Lesch-Nyhan Syndrome
Description
Lesch-Nyhan Syndrome (LNS) is a rare, X-linked recessive genetic disorder that primarily affects males. This disorder is characterized by a deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This deficiency leads to a buildup of uric acid in the body, resulting in a range of symptoms, including self-injurious behavior, intellectual disability, and neurological complications.
Genes Involved
The gene responsible for Lesch-Nyhan Syndrome is called HPRT1, located on the X chromosome. Mutations in this gene lead to the deficiency of the HGPRT enzyme.
Recognizing the Signs and Symptoms
Recognizing the Signs and Symptoms of Lesch-Nyhan Syndrome:
- Self-injurious behavior: This is a hallmark symptom and often involves biting of lips, fingers, and even the tongue. It can be severe and difficult to manage.
- Intellectual disability: Individuals with LNS often experience varying degrees of intellectual disability, ranging from mild to severe.
- Movement problems: These include difficulties with coordination, muscle weakness, and spasticity.
- Gouty arthritis: The buildup of uric acid can cause painful inflammation in the joints.
- Kidney stones: The excess uric acid can lead to the formation of kidney stones.
- Orange-colored urine: This is due to the high levels of uric acid in the urine.
- Delayed development: Infants with LNS may experience developmental delays, including delayed milestones like walking and talking.
- Behavioral issues: Other behavioral issues may include aggression, irritability, and hyperactivity.
Causes
Lesch-Nyhan Syndrome is caused by a mutation in the HPRT1 gene. This gene provides instructions for making the HGPRT enzyme, which is involved in the breakdown of purine nucleotides, a type of building block for DNA and RNA. Without a functional HGPRT enzyme, these nucleotides break down into uric acid, which builds up in the body.
Inheritance/recurrence risk
Inheritance and Recurrence Risk:
Lesch-Nyhan Syndrome is an X-linked recessive disorder, meaning it is carried on the X chromosome. Males are more likely to develop the disorder because they only have one X chromosome. Females, having two X chromosomes, are less likely to be affected because they have a backup copy of the gene.
If a mother carries the mutated gene, there is a 50% chance of her son inheriting the disorder. Daughters have a 50% chance of being carriers themselves, but they usually don‘t experience any symptoms.
The recurrence risk for a couple with a child with LNS is also 50% for each future pregnancy.
