Phenylketonuria

 

Definition:
A genetic disorder caused by deficiency of the enzyme Phenylalanine Hydroxylase, leading to inability to convert phenylalanine → tyrosine.

Metabolic Defect:
Phenylalanine ↑ → forms phenylpyruvate, phenylacetate, phenyllactate.

Clinical Features:

• Intellectual disability

• Seizures

• Pale skin & blonde hair (↓ melanin)

• Musty or “mousey” odor in urine

• Eczema

• Developmental delay

Diagnosis:

• Guthrie test (newborn screening)

• Elevated phenylalanine levels

Treatment:

• Low-phenylalanine diet

• Special formulas (Lofenalac)

• Avoid aspartame

• Lifelong dietary control

2️⃣ Alkaptonuria

Definition:
A rare genetic disorder due to deficiency of Homogentisate Oxidase, leading to buildup of homogentisic acid.

Metabolic Defect:
Tyrosine & phenylalanine metabolism affected → homogentisic acid accumulates.

Clinical Features:

• Black urine on standing (oxidizes & turns dark)

• Ochronosis (bluish-black pigmentation of cartilage, ear, sclera)

• Early-onset arthritis (spine, knee, hip)

• Joint stiffness

Diagnosis:

• Homogentisic acid in urine

• Urine turns black on exposure to air/alkali

Treatment:

• Vitamin C (slows ochronosis)

• Pain management

• Protein restriction (↓ phenylalanine & tyrosine intake)

• Joint care & physiotherapy

SHORT Differences: PKU vs Alkaptonuria

Feature	PKU	Alkaptonuria
Enzyme Deficiency	Phenylalanine hydroxylase	Homogentisate oxidase
Accumulated Substance	Phenylalanine metabolites	Homogentisic acid
Key Symptom	Mental retardation, musty odor	Black urine, ochronosis
Treatment	Low-Phe diet	Vitamin C, joint care