Question

A 5 year old child was brought to the physician with a history of black urine. There is no history of fever or any other complaints. There is no growth retardation and all the developmental milestones are normal. The child is suspected to have an enzyme defect for metabolism of an aromatic amino acid. What is the enzyme deficient?

• A. Homogentisae oxidase
• B. Homogentisate dehydrogenase
• C. Tryptophan Hydroxylase
• D. Tyrosine Transaminase

Hint:

Dark/black urine on standing in a child with no intellectual disability points to a block in the tyrosine degradation pathway.

Answer 1

The Correct Option is A

Clinical diagnosis: Alkaptonuria

Pathway of tyrosine catabolism:
Tyrosine $\rightarrow$ p-hydroxyphenylpyruvate $\rightarrow$ Homogentisate $\xrightarrow{\text{Homogentisate oxidase (DEFICIENT)}}$ Maleylacetoacetate $\rightarrow$ Fumarate + Acetoacetate

In Alkaptonuria: Homogentisate oxidase is deficient $\Rightarrow$ Homogentisic acid accumulates $\Rightarrow$ excreted in urine $\Rightarrow$ oxidizes to dark pigment on standing (black urine).

Key features:
- Autosomal recessive disorder
- Garrod's Tetrad: Alkaptonuria, Albinism, Pentosuria, Cystinuria
- Urine darkening on standing is the only childhood symptom
- Ochronosis in adults: pigment deposition in intervertebral discs, nose and ear cartilage
- Arthritis
- Normal intelligence; normal life till 3rd-4th decade

Why not Tyrosine Transaminase? -- that deficiency causes Tyrosinemia Type II (Richner-Hanhart syndrome) with corneal and skin lesions.
\[\boxed{\text{Homogentisate oxidase}}\]