Lesch-Nyhan syndrome is a genetic disease that results in abnormalities of the nervous system and increased production of uric acid (a waste product of body metabolism).
It is due to mutations in the HPRT1 gene. This gene originally allows the body to make the enzyme Hypoxanthine Guanine Phosphoribosyl Transferase 1 (HGPRTase), an enzyme that prevents the breakdown of Purines (DNA and RNA building blocks). When the HPRT1 gene is mutated, the body cannot make HGPRTase, therefore, purines are broken down and cannot be used to make DNA and RNA. The product of purine breakdown is uric acid.
The reason people with Lesch-Nyhan syndrome have nervous system abnormalities is unknown but scientists have proposed that it may be due to a reduction in the activation of dopamine receptors in the body seen in this disease. Dopamine is a major neurotransmitter of the nervous system and when its receptors are not working well, malfunctions of the brain and nervous system would be observed.
It is more common in males because it is normally inherited from the X chromosome and males have just one copy of the X chromosome.
The symptoms of Lesch-Nyhan syndrome include:
- Poor kidney function
- Pain radiating from the back to the groin due to kidney stones
- Painful swollen joints (gout)
- Involuntary muscle movements
- Orange “sand” in the diaper of babies due to uric acid in the urine
- Intellectual disability
- Self-mutilating behaviors such as lip biting and finger biting
- Difficulty swallowing and/or vomiting
The most common symptom of Lesch-Nyhan syndrome is self-mutilation, which usually begins in the first 3 years of life, although could occur later.
The treatment of Lesch-Nyhan syndrome is directed at the various symptoms:
- Behavioral modification is used to reduce self-mutilating behaviors
- Some drugs such as Valproate, Gabapentin, and Baclofen may also be used to reduce nervous system dysfunction.
- Allopurinol of Febuxostat are drugs used to reduce the production of uric acid
- If kidney stones are present, they would be removed either by surgery or by delivery of shockwaves to break up the stones into small pieces so they can be passed with the urine.
- Families of children who have Lesch-Nyan syndrome are advised to go for genetic counseling.