Lesch-Nyhan Disease (LND) Fact Sheet

First description: The first description of Lesch-Nyhan Disease may very well have been in the year 1267. Beck (Euro J of Ped Surg 1991) identified an origina l description of what is most probably LND when he uncovered cases of self-injury, gout, and menta l retardation in individuals living in a small village in England where St. Thomas, Archbishop of Canterbury, had been killed. The origina l account was written by Jacobus de Voragine from secondary sources (Golden Legend). Incidenta lly, de Voragaine thought the origin of the disease might somehow be related to the murder of St. Thomas and the “wrath of God”. More recently, in 1959, two physicians, Catel and Schmidt, described what has turned out to be the first variant of the disorder of partial HPRT deficiency (Kelley-Seegmiller syndrome) which, in turn, involves a variable degree of neurological symptoms without the self-injurious behavior of LND. The enzyme defect was discovered by Seegmiller in a patient with partial deficiency of HPRT in 1967. In 1960 Riley described gout and cerebral palsy in a 3 year old that appears to be a classic case of LND. Riley, a pediatric ian in Glasgow, cared for children with developmental disabilities at a time when such clinics were not common. Commonly accepted as the first description of the familia l nature of the disease was by Nyhan and Lesch who published data in 1964 on two brothers with LND in the American Journal of Medicine 36, 561 –570. Nyhan followed up this first artic le with a second article in 1965, A familial disorder of uric acid metabolism and central nervous system function in J of Pediatrics, 257 – 263. Hoefnagel et al, in 1965, were the first to suggest it was Xlinked. In 1983, Wilson and Kelly identified the first specific mutation at the molecular level: a single nucleotide change in the codon for aspartic acid 193 -GAC for AAC. This was the first of many different nucleotide changes identified in this gene.