Lesch-Nyhan syndrome

Answer 1

Definition

Lesch-Nyhan syndrome is an inheritable disorder that affects how the body builds and breaks down purines. Purines are a normal part of human tissue and help make up the body's genetic blueprint. They are also found in many different foods.

Causes, incidence, and risk factors

Lesch-Nyhan syndrome is inherited as an X-linked trait. It mostly occurs in boys. Persons with this syndrome are missing or are severely lacking an enzyme called hypoxanthine guanine phosphoribosyltransferase 1 (HGP). The body needs this enzyme to recycle purines. Without it, abnormally high levels of uric acid build up in the body.

The condition affects about 1 in 380,000 people.

Symptoms

The excess uric acid levels cause children to develop gout-like swelling in some of their joints. In some cases, kidney and bladder stones develop because of the high uric acid levels.

Males with Lesch-Nyhan have delayed motor development followed by bizarre, sinuous movements and increased deep tendon reflexes. A striking feature of Lesch-Nyhan syndrome is self-destructive behavior characterized by chewing off fingertips and lips, if not restrained. It is unknown how the enzyme deficiency causes these problems.

Signs and tests

There may be a family history of this condition.

The doctor will perform a physical exam. The exam may show:

• Overexaggerated reflexes
• Spasticity

Blood and urine tests may reveal high uric acid levels. A skin biopsy may show decreased levels of the HGP enzyme.

Treatment

No specific treatment exists for Lesch-Nyhan syndrome. The gout medication, allopurinol, successfully decreases uric acid levels, but does not improve the neurological outcome.

Some symptoms may be relieved with the drugs carbidopa/levodopa, diazepam, phenobarbital, or haloperidol.

Expectations (prognosis)

The outcome is likely to be poor. Persons with this syndrome usually require assistance walking and sitting and generally need a wheelchair to get around.

Complications

Severe, progressive disability is likely.

Calling your health care provider

Call your health care provider if signs of this illness appear in your child or if there is a history of Lesch-Nyhan syndrome in your family.

Prevention

Genetic counseling for prospective parents with a family history of Lesch-Nyhan syndrome is recommended. Testing can be done to see if a woman is a carrier of this syndrome.

References

Harris JC. Disorders of purine and pyrimidine metabolism. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 89.

Answer 2

Definition

Lesch-Nyhan syndrome is an inheritable disorder that affects how the body builds and breaks down purines. Purines are a normal part of human tissue and help make up the body's genetic blueprint. They are also found in many different foods.

Causes, incidence, and risk factors

Lesch-Nyhan syndrome is inherited as an X-linked trait. It mostly occurs in boys. Persons with this syndrome are missing or are severely lacking an enzyme called hypoxanthine guanine phosphoribosyltransferase 1 (HGP). The body needs this enzyme to recycle purines. Without it, abnormally high levels of uric acid build up in the body.

The condition affects about 1 in 380,000 people.

Symptoms

The excess uric acid levels cause children to develop gout-like swelling in some of their joints. In some cases, kidney and bladder stones develop because of the high uric acid levels.

Males with Lesch-Nyhan have delayed motor development followed by bizarre, sinuous movements and increased deep tendon reflexes. A striking feature of Lesch-Nyhan syndrome is self-destructive behavior characterized by chewing off fingertips and lips, if not restrained. It is unknown how the enzyme deficiency causes these problems.

Signs and tests

There may be a family history of this condition.

The doctor will perform a physical exam. The exam may show:

• Overexaggerated reflexes
• Spasticity

Blood and urine tests may reveal high uric acid levels. A skin biopsy may show decreased levels of the HGP enzyme.

Treatment

No specific treatment exists for Lesch-Nyhan syndrome. The gout medication, allopurinol, successfully decreases uric acid levels, but does not improve the neurological outcome.

Some symptoms may be relieved with the drugs carbidopa/levodopa, diazepam, phenobarbital, or haloperidol.

Expectations (prognosis)

The outcome is likely to be poor. Persons with this syndrome usually require assistance walking and sitting and generally need a wheelchair to get around.

Complications

Severe, progressive disability is likely.

Calling your health care provider

Call your health care provider if signs of this illness appear in your child or if there is a history of Lesch-Nyhan syndrome in your family.

Prevention

Genetic counseling for prospective parents with a family history of Lesch-Nyhan syndrome is recommended. Testing can be done to see if a woman is a carrier of this syndrome.

References

Harris JC. Disorders of purine and pyrimidine metabolism. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 89.

Reviewed By

Review Date: 04/26/2010

Neil K. Kaneshiro, MD, MHA, Clinical Assistant Professor of Pediatrics, University of Washington School of Medicine. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.