Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency

Annalisa Madeo, Maja Di Rocco, Anaïs Brassier, Nadia Bahi-Buisson, Pascale De Lonlay, Irène Ceballos-Picot

Research output: Contribution to journalArticle


BACKGROUND: HPRT deficiency is a rare disorder of purine metabolism whose natural history is not fully understood. No optimal management recommendations exist. The objective of the present study is to characterize a large cohort of patients with HPRT deficiency, comparing Lesch-Nyhan Disease (LND) and its attenuated variants, with the purpose of helping clinicians in disease management and prognostic definition.

METHODS: Genetic and clinical features of French and Italian patients with a confirmed diagnosis of HPRT deficiency were collected.

RESULTS: A hundred and one patients were studied, including 66 LND, 22 HND (HPRT-related Neurological Dysfunction) and 13 HRH (HPRT-Related Hyperuricemia) patients. The clinical manifestations at onset were not specific, but associated with an orange coloration of diapers in 22% of patients. The overall neurological involvement was more severe in LND than in HND patients. Behavioural disturbances were not limited to self-injuries and were not exclusive of LND. Median age of involuntary movements and self-injuries appearance in LND was 1.0 and 3 years, respectively. Renal manifestations (66.3% of patients) occurred at any age with a median onset age of 1.1 years, while gout (25.7% of patients) appeared later in disease course (median onset age 18 years) and was more frequent in attenuated variants than in LND. HPRT activity and genotype showed a significant correlation with the severity of the neurological disease. On the contrary, there were no significant differences in the development of nephropathy or gout. For the treatment of neurological aspects, botulinum toxin injections, oral or intrathecal baclofen and gabapentin were partially efficacious and well tolerated, while deep brain stimulation was associated to a worsening of patients' condition.

CONCLUSIONS: The present study improves the knowledge of the natural history of HPRT deficiency and could represent a starting point for the development of future management guidelines.

Original languageEnglish
Pages (from-to)147-157
Number of pages11
JournalMolecular Genetics and Metabolism
Issue number2
Publication statusPublished - Jun 2019

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