Which clinical feature best distinguishes phenylketonuria (PKU) from alkaptonuria?

Explanation

## Distinguishing PKU from Alkaptonuria ### Key Biochemical Defects | Feature | PKU | Alkaptonuria | |---------|-----|---------------| | **Enzyme defect** | Phenylalanine hydroxylase ↓ | Homogentisate oxidase ↓ | | **Accumulating metabolite** | Phenylalanine, phenylacetate | Homogentisic acid | | **Urine colour** | Normal initially | Dark/black on standing | | **Onset of symptoms** | Neonatal (if untreated) | Adulthood (3rd–4th decade) | | **CNS involvement** | Yes (severe if untreated) | No | | **Arthritis/Ochronosis** | No | Yes (pathognomonic) | ### Clinical Presentation Timeline **PKU (Untreated):** 1. Neonatal period: musty/mousy odour in urine and sweat 2. Weeks to months: failure to thrive, developmental delay 3. Infancy–childhood: intellectual disability, light skin, eczema, seizures 4. No arthritis or darkening of connective tissue **Alkaptonuria:** 1. Childhood–adolescence: dark urine (homogentisic acid oxidizes to dark polymer) 2. Adulthood (30s–40s): ochronosis (blue-black pigmentation of cartilage, sclera, skin) 3. Later adulthood: degenerative arthritis (spine, large joints) 4. **No intellectual disability or developmental delay** ### Why This Distinction Matters **Key Point:** PKU causes severe **neurological damage in infancy** if untreated, while alkaptonuria is **asymptomatic in childhood** and manifests as **pigmentation and arthritis in adulthood**. This temporal and phenotypic separation is the cardinal discriminator. **High-Yield:** Intellectual disability + light skin + neonatal presentation = PKU. Dark urine + ochronosis + normal cognition = alkaptonuria. **Clinical Pearl:** Newborn screening for PKU (elevated plasma phenylalanine >20 mg/dL) prevents intellectual disability entirely. Alkaptonuria is often diagnosed incidentally when a patient presents with arthritis or darkening of ear cartilage. [cite:Robbins 10e Ch 5] [cite:KD Tripathi 8e Ch 35]