Lesch-Nyhan syndrome is a rare inborn error of metabolism. It occurs due to an issue with an enzyme, resulting in an overproduction of uric acid in the body.

Inborn errors of metabolism are a group of conditions that affect metabolic pathways. These are the chemical processes that allow the body to turn food into energy. When part of this process is unable to function correctly, it can result in the buildup of harmful substances in the body.

Dr. Michael Lesch and Dr. William Nyhan discovered the condition in the mid-1960s after identifying two brothers with high levels of uric acid in their blood. The condition occurs due to issues with the enzyme known as hypoxanthine-guanine phosphoribosyltransferase (HPRT), which results in the accumulation of uric acid.

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Sex and gender exist on spectrums. This article will use the terms “male,” “female,” or both to refer to sex assigned at birth. Click here to learn more.

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Lesch-Nyhan syndrome is a rare, inherited condition that almost exclusively affects males. It occurs due to the absence or deficiency of an enzyme, resulting in the overproduction and accumulation of uric acid in the body. This buildup of uric acid can manifest as various neurological and behavioral issues.

Other names for the condition include:

  • Lesch-Nyhan disease
  • hypoxanthine-guanine phosphoribosyl transferase deficiency
  • HGPRT deficiency
  • HPRT deficiency

Lesch-Nyhan syndrome is an X-linked recessive condition. This means that the genetic variation that causes the condition is present on the X chromosome. The female parent will typically carry the genetic alteration and pass it on to male offspring.

This is because males usually have only one copy of the X chromosome, which they inherit from the female parent. As such, if a male inherits an X chromosome with the variation, they will develop the disease. However, while it is very rare, it is also possible for a female to have the condition.

The HPRT gene

The gene on the X chromosome related to Lesch-Nyhan syndrome is HPRT1. This gene is responsible for producing the enzyme HPRT. An alteration in the HPRT1 gene can result in the absence or deficiency of the HPRT enzymes, which may lead to high levels of uric acid.

The HPRT enzyme plays an important role in the purine salvage pathway. This important metabolic pathway recycles the building blocks of RNA and DNA. The HPRT enzymes help break down purines, which are present in foods such as meats and legumes.

Without a functioning HPRT enzyme to help this chemical process, purines can turn into uric acid. This accumulation of uric acid can then manifest as the clinical symptoms of Lesch-Nyhan syndrome.


Evidence suggests that Lesch-Nyhan syndrome occurs in roughly 1 in every 100,000–380,000 live births. With each pregnancy, female carriers of the condition have:

  • a 25% chance of a carrier female
  • a 25% chance of a noncarrier female
  • a 25% chance of an affected male
  • a 25% chance of an unaffected male

If a male with the condition is able to reproduce, they will pass the gene variation to all female offspring. However, they cannot pass the alteration onto male children, as they instead inherit the Y chromosome from their male parent.

The symptoms of Lesch-Nyhan syndrome occur due to a buildup of uric acid in body fluids. In some cases, the uric acid can also cause sodium urate crystals to form in the body.

Some symptoms of Lesch-Nyhan syndrome may become apparent at 6 months of age, while others may develop later. Symptoms may include:

  • urate crystals, or orange sand, present in urine
  • impaired kidney function due to kidney stones
  • blood in the urine
  • gout-like painful and swollen joints
  • facial grimacing
  • jerking movements
  • involuntary movements
  • reduced muscle tension, although some may later experience increased muscle tone
  • muscle spasms, known as opisthotonos, may cause the back to arch severely and the head and heels to bend backward
  • overactive bodily reflexes
  • difficulty swallowing
  • issues with articulation
  • low weight for age
  • self-injury behaviors, such as lip and finger biting, banging their head against hard objects, and scratching their face
  • other behavioral issues, such as aggression, irritability, spitting, and screaming
  • intellectual disability
  • developmental delay with milestones such as crawling, sitting, or walking

Low levels of HPRT can also cause the body to use vitamin B12 less effectively. As such, some people may develop megaloblastic anemia. This is a condition that causes large red blood cells. As a result, the body is unable to deliver sufficient oxygen to tissues and organs, which can cause fatigue and shortness of breath.

Female carriers of Lesch-Nyhan often do not have symptoms. However, they may later develop gout due to hyperuricemia (excess uric acid in the blood).

Diagnosis of Lesch-Nyhan syndrome will typically involve a combination of a detailed medical history, physical examination, and blood tests to detect high levels of uric acid.

Where available, a doctor can also perform further tests to identify a gene variation in HPRT1, and the absence of the HPRT enzyme in cells from any tissue can confirm the diagnosis.

Sometimes, such as if there is a known family history of Lesch-Nyhan syndrome, prenatal diagnosis may also be possible.

Treatment options for Lesch-Nyhan syndrome will typically depend on the individual’s specific symptoms. Often, treatment may require a multidisciplinary team that may include pediatricians, orthopedists, and physical therapists.

To help manage gout, a doctor may prescribe allopurinol. This is a medication that can help reduce levels of uric acid in the blood. For kidney stones, a medical professional may recommend extracorporeal shock wave lithotripsy. This method can break up kidney stones by using high energy sound waves to allow a person to pass the fragments when urinating.

There are currently no standard treatments for the neurological and musculoskeletal symptoms of Lesch-Nyhan syndrome. However, a doctor may recommend the following medications:

While success varies, some people may also benefit from behavior modification techniques to help reduce self-injury behaviors. Other times, people may require physical restraints, mouth guards, and dental extractions.

Lesch-Nyhan syndrome is an inherited inborn error of metabolism. It occurs due to a problem with the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). The condition predominantly affects males as it is an X-linked recessive condition.

The HPRT enzyme plays an important role in the purine salvage pathway. When this enzyme does not function correctly, it causes excessive levels of uric acid to accumulate. The high levels of uric acid in the blood causes kidney, neurological, and behavioral problems. This can include impaired kidney function, intellectual disability, and behaviors that cause self-injury.

Treatment will depend on the symptoms. It may involve a combination of medication, physical restraints, and behavioral therapy.