Lesch-Nyhan Syndrome

Lesch-Nyhan syndrome is a rare genetic disorder that causes your body to produce too much uric acid. Uric acid is a waste product that normally leaves your body through urine. When levels get too high, it can damage your kidneys, joints, and nervous system.

This condition is caused by a missing or faulty enzyme called hypoxanthine-guanine phosphoribosyltransferase, or HGPRT. Without this enzyme, your body cannot properly break down purines, which are found in many foods and in your own cells. The result is a dangerous buildup of uric acid in your blood and tissues.

Lesch-Nyhan syndrome is inherited in an X-linked pattern, meaning it almost always affects boys. It appears in infancy or early childhood and causes a wide range of physical and neurological problems. Early detection through blood testing can help manage symptoms and prevent serious complications.

• Delayed motor development, trouble sitting or crawling in infancy
• Involuntary muscle movements, muscle spasms, or arching of the back
• Self-injurious behavior, including biting of lips, fingers, or tongue
• Orange-colored sand-like crystals in diapers, a sign of high uric acid
• Kidney stones or bladder stones causing pain or blood in urine
• Gout-like joint pain and swelling, especially in toes and fingers
• Delayed speech and cognitive difficulties
• Irritability, aggression, or other behavioral changes
• Poor muscle control, difficulty with balance and coordination
• Vomiting, poor feeding, or failure to gain weight in infants

Symptoms typically appear between 3 and 12 months of age. Not all symptoms appear at once, but neurological and behavioral signs usually develop early.

Lesch-Nyhan syndrome is caused by mutations in the HPRT1 gene, which provides instructions for making the HGPRT enzyme. This enzyme plays a critical role in recycling purines, the building blocks of DNA and RNA. When the enzyme is missing or not working properly, purines cannot be recycled and are instead converted into uric acid.

The condition is inherited in an X-linked recessive pattern. Mothers carry the mutated gene on one of their X chromosomes but usually do not show symptoms. Male children who inherit the mutated X chromosome will develop the syndrome because they have only one X chromosome. Female carriers have a 50% chance of passing the gene to each child. There are no lifestyle or environmental risk factors, as this is a purely genetic condition present from birth.

Lesch-Nyhan syndrome is diagnosed through a combination of clinical evaluation, blood tests, and genetic testing. Blood tests showing very high uric acid levels are often the first clue. Rite Aid offers uric acid testing as part of our flagship blood panel, which can help detect elevated levels that may indicate this condition.

A definitive diagnosis requires enzyme testing to measure HGPRT activity in red blood cells or genetic testing to identify mutations in the HPRT1 gene. These specialized tests are typically ordered by a geneticist or specialist. Early diagnosis is important for starting treatment that can reduce uric acid levels and prevent kidney damage. If your child shows symptoms or you have a family history of Lesch-Nyhan syndrome, talk to your doctor about testing.

• Medications like allopurinol to lower uric acid production and prevent kidney stones
• Drinking plenty of water to help flush uric acid through the kidneys
• Low-purine diet, avoiding organ meats, certain fish, and alcohol
• Medications to manage muscle spasms and movement disorders
• Behavioral therapy and protective measures to prevent self-injury
• Physical therapy to improve motor skills and coordination
• Regular monitoring of kidney function and uric acid levels
• Pain management for gout symptoms and joint inflammation
• Special education services and developmental support
• Multidisciplinary care team including neurologists, nephrologists, and geneticists