## Diagnosis: Phenylketonuria (PKU) ### Clinical Presentation The vignette describes classic neonatal PKU: poor feeding, lethargy, 'musty' or 'mousy' odour (due to phenylacetate and phenylacetyl-CoA in sweat and urine), fair skin, and light hair (hypopigmentation due to competitive inhibition of tyrosine hydroxylase by excess phenylalanine). ### Investigation of Choice **Key Point:** Serum phenylalanine level by tandem mass spectrometry (MS/MS) is the gold standard confirmatory test for PKU. - **Specificity:** Directly measures the elevated phenylalanine (>20 mg/dL or >1200 µmol/L in PKU) - **Sensitivity:** 100% for classic PKU - **Timing:** Can be performed from day 2–3 of life (after protein feeding begins) - **Quantitative:** Provides exact phenylalanine concentration, allowing severity classification and monitoring of dietary therapy ### Differential Interpretation of Other Tests | Investigation | Role in PKU | Limitation | |---|---|---| | **Tandem MS (phenylalanine)** | Gold standard confirmatory test | — | | **Guthrie test** | Screening tool (neonatal screening program) | Semi-quantitative; not confirmatory | | **Plasma amino acid chromatography** | Can show elevated phenylalanine + low tyrosine | Less specific; slower turnaround | | **Urine organic acids** | Shows phenylpyruvate, phenyllactate, phenylacetate | Indirect evidence; not diagnostic | **High-Yield:** In India, tandem MS is increasingly used in newborn screening programs. The Guthrie test, though still used for population screening, is not confirmatory — it must be followed by MS/MS for definitive diagnosis. ### Clinical Pearl False positives on Guthrie screening (e.g., from transient hyperphenylalaninemia or premature birth) are common; MS/MS confirmation prevents unnecessary treatment of non-PKU infants. **Mnemonic: PKU Diagnosis = PHEN-MS** — **PHEN**ylalanine measured by **MS** (mass spectrometry) is diagnostic.
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.