Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency.
Disease management
HND
HPRT deficiency
Hyperuricemia
Lesch-Nyhan disease
Prognosis
Journal
Molecular genetics and metabolism
ISSN: 1096-7206
Titre abrégé: Mol Genet Metab
Pays: United States
ID NLM: 9805456
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
08
02
2019
revised:
31
05
2019
accepted:
01
06
2019
pubmed:
12
6
2019
medline:
18
4
2020
entrez:
12
6
2019
Statut:
ppublish
Résumé
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. Genetic and clinical features of French and Italian patients with a confirmed diagnosis of HPRT deficiency were collected. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31182398
pii: S1096-7192(19)30131-3
doi: 10.1016/j.ymgme.2019.06.001
pii:
doi:
Substances chimiques
Hypoxanthine Phosphoribosyltransferase
EC 2.4.2.8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
147-157Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.