Paediatrics: Disorders of nucleotide metabolism

Disorders of nucleotide metabolism

A miscellaneous group of disorders characterized by abnormalities in enzymes responsible for metabolism and removal of the purine and pyrim-idine components of proteins and amino acids.

Classification of disorders of nucleotide metabolism

Disorders of purine metabolism

•   Lesch–Nyhan syndrome

•   Gout

•   Renal lithiasis (adenine phosphoribosyltransferase (APRT) deficiency)

•   Xanthinuria (xanthine oxidase deficiency)

Disorders of pyrimidine metabolism

•   Type I and II orotic aciduria

•   Ornithine transcarbamylase deficiency

Lesch–Nyhan syndrome

X-linked recessive. Due to a deficiency in hypoxanthine–guanine phospho-ribosyltransferase (HPRT) leading to the formation of excessive uric acid.

Children are normal at birth and symptoms and signs develop in the first few months. Classic clinical features include:

·Severe neurodevelopmental impairment.

• Behavioural problems including self-mutilative biting of fingers and lips.

• Spastic CP.

• Choreoathetosis.

• Uric acid urinary/renal stone development.

• Megaloblastic anaemia.

• Short stature.

• Vomiting.

Biochemical analysis demonstrates increased plasma and urinary uric acid levels. Molecular genetic testing for mutations in the HPRT gene is available.