Lesch Nyhan syndrome

Other Names: LNS; HPRT deficiency, complete; Lesch-Nyhan syndrome; Lesch Nyhan disease; Choreoathetosis self-mutilation syndrome; Complete HPRT deficiency complete; Hypoxanthine-guanine phosphoribosyltransferase deficiency

Lesch Nyhan syndrome is a condition characterized by neurological and behavioral abnormalities and the overproduction of uric acid in the body. It occurs almost exclusively in males. Uric acid is a waste product of normal chemical processes and is found in blood and urine. Excess uric acid can be released from the blood and build up under the skin and cause gouty arthritis (arthritis caused by an accumulation of uric acid in the joints). Uric acid accumulation can also cause kidney and bladder stones.

Epidemiology

The prevalence of Lesch-Nyhan syndrome is approximately 1 in 380,000 individuals. This condition occurs with a similar frequency in all populations.

Cause

Mutations in the HPRT1 gene cause Lesch-Nyhan syndrome. The HPRT1 gene provides instructions for making an enzyme called hypoxanthine phosphoribosyltransferase 1. This enzyme is responsible for recycling purines, a type of building block of DNA and its chemical cousin RNA. Recycling purines ensures that cells have a plentiful supply of building blocks for the production of DNA and RNA.

HPRT1 gene mutations that cause Lesch-Nyhan syndrome result in a severe shortage (deficiency) or complete absence of hypoxanthine phosphoribosyltransferase 1. When this enzyme is lacking, purines are broken down but not recycled, producing abnormally high levels of uric acid. For unknown reasons, a deficiency of hypoxanthine phosphoribosyltransferase 1 is associated with low levels of a chemical messenger in the brain called dopamine. Dopamine transmits messages that help the brain control physical movement and emotional behavior, and its shortage may play a role in the movement problems and other features of this disorder. However, it is unclear how a shortage of hypoxanthine phosphoribosyltransferase 1 causes the neurological and behavioral problems characteristic of Lesch-Nyhan syndrome.

Some people with HPRT1 gene mutations produce some functional enzyme. These individuals are said to have Lesch-Nyhan variant. The signs and symptoms of Lesch-Nyhan variant are often milder than those of Lesch-Nyhan syndrome and do not include self-injury.

Inheritance

X-linked recessive inheritance

This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Signs and symptoms

Signs and symptoms may include inflammatory arthritis (gout), kidney stones, bladder stones, and moderate cognitive disability. Nervous system and behavioral disturbances also occur, such as involuntary muscle movements and self injury (including biting and head banging). People with Lesch Nyhan syndrome usually cannot walk, require assistance sitting, and generally use a wheelchair. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Abnormality of movement(Movement disorder)
• Behavioral abnormality(Behavioral changes)
• Gout
• Hemiplegia/hemiparesis(Paralysis or weakness of one side of body)
• Hyperuricemia(High blood uric acidlevel)
• Intellectual disability, mild(Mental retardation, borderline-mild)
• Intellectual disability, moderate(IQ between 34 and 49)
• Spasticity(Involuntary muscle stiffness, contraction, or spasm)

30%-79% of people have these symptoms

• Anemia(Low number of red blood cells or hemoglobin)
• Hematuria(Blood in urine)
• Renal insufficiency(Renal failure)

Diagnosis

There may be a family history of this condition. The health care provider will perform a physical exam. The exam may show:

• Increased reflexes
• Spasticity (having spasms)
• Blood and urine tests may show high uric acid levels. A skin biopsy may show decreased levels of the HPRT1 enzyme.

Treatment

No specific treatment exists for Lesch-Nyhan syndrome. Medicine for treating gout can lower uric acid levels. However, treatment does not improve the nervous system outcome (for example, having increased reflexes and spasms).

Some symptoms may be relieved with these medicines:

• Carbidopa/levodopa
• Diazepam
• Phenobarbital
• Haloperidol
• Self-harm can be reduced by removal of teeth or by using a protective mouth guard designed by a dentist.

You can help a person with this syndrome using stress-reduction and positive behavioral techniques.

Prognosis

The outcome is likely to be poor. People with this syndrome usually need help walking and sitting. Most need a wheelchair. Possible Complications Severe, progressive disability is likely.

NIH genetic and rare disease info

• NIH info on Lesch Nyhan syndrome

Lesch Nyhan syndrome is a rare disease.

Lesch Nyhan syndrome Resources
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