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Attenuated variants of Lesch-Nyhan disease
Lesch–Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine–guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842514/ https://www.ncbi.nlm.nih.gov/pubmed/20176575 http://dx.doi.org/10.1093/brain/awq013 |
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author | Jinnah, H. A. Ceballos-Picot, Irene Torres, Rosa J. Visser, Jasper E. Schretlen, David J. Verdu, Alfonso Laróvere, Laura E. Chen, Chung-Jen Cossu, Antonello Wu, Chien-Hui Sampat, Radhika Chang, Shun-Jen de Kremer, Raquel Dodelson Nyhan, William Harris, James C. Reich, Stephen G. Puig, Juan G. |
author_facet | Jinnah, H. A. Ceballos-Picot, Irene Torres, Rosa J. Visser, Jasper E. Schretlen, David J. Verdu, Alfonso Laróvere, Laura E. Chen, Chung-Jen Cossu, Antonello Wu, Chien-Hui Sampat, Radhika Chang, Shun-Jen de Kremer, Raquel Dodelson Nyhan, William Harris, James C. Reich, Stephen G. Puig, Juan G. |
author_sort | Jinnah, H. A. |
collection | PubMed |
description | Lesch–Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine–guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the classic disease, variant forms of the disease occur wherein some clinical features are absent or unusually mild. The current studies provide the results of a prospective and multi-centre international study focusing on neurological manifestations of the largest cohort of Lesch–Nyhan disease variants evaluated to date, with 46 patients from 3 to 65 years of age coming from 34 families. All had evidence for overproduction of uric acid. Motor abnormalities were evident in 42 (91%), ranging from subtle clumsiness to severely disabling generalized dystonia. Cognitive function was affected in 31 (67%) but it was never severe. Though none exhibited self-injurious behaviours, many exhibited behaviours that were maladaptive. Only three patients had no evidence of neurological dysfunction. Our results were compared with a comprehensive review of 78 prior reports describing a total of 127 Lesch–Nyhan disease variants. Together these results define the spectrum of clinical features associated with hypoxanthine–guanine phosphoribosyltransferase deficiency. At one end of the spectrum are patients with classic Lesch–Nyhan disease and the full clinical phenotype. At the other end of the spectrum are patients with overproduction of uric acid but no apparent neurological or behavioural deficits. Inbetween are patients with varying degrees of motor, cognitive, or behavioural abnormalities. Recognition of this spectrum is valuable for understanding the pathogenesis and diagnosis of all forms of hypoxanthine–guanine phosphoribosyltransferase deficiency. |
format | Text |
id | pubmed-2842514 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28425142010-03-22 Attenuated variants of Lesch-Nyhan disease Jinnah, H. A. Ceballos-Picot, Irene Torres, Rosa J. Visser, Jasper E. Schretlen, David J. Verdu, Alfonso Laróvere, Laura E. Chen, Chung-Jen Cossu, Antonello Wu, Chien-Hui Sampat, Radhika Chang, Shun-Jen de Kremer, Raquel Dodelson Nyhan, William Harris, James C. Reich, Stephen G. Puig, Juan G. Brain Original Articles Lesch–Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine–guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the classic disease, variant forms of the disease occur wherein some clinical features are absent or unusually mild. The current studies provide the results of a prospective and multi-centre international study focusing on neurological manifestations of the largest cohort of Lesch–Nyhan disease variants evaluated to date, with 46 patients from 3 to 65 years of age coming from 34 families. All had evidence for overproduction of uric acid. Motor abnormalities were evident in 42 (91%), ranging from subtle clumsiness to severely disabling generalized dystonia. Cognitive function was affected in 31 (67%) but it was never severe. Though none exhibited self-injurious behaviours, many exhibited behaviours that were maladaptive. Only three patients had no evidence of neurological dysfunction. Our results were compared with a comprehensive review of 78 prior reports describing a total of 127 Lesch–Nyhan disease variants. Together these results define the spectrum of clinical features associated with hypoxanthine–guanine phosphoribosyltransferase deficiency. At one end of the spectrum are patients with classic Lesch–Nyhan disease and the full clinical phenotype. At the other end of the spectrum are patients with overproduction of uric acid but no apparent neurological or behavioural deficits. Inbetween are patients with varying degrees of motor, cognitive, or behavioural abnormalities. Recognition of this spectrum is valuable for understanding the pathogenesis and diagnosis of all forms of hypoxanthine–guanine phosphoribosyltransferase deficiency. Oxford University Press 2010-03 2010-02-22 /pmc/articles/PMC2842514/ /pubmed/20176575 http://dx.doi.org/10.1093/brain/awq013 Text en © The Author(s) 2010. Published by Oxford University Press on behalf of Brain. http://creativecommons.org/licenses/by-nc/2.5/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Jinnah, H. A. Ceballos-Picot, Irene Torres, Rosa J. Visser, Jasper E. Schretlen, David J. Verdu, Alfonso Laróvere, Laura E. Chen, Chung-Jen Cossu, Antonello Wu, Chien-Hui Sampat, Radhika Chang, Shun-Jen de Kremer, Raquel Dodelson Nyhan, William Harris, James C. Reich, Stephen G. Puig, Juan G. Attenuated variants of Lesch-Nyhan disease |
title | Attenuated variants of Lesch-Nyhan disease |
title_full | Attenuated variants of Lesch-Nyhan disease |
title_fullStr | Attenuated variants of Lesch-Nyhan disease |
title_full_unstemmed | Attenuated variants of Lesch-Nyhan disease |
title_short | Attenuated variants of Lesch-Nyhan disease |
title_sort | attenuated variants of lesch-nyhan disease |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842514/ https://www.ncbi.nlm.nih.gov/pubmed/20176575 http://dx.doi.org/10.1093/brain/awq013 |
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