Lesch-Nyhan Syndrome (LNS and HGPRT

Lesch-Nyhan Syndrome (LNS) 1. Lesch-Nyhan syndrome results from a recessive mutation on the X chromosome, in the gene for hypoxanthine-guanine phosphoribosyl transferase (HGPRT). 2. HGPRT is an enzyme essential to purine (Adenine and Guanine) utilization. In Lesch-Nyhan syndrome this pathway is highly impaired. Purines accumulate and are converted to uric acid.à Build up of uric acid. 3. The fatal disease is found in males, while heterozygous (carrier) females may show symptoms when lyonization (inactivation) of the normal X chromosome leaves the X chromosome with the defective HGPRT gene in control of cells. 4. Symptoms of Lesch-Nyhan syndrome: a. Infants develop normally for several months. Orange uric acid crystals in diapers (of males) are only clue of disease. b. At 3–8 months, motor development delays lead to weak muscles. c. Muscle tone is altered, producing uncontrollable movements and involuntary spasms. d. At 2–3 years children show bizarre activity, such as compulsive self-mutilation that is difficult to control and painful, as well as aggression toward others. e. Lesch-Nyhan individuals score severely retarded on intelligence tests, possibly due to poor communications skills. f. Most Lesch-Nyhan individuals die before their 20s, typically from infection, kidney failure or uremia.