Lesch-Nyhan disease is an X-linked inborn error of metabolism caused by a deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT).
Characterized by hyperuricemia and a typical neurobehavioral phenotype, including a hyperkinetic movement disorder dominated by dystonia, attentional deficits, and behavioral disturbances with self-injury.
Should be considered when delayed development is accompanied by a hyperkinetic movement disorder, including dystonia, particularly when routine brain MRI is normal.
Should be suspected if a delayed development is accompanied by self-injurious behavior or evidence of excessive production of uric acid.
Diagnosis is based on HPRT enzyme activity, preferably measured in live cells such as cultured fibroblasts, and on molecular genetic techniques demonstrating the gene mutation. Results might provide predictive clues about ultimate disease severity.
Currently, no curative treatment is available. Supportive care includes muscle relaxants for the movement disorder, and physical restraints or teeth extraction to prevent self-injury.
Lesch-Nyhan disease (LND) is an X-linked inborn error of metabolism, caused by a mutation in the gene encoding the purine recycling enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). The first description was in 1964, when two brothers originally diagnosed with cerebral palsy were later recognized as living with a previously undescribed inherited metabolic disease because of the familial occurrence and unusual clinical features. HPRT deficiency causes overproduction of uric acid, which may lead to hyperuricemia, nephrolithiasis, gouty arthritis, and subcutaneous tophi. In addition, patients exhibit a distinctive neurobehavioral phenotype, characterized by dystonia, attentional deficits, and behavioral disturbances including self-injury, presumably attributable to dysfunction of the basal ganglia dopamine system. Patients with a partial enzyme deficiency (Lesch-Nyhan variants [LNV]) display an incomplete phenotype: overproduction of uric acid with or without neurologic dysfunction, and no self-injury.
History and exam
Key diagnostic factors
- age <12 months
- orange "sand" crystals in diaper
- kidney stones
- pyramidal signs
- testicular atrophy
- male sex
- developmental delay
- involuntary movements
- generalized hypotonia
- self-injurious behavior, usually at <5 years of age
- self-injurious behavior focusing on the mouth and fingers
- cognitive disturbances
- delayed growth
- action dystonia
- positive family history
- positive family history
1st investigations to order
- serum uric acid level
- 24-hour urinary uric acid excretion
- hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene analysis
- HPRT enzyme activity
Investigations to consider
- brain MRI
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