What are the causes and symptoms of Lesch-Nyhan syndrome?

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 between families. The HPRT gene is located on the X chromosome. Since the HPRT gene is located on the X chromosome, Lesch-Nyhan syndrome is considered X-liked. This means that it 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. They are considered to be 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 any 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.

At birth, males with Lesch-Nyhan syndrome appear completely normal. Development is usually normal for the first few months. Symptoms develop between three to six months of age. Sand-like crystals of uric acid in the diapers may be one of the first symptoms of the disease. The baby may be unusually irritable. Typically, the first sign of nervous system impairment is the inability to lift their head or sit up at an appropriate age. Many patients with Lesch-Nyhan will never learn to walk. By the end of the first year, writhing motions (athetosis), and spasmodic movements of the limbs and facial muscles (chorea) are clear evidence of defective motor development.

The compulsive self-injury associated with Lesch-Nyhan syndrome begins, on average, at three years. The self-injury begins with biting of the lips and tongue. As the disease progresses, affected individuals frequently develop finger biting and head banging. The self-injury can increase during times of stress.

Males with Lesch-Nyhan disease may also develop kidney damage due to kidney stones. Swollen and tender joints(gout)is another common problem.