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.
• Lesch–Nyhan syndrome
• Renal lithiasis (adenine phosphoribosyltransferase (APRT) deficiency)
• Xanthinuria (xanthine oxidase deficiency)
• Type I and II orotic aciduria
• Ornithine transcarbamylase deficiency
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.
• Uric acid urinary/renal stone development.
• Megaloblastic anaemia.
• Short stature.
Biochemical analysis demonstrates increased plasma and urinary uric acid levels. Molecular genetic testing for mutations in the HPRT gene is available.