About this item:
228 Views | 142 Downloads
Author Notes:
Correspondance to: H. A. Jinnah, M.D., Ph.D., Professor, Departments of Neurology, Human Genetics & Pediatrics, Emory University, Suite 6300 Woodruff Memorial Building, 101 Woodruff Circle, Atlanta GA, 30322, Phone: 404-727-9107, Fax: 404-712-8576, hjinnah@emory.edu
Subjects:
Research Funding:
This work was supported in part by the Lesch-Nyhan Syndrome Children’s Research Foundation and NIH grant HD053312.
Keywords:
- Science & Technology
- Life Sciences & Biomedicine
- Endocrinology & Metabolism
- Genetics & Heredity
- Medicine, Research & Experimental
- Research & Experimental Medicine
- Lesch-Nyhan disease
- Lesch-Nyhan variant
- Genotype
- Phenotype
- URIC-ACID METABOLISM
- PURINE BIOSYNTHESIS
- FAMILIAL DISORDER
- HPRT DEFICIENCY
- HYPOXANTHINE
- ALLOPURINOL
- XANTHINE
- MUTATIONS
- PATIENT
Genotypic and phenotypic spectrum in attenuated variants of Lesch-Nyhan disease
Abstract:
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 phenotype includes 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.
Copyright information:
© 2014 Elsevier Inc.
This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).
