From the FDA Drug Label
Allopurinol acts on purine catabolism, without disrupting the biosynthesis of purines. It reduces the production of uric acid by inhibiting the biochemical reactions immediately preceding its formation. Two of the patients had Lesch-Nyhan syndrome, which is characterized by excessive uric acid production combined with a deficiency of the enzyme, hypoxanthineguanine phosphoribosyltransferase (HGPRTase)
The 6-year-old boy with Lesch-Nyhan syndrome has elevated levels of Uric acid.
- The condition is characterized by excessive uric acid production.
- This is due to a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) 1
From the Research
A 6-year-old boy with Lesch-Nyhan syndrome would have elevated levels of uric acid. Lesch-Nyhan syndrome is a rare X-linked recessive disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which plays a crucial role in the purine salvage pathway. Without this enzyme, the body cannot recycle purines properly, leading to excessive production of uric acid. This elevated uric acid can cause symptoms such as gouty arthritis, kidney stones, and neurological manifestations including self-mutilating behaviors, choreoathetosis, and cognitive impairment. The diagnosis is typically confirmed by measuring HGPRT enzyme activity in cells and genetic testing for mutations in the HPRT1 gene, as described in the study by 2. Treatment focuses on managing hyperuricemia with medications like allopurinol to prevent complications, though this doesn't address the neurological symptoms of the disorder. Some key points to consider in the management of Lesch-Nyhan syndrome include:
- Uric acid overproduction is present in all HPRT-deficient patients and is associated with lithiasis and gout, as noted in the study by 2.
- Neurological manifestations include severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit, and self-injurious behaviour, as described in the study by 3.
- The lack of precise understanding of the neurological dysfunction has precluded development of useful therapies, as mentioned in the study by 2.
- Spasticity, when present, and dystonia can be managed with benzodiazepines and gamma-aminobutyric acid inhibitors such as baclofen, as recommended in the study by 2. Overall, the management of Lesch-Nyhan syndrome requires a comprehensive approach that addresses both the metabolic and neurological aspects of the disorder.