Neurocognitive functioning in Lesch-Nyhan disease and partial 
hypoxanthine-guanine phosphoribosyltransferase deficiency

Schretlen, David J.; Harris, James C.; Park, Karen Sophia; Jinnah, Hyder A.; Ojeda, Natalia

doi:10.1017/s135561770177703x

Cited by 54 publications

(43 citation statements)

References 34 publications

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“…The neurobehavioral phenotype also includes severe motor disability that resembles dystonic cerebral palsy [18,48]. Most patients also have mild or moderate neurocognitive abnormalities with intellectual disability and IQ scores in the 55–75 range, but severe mental retardation is uncommon [1,24,37,41]. …”

Section: Spectrum Of Clinical Phenotypesmentioning

confidence: 99%

Genotypic and phenotypic spectrum in attenuated variants of Lesch–Nyhan disease

Chen

Jinnah

2014

Molecular Genetics and Metabolism

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Lesch-Nyhan disease and its attenuated variants are caused by deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt). All patients exhibit excessive production of uric acid, which increases the risk for nephrolithiasis, renal failure, gouty arthritis and tophi. The mildest phenotypes include only problems related to overproduction of uric acid. The most severe clinical phenotype includes prominent neurological abnormalities and the universal feature is self-injurious behavior. In between the mildest and most severe syndromes is a broad spectrum of phenotypes with varying degrees of neurological, neurocognitive and behavioral abnormalities. The effect of HPRT1 gene mutations on residual HGprt enzyme activity is the most relevant factor contributing to disease phenotype. Attenuated clinical phenotypes are associated with residual enzyme function, whereas the most severe phenotype is usually associated with null activity. In cases of gouty arthritis with urate overproduction, a careful evaluation for motor impairments or neurocognitive abnormalities may help to identify attenuated variants of Lesch-Nyhan disease for better management.

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Section: Spectrum Of Clinical Phenotypesmentioning

confidence: 99%

Genotypic and phenotypic spectrum in attenuated variants of Lesch–Nyhan disease

Chen

Jinnah

2014

Molecular Genetics and Metabolism

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“…The third major element of the clinical phenotype is a peculiar neuropsychological profile (Nyhan, 1976; Schretlen et al, 2001, 2005). The most characteristic problem is recurrent self-injurious behavior with biting of the digits, lips, or buccal mucosa.…”

Section: Lesch–nyhan Diseasementioning

confidence: 99%

Metabolic disorders of purine metabolism affecting the nervous system

Jinnah

Sabina

Berghe

2013

Handbook of Clinical Neurology

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“…The motor impairments are dominated by dystonia, but are sometimes accompanied by choreoathetosis or spasticity [4]. Neurocognitive disability also occurs, but usually it is not severe [5–7]. …”

Section: Introductionmentioning

confidence: 99%

Clinical severity in Lesch–Nyhan disease: The role of residual enzyme and compensatory pathways

Sutcliffe

Zhao

et al. 2015

Molecular Genetics and Metabolism

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Mutations in the HPRT1 gene, which encodes the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), cause Lesch-Nyhan disease (LND) and more mildly affected Lesch-Nyhan variants. Prior studies have suggested a strong correlation between residual hypoxanthine recycling activity and disease severity. However, the relevance of guanine recycling and compensatory changes in the de novo synthesis of purines have received little attention. In the current studies, fibroblast cultures were established for 21 healthy controls and 36 patients with a broad spectrum of disease severity related to HGprt deficiency. We assessed hypoxanthine recycling, guanine recycling, steady-state purine pools, and de novo purine synthesis. There was a strong correlation between disease severity and either hypoxanthine or guanine recycling. Intracellular purines were normal in the HGprt-deficient fibroblasts, but purine wasting was evident as increased purine metabolites excreted from the cells. The normal intracellular purines in the HGprt-deficient fibroblasts was likely due in part to a compensatory increase in purine synthesis, as demonstrated by a significant increase in purinosomes. However, the increase in purine synthesis did not appear to correlate with disease severity. These results refine our understanding of the potential sources of phenotypic heterogeneity in LND and its variants.

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Neurocognitive functioning in Lesch-Nyhan disease and partial hypoxanthine-guanine phosphoribosyltransferase deficiency

Cited by 54 publications

References 34 publications

Genotypic and phenotypic spectrum in attenuated variants of Lesch–Nyhan disease

Genotypic and phenotypic spectrum in attenuated variants of Lesch–Nyhan disease

Metabolic disorders of purine metabolism affecting the nervous system

Clinical severity in Lesch–Nyhan disease: The role of residual enzyme and compensatory pathways

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