Lesch-nyhan variant syndrome: Variable presentation in 3 affected family members

Kyriakie Sarafoglou, Krista Grosse-Redlinger, Christopher J. Boys, Laurence Charnas, Noelle Otten, Robyn Broock, William L. Nyhan

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background: Lesch-Nyhan disease is an inborn error of purine metabolism that results from deficiency of the activity of hypoxanthine phosphoribosyltransferase (HPRT). The heterogeneity of clinical phenotypes seen in HPRT deficiency corresponds to an inverse relationship between HPRT enzyme activity and clinical severity. With rare exception, each mutation produces a stereotypical pattern of clinical disease; onset of neurologic symptoms occurs during infancy and is thought to be nonprogressive. Objective: To document a family in which a single HPRT gene mutation has led to 3 different clinical and enzymatic phenotypes. Design: Case report. Settings: A university-based outpatient metabolic clinic and a biochemical genetics laboratory. Patients: Three males (2 infants and their grandfather) from the same family with Lesch-Nyhan variant, including one of the oldest patients with Lesch-Nyhan variant at diagnosis (65 years). Main Outcome Measures: Clinical and biochemical observations. Results: Sequencing of 5 family members revealed a novel mutation c.550G>T in exon 7 of the HPRT gene. The considerably variable clinical phenotype corresponded with the variable enzymatic activity in the 3 males, with the grandfather being the most severely affected. Conclusions: The different phenotypes encountered in the enzymatic analysis of cultured fibroblasts from a single mutation in the same family is unprecedented. The significant decrease in the grandfather's HPRT enzymatic activity compared with that of his grandchildren could be a function of the Hayflick Limit Theory of cell senescence.

Original languageEnglish (US)
Pages (from-to)761-764
Number of pages4
JournalArchives of Neurology
Issue number6
StatePublished - Jun 2010


  • Lesch-nyhan
  • Inborn errors of metabolism


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