Which are the causes of Lesch-Nyhan Syndrome?

Lesch-Nyhan Syndrome (LNS) is a rare genetic disorder that primarily affects males. It is caused by a mutation in the HPRT1 gene, which is responsible for producing an enzyme called hypoxanthine-guanine phosphoribosyltransferase (HGprt). This enzyme plays a crucial role in the recycling of purines, which are essential building blocks of DNA and RNA.

The mutation in the HPRT1 gene leads to a deficiency or complete absence of HGprt enzyme activity. As a result, the body is unable to properly recycle purines, leading to an accumulation of uric acid in the body. Uric acid is a waste product that is normally excreted in urine, but in individuals with LNS, its levels become abnormally high.

There are several possible causes of Lesch-Nyhan Syndrome:

1. Inherited Mutation: Lesch-Nyhan Syndrome is an inherited disorder that follows an X-linked recessive pattern. This means that the mutation is located on the X chromosome, and males are more commonly affected because they have only one X chromosome. Females can also be carriers of the mutation but are typically unaffected due to the presence of a normal copy of the gene on their other X chromosome.

2. Spontaneous Mutation: In some cases, the mutation in the HPRT1 gene occurs spontaneously during early embryonic development. This means that the mutation is not inherited from either parent but arises as a random event. Spontaneous mutations are rare but can still result in the development of Lesch-Nyhan Syndrome.

3. Genetic Carrier: In families with a history of Lesch-Nyhan Syndrome, individuals who carry a single copy of the mutated gene are known as genetic carriers. Carriers do not exhibit symptoms of the disorder but can pass the mutated gene to their children. If both parents are carriers, there is a 25% chance with each pregnancy that their child will inherit two copies of the mutated gene and develop Lesch-Nyhan Syndrome.

4. Gene Deletion: In rare cases, a large deletion or rearrangement of genetic material involving the HPRT1 gene can cause Lesch-Nyhan Syndrome. These deletions can occur spontaneously or be inherited from a parent who carries the deletion.

It is important to note that the exact mechanisms by which the mutation in the HPRT1 gene leads to the specific symptoms of Lesch-Nyhan Syndrome are not fully understood. However, the deficiency of HGprt enzyme activity and the subsequent accumulation of uric acid are believed to play a significant role in the development of the characteristic features of the disorder.

Lesch-Nyhan Syndrome is characterized by:

• Neurological Symptoms: Individuals with LNS often exhibit severe neurological symptoms, including intellectual disability, developmental delays, spasticity (stiffness and involuntary muscle contractions), and dystonia (involuntary muscle movements).


• Self-Injurious Behavior: One of the most distinctive features of Lesch-Nyhan Syndrome is the presence of self-injurious behavior. This includes biting of the lips, fingers, and cheeks, as well as head banging and self-hitting. The exact cause of this behavior is not fully understood, but it is believed to be related to abnormalities in the basal ganglia, a region of the brain involved in motor control and behavior.


• Hyperuricemia: Elevated levels of uric acid in the blood and urine are a hallmark of Lesch-Nyhan Syndrome. This can lead to the development of gout, a painful condition characterized by the deposition of uric acid crystals in the joints.


• Kidney Stones: The accumulation of uric acid can also result in the formation of kidney stones, which can cause severe pain and potentially lead to kidney damage if left untreated.

In conclusion, Lesch-Nyhan Syndrome is primarily caused by a mutation in the HPRT1 gene, leading to a deficiency of the HGprt enzyme and subsequent accumulation of uric acid. The disorder can be inherited or occur spontaneously due to a genetic mutation. While the exact mechanisms underlying the specific symptoms of Lesch-Nyhan Syndrome are not fully understood, the neurological symptoms, self-injurious behavior, hyperuricemia, and kidney stones are characteristic features of the disorder.