Attenuated variants of Lesch-Nyhan disease

H. A. Jinnah, Irene Ceballos-Picot, Rosa J. Torres, Jasper E. Visser, David Schretlen, Alfonso Verdu, Laura E. Laróvere, Chung Jen Chen, Antonello Cossu, Chien Hui Wu, Radhika Sampat, Shun Jen Chang, Raquel Dodelson De Kremer, William Nyhan, James C O Harris, Stephen G. Reich, Juan G. Puig

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)671-689
Number of pages19
JournalBrain
Volume133
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

Lesch-Nyhan Syndrome
Uric Acid
Self-Injurious Behavior
Dystonia
Neurologic Manifestations
Cognition
Phenotype
Enzymes

Keywords

  • Behaviour
  • Dystonia
  • Genotype-phenotype correlation
  • Kelly-Seegmiller syndrome
  • Metabolic disease
  • Neurogenetics
  • Uric acid

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Jinnah, H. A., Ceballos-Picot, I., Torres, R. J., Visser, J. E., Schretlen, D., Verdu, A., ... Puig, J. G. (2010). Attenuated variants of Lesch-Nyhan disease. Brain, 133(3), 671-689. https://doi.org/10.1093/brain/awq013

Attenuated variants of Lesch-Nyhan disease. / Jinnah, H. A.; Ceballos-Picot, Irene; Torres, Rosa J.; Visser, Jasper E.; Schretlen, David; 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 O; Reich, Stephen G.; Puig, Juan G.

In: Brain, Vol. 133, No. 3, 03.2010, p. 671-689.

Research output: Contribution to journalArticle

Jinnah, HA, Ceballos-Picot, I, Torres, RJ, Visser, JE, Schretlen, D, Verdu, A, Laróvere, LE, Chen, CJ, Cossu, A, Wu, CH, Sampat, R, Chang, SJ, De Kremer, RD, Nyhan, W, Harris, JCO, Reich, SG & Puig, JG 2010, 'Attenuated variants of Lesch-Nyhan disease', Brain, vol. 133, no. 3, pp. 671-689. https://doi.org/10.1093/brain/awq013
Jinnah HA, Ceballos-Picot I, Torres RJ, Visser JE, Schretlen D, Verdu A et al. Attenuated variants of Lesch-Nyhan disease. Brain. 2010 Mar;133(3):671-689. https://doi.org/10.1093/brain/awq013
Jinnah, H. A. ; Ceballos-Picot, Irene ; Torres, Rosa J. ; Visser, Jasper E. ; Schretlen, David ; 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 O ; Reich, Stephen G. ; Puig, Juan G. / Attenuated variants of Lesch-Nyhan disease. In: Brain. 2010 ; Vol. 133, No. 3. pp. 671-689.
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