Lesha-Nyhan Syndrome

Lesha Nyhan syndrome

**Lesch Nyhan syndrome,** a hereditary degenerative disease from the group of lysosomal disorders with an autosomal recessive type of transmission, associated with a defect in the lysosomal enzyme hypoxanthine-guanine phosphoribosyltransferase, an enzyme that provides one of the final reactions of purine metabolism. Named after the American pediatricians M.I. Lesh (1912–1977), who was the first to describe it in 1962, and A.L. Nyhan, who identified its clinically isolated syndrome. In most patients, the _LGALT_ gene mutation remains completely penetrant, although cases of pure inactivity of this enzyme have also been described. Currently, more than 41 defects in the _LGALT gene have been identified. Phenocopying similarities of Lesch-Nyhan syndrome with other diseases accompanied by a deficiency of the lysosomal level of purine nucleotide phosphorylase (for example, Farber disease) have been discovered. There are two main clinical variants of Lesch-Nyhan syndrome: the so-called classic and “modified”. According to Russian literature and materials from a genetic study of Russian patients, most children with the classic variant of the syndrome have a defect in a single gene copy linked to chromosome 15 or the X chromosome, formed as a result of a pericentric or interchromosomal mutation characteristic of a classic familial duplication deletion. The classic version is characterized by normal integral activity of GGPT in peripheral blood leukocytes (350–450%), increasing during the first year of life to 900–800%, followed by a sharp decrease in enzyme activity to normal levels and a progressive course of degenerative processes in all tissues of the child’s body. Similar data were obtained for plasma indicators: GGPT activity is determined from 60 to 250% normally, reaches a maximum in the first 2 years of life and sharply decreases. The “modified” version of the syndrome is inherited in an autosomal recessive manner, the clinical picture is identical to the classic version. According to some domestic authors, there is a third genetic form of the syndrome, the inheritance of which is also associated with the presence of genetic defects in various genes encoding PURINGUANINE PHOSPHORIBOSYLTRANSFERASE AND GUANASINURIDINOSIDE FORBOPOYRIDOSE TRANSFERASE ENZYMES. Some authors identify the so-called monostimulant form of the disease, caused by the presence of a single functional copy of the gene with a mutation. Perhaps it will become an independent nosological unit. This is confirmed by modern ideas about the heterogeneity of purine nucleoside phosphorylibosides, considered as separate nosological forms. The clinical picture of the syndrome includes three groups of disorders: osteoarticular and pathological psychology. The most specific signs are ataxia, mental retardation, retardation,