title: Lesch-Nyhan disease in a 20-year- old man incorrectly described as developing 'cerebral palsy' after general anaesthesia in infancy.
abstract: Lesch-Nyhan disease (LND) is a rare X-linked recessive genetic disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme. The classic clinical condition is characterized by cognitive impairment, hypotonia at rest, choreoathetosis, hyperuricaemia and the hallmark symptom of severe and involuntary self-mutilation. We describe a man with LND who was initially thought to have suffered from a dyskinetic cerebral palsy after an uncomplicated inguinal herniorrhaphy under general anaesthesia at 5 1/2 months of age. In the absence of overt self-injurious behaviour, the diagnosis was not considered for nearly two decades. The diagnosis of LND was established at 20 years of age through clinical review, biochemical examinations and molecular analysis. HPRT haemolysate activity was 7.6% of the normal control, suggesting that he had a milder variant of the disease. Mutation analysis of the HPRT gene revealed a novel missense mutation, c.449T > G in exon 6 (p.V150G). Cascade testing of family members revealed that the mother was heterozygous for the mutation but two siblings (a brother and a sister) did not carry the sequence mutation. Whether the onset of neurological abnormalities in this particular case can be attributed to the general anaesthesia is discussed.
authors.affiliation: Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Chiong
authors.forename: A
authors.initials: A
authors.lastname: Marinaki
authors.forename: J
authors.initials: J
authors.lastname: Duley
authors.forename: B
authors.initials: B
authors.lastname: Bennetts
authors.forename: R
authors.initials: R
authors.lastname: Ouvrier
authors.forename: J
authors.initials: J
authors.lastname: Christodoulou
mesh_terms: D000328:Adult; D000768:Anesthesia, General / Q000009:adverse effects; D002547:Cerebral Palsy / Q000175:diagnosis* / Q000209:etiology; D003951:Diagnostic Errors; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics; D007223:Infant; D007926:Lesch-Nyhan Syndrome / Q000175:diagnosis*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase