Severe changes (mutations) in the HPRT gene completely halt the activity of the enzyme HPRT. There have been many different severe mutations identified in the HPRT gene. These mutations may be different within families. Since the HPRT gene is located on the X chromosome, Lesch-Nyhan syndrome is considered an X-linked disorder and therefore only affects males.
A person's sex is determined by their chromosomes. Males have one X chromosome and one Y chromosome. Females, on the other hand, have two X chromosomes. Males who possess a severe mutation in their HPRT gene will develop Lesch-Nyhan syndrome. Females who possess a severe mutation in their HPRT gene will not; instead they are carriers. This is because females have another X chromosome without the mutation that prevents them from getting this disease. If a woman is a carrier, she has a 50% risk with each pregnancy to pass on her X chromosome with the mutation. Therefore, with every male pregnancy she has a 50% risk to have an affected son, and with every female pregnancy she has a 50% risk to have a daughter who is a carrier.
Lesch-Nyhan syndrome affects approximately one in 380,000 live births. It occurs evenly among races. Almost always, only male children are affected. Women carriers usually do not have any symptoms. Women carriers can occasionally develop inflammation of the joints (gout)as they get older.
Holly Ann Ishmael MS, CGC, Thomson Gale, Gale, Detroit,