Lesch-Nyhan syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at January 4, 2017
StartDiseasesLesch-Nyhan syndrome

Lesch-Nyhan syndrome is a genetic disorder that affects males almost exclusively. It causes abnormal behavioral patterns and neurological changes and involves a buildup of uric acid. The collection of this chemical waste is collected beneath the skin. This condition impairs the functioning of the neuromuscular system and causes stones in the kidneys and bladder. People with Lesch-Nyhan syndrome typically cannot walk and use wheelchairs.


Definition & Facts

Lesch-Nyhan syndrome occurs mostly in men due to a genetic mutation in their X chromosome, meaning it is passed along from the birth mother to the son. In those affected, the hypoxanthine phosphoribosyltransferase gene (HPRT gene) has defects which result in the abnormal or deficient production of HPRT, an enzyme that helps recycle purines. The lack of the enzyme causes a buildup of uric acid that would normally be filtered through blood and urine.

Found in one out of every 380,000 people, Lesch-Nyhan syndrome can typically be detected before the a patient's first birthday. By the age of two, the more dramatic signs of the syndrome can hardly be ignored. Gout, anemia, kidney problems, and bladder complications are the more clear signs of being affected by this condition. Patients may exhibit behaviors of self-injury early on in life.

Symptoms & Complaints

When collected near joints and pooling just beneath the skin, uric acid can lead to gout, causing arthritic symptoms such as joint swelling and tenderness.

Inability to reach developmental milestones is common among those with Lesch-Nyhan syndrome. As the child grows older, the first few years may see an increase in irritability. Dystonia, muscle spasms, and chorea are symptoms as well.

These are neurological responses that are eventually accompanied by self-harming behavior, something that affects an approximate 85 percent of those with this condition. This can be anything as slight as biting of the fingers or lips to as damaging as banging the head against hard surfaces. All these symptoms can be reasonably expected to increase as the affected ages.


Most with Lesch-Nyhan syndrome, typically male, inherit the condition from the mother. This X-linked trait prohibits the proper filtration of purines, causing the buildup of uric acid.

A female genetic carrier has a 50 percent chance to pass it along during a pregnancy to either a son or daughter, meaning the latter would develop this condition and the former would be a carrier with equal chances to give it to their offspring. The same carrier also has a 50 percent chance of having a healthy birth of an child of either sex.

In addition to its effect on the buildup of uric acid, the decline in the HPRT is associated with problems with dopamine though the exact mechanisms for the HPRT deficiency leads to neurological symptoms associated are not directly known.

Diagnosis & Tests

An intake of the patient's medical history, family history, and symptom presentation will occur. A physical examination will be performed. Blood tests, clinical urine tests, genetic testing, and skin biopsies may all be used to detect the abnormalities associated with this condition. Urine and blood tests can show the build up of uric acid. Neurological evaluations and examinations can test reflexes and reveal difficulty controlling movement. Psychological and behavioral evaluations can examine a person's behavior for self-injury.

Treatment & Therapy

Lesch-Nyhan syndrome is a complex condition that is treated through managing its symptoms. Kidney stones and bladder stones, arthritic pain, and gout can be treated through a combination of medication and surgical procedures. Cystolithotomy and cystolitholapaxy are procedures used to remove bladder stones. Nephrolithotomy is a procedure which removes kidney stones. Diazepam, phenobarbital, and haloperidol may be diagnosed to improve some of the neurological symptoms of this disorder.

Prevention & Prophylaxis

Because this is a genetic disorder, it cannot be prevented. Those who are aware of their status as a carrier of a defective HPRT gene, and those who are considering children may choose to undergo genetic counseling in order to assess the risk that their children could inherit this condition.