Monitor levels:** blood phenylalanine is checked regularly, with dietary protein adjusted to keep levels in the commonly targeted range of about 120 to 360 micromol/L.
5. **Consider BH4 therapy:** responsive patients may take sapropterin, which lowers phenylalanine and can allow more natural protein in the diet.
6. **Plan the pregnancy:** women with PKU start strict control before conception and maintain it through pregnancy, because maternal levels, not the fetal genotype, drive the harm.

## Where the exam tests phenylketonuria

Questions focus on the enzyme, the odour and the maternal effects. Each trap below appears in standard paediatrics MCQs.

- **Trap:** thinking the diet can be relaxed once the child is school-aged. — **Correct:** dietary control is lifelong in classic PKU, with blood phenylalanine kept within the target range.
- **Trap:** attributing a baby's congenital heart disease to the baby's own genotype when the mother has PKU. — **Correct:** maternal hyperphenylalaninaemia is teratogenic, so strict maternal control before conception prevents the harm.
- **Trap:** treating raised phenylalanine with a low-protein diet alone without checking BH4 status. — **Correct:** BH4 deficiency needs a loading test and different treatment, since sapropterin helps only BH4-responsive PAH deficiency.

## Frequently asked questions

### What is the main treatment for phenylketonuria?

Lifelong dietary restriction of phenylalanine is the main treatment for phenylketonuria. It is given with phenylalanine-free amino acid formula and tyrosine supplementation, and it is adjusted using regular blood phenylalanine levels.

### Why is tyrosine supplemented in phenylketonuria?

Tyrosine is supplemented in phenylketonuria because the enzyme that makes it from phenylalanine is deficient. Tyrosine therefore becomes essential in this disorder and must come from the diet.

### Which test screens newborns for phenylketonuria?

Newborn screening measures blood phenylalanine in a heel-prick blood spot taken after several days of protein feeding. Positive results are repeated and confirmed by plasma amino acid analysis, and tandem mass spectrometry is widely used in newborn programmes.

### Why is maternal phenylketonuria dangerous to the fetus?

Maternal hyperphenylalaninaemia crosses the placenta and damages the fetus, causing congenital heart disease, microcephaly, growth restriction and intellectual disability. The fetus can be affected even if it does not have phenylketonuria itself, so maternal control should start before conception.