Lesch-Nyhan Syndrome

Excerpt

Lesch Nyhan syndrome is an inborn disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme, an enzyme of the purine salvage pathway. The enzyme is responsible for recycling purines by converting guanine and hypoxanthine into guanosine monophosphate and inosine monophosphate, respectively. Lack of the enzyme causes an increase in guanine and hypoxanthine, which eventually is converted into uric acid. HPRT deficiency results in a spectrum of clinical presentations depending on the severity of enzyme deficiency. With an enzyme activity of less than 1.5%, Lesch Nyhan falls towards the severe end of the spectrum. The characteristics defining the disease are hyperuricemia, neurodevelopmental abnormalities with global developmental delay, involuntary movements, and self-injurious behavior. Other less severe variants include HPRT related hyperuricemia, also known as Keeley–Seegmiller syndrome (enzyme activity 8% to 60%, and only hyperuricemia related symptoms), and hyperuricemia with neurological disability (enzyme activity 1.5 to 2% with hyperuricemia symptoms and neurological symptoms like dystonia, choreoathetosis, spasticity, intellectual disability).