Investigations
1st investigations to order
serum uric acid level
Test
Elevated in most patients, but because of rapid renal clearance serum uric acid levels may be normal at the time of testing.[3][22]May be part of a metabolic work-up in patients who present with developmental delay and hypotonia (thus prompting consideration of Lesch-Nyhan disease [LND]).[Figure caption and citation for the preceding image starts]: Uric acid levels in patients with classic Lesch-Nyhan disease (LND), patients with Lesch-Nyhan variants (LNV), and healthy controls. SD, standard deviation; HRH: hypoxanthine-guanine phosphoribosyltransferase (HPRT)-related hyperuricemia; HRD: HPRT-related neurological diseaseFrom the collection of J.E. Visser, MD, PhD and H.A. Jinnah, MD, PhD; used with permission [Citation ends].
Result
elevated
24-hour urinary uric acid excretion
Test
A spot (or random) urine sample for uric acid is not reliable because uric acid values vary with diet, hydration, and a number of other factors. A 24-hour urinary uric acid level is, therefore, more reliable, especially if it is normalised to body mass by determining the uric acid-creatinine ratio. However, complete 24-hour specimens are notoriously hard to collect, especially in children.
Result
elevated
hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene analysis
Test
Usually performed after measurement of uric acid levels, and often combined with HPRT enzyme activity, but may be the first test ordered in cases of high clinical suspicion or known HPRT mutation in the family. Mutations might provide clues about disease severity.
Result
mutation in the coding region of the HPRT gene
HPRT enzyme activity
Test
HPRT activities in cultured live cells (fibroblasts) are considered more reliable than those in cell lysates, owing to possible kinetic and stability properties of mutant HPRT enzyme.[3]
Result
reduced; typical values (% of normal): classic LND <1.5%; hyperuricaemia with neurological dysfunction (HRND) <8%; HPRT-related hyperuricaemia (HRH) ≥8%
Investigations to consider
brain MRI
Test
Brain imaging is not normally necessary for diagnosis and management of Lesch-Nyhan disease, but may be helpful if there is clinical suspicion of other diagnoses.
Generally, neither CT scanning nor MRI reveals any obvious structural malformations or signal changes.[22][30] Routine imaging is usually normal, but may reveal mild loss of brain volume.[31]
Result
may reveal mild loss of brain volume
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