Disorders of Purine Metabolism

Abstract

This chapter discusses the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency that has two clinical forms: Lesch–Nyhan syndrome (complete HGPRT deficiency) and Kelley–Seegmiller syndrome (partial HGPRT deficiency). Mutations in the X-linked HGPRT gene result in deficiencies of HGPRT enzyme activity, which may cause either a severe form of gout or Lesch–Nyhan syndrome, depending on the residual enzyme activity. Mutations leading to these diseases are heterogenous and include DNA base substitutions and splicing errors. The complete deficiency of HGPRT leads to prominent neurological disturbances in the newborn. Recurrent episodes of coma have been reported. These may be explained by the disruption of the cellular energy metabolism because of purine depletion, consequent to lack of the purine salvage pathway normally provided by the HGPRT.