Lesch-Nyhan Syndrome

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What is Lesch-Nyhan syndrome?

Lesch-Nyhan syndrome is a condition characterized by the overproduction of uric acid, a nitrogen-containing compound found in blood and urine. The overproduction of uric acid can cause gouty arthritis (arthritis caused by uric acid in the joints), kidney stones, and bladder stones. Problems with the nervous system and behavioral disturbances are also characteristic of this disorder. Abnormal involuntary muscle movements such as flexing, jerking, flinging, and flailing are often displayed by people affected with this disorder. Self-injury, including biting and head banging, is the most common and distinctive behavioral problem in Lesch-Nyhan patients.

How common is Lesch-Nyhan syndrome?

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

What genes are related to Lesch-Nyhan syndrome?

Mutations in the HPRT1 gene cause Lesch-Nyhan syndrome.

Mutations in the HPRT1 gene cause a severe deficiency of the enzyme hypoxanthine phosphoribosyltransferase 1. This enzyme is responsible for recycling purines, a type of building block for DNA and its chemical cousin RNA. When this enzyme is lacking, the breakdown of purines results in abnormal levels of uric acid in the body. It is unclear how a shortage of this enzyme causes the neurological and behavioral problems characteristic of Lesch-Nyhan syndrome.

How do people inherit Lesch-Nyhan syndrome?

This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome (one of the two sex chromosomes). In males, who have only one X chromosome, one altered copy of the gene is sufficient to cause the condition. In females, who have two X chromosomes, a mutation must usually be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Source: National Institutes of Health

Study results from La Paz University, Division of Clinical Biochemistry broaden understanding of metabolism

"The aim of the study was to analyze the long-term efficacy and safety of allopurinol in patients with HPRT deficiency. Nineteen patients (13 with Lesch-Nyhan syndrome and 6 with partial HPRT deficiency) were treated with allopurinol (mean dose, 6.4 mg/kg body weight per day; range, 3.7-9.7 mg/kg body weight per day) and followed up for at least 12 months (mean follow-up, 7.6 years). The efficacy of allopurinol was evaluated by serial measurement of purine metabolic parameters and renal function as well as by clinical manifestations. Safety was assessed by recording adverse events. Treatment with allopurinol normalized serum urate level in all patients and resulted in a mean reduction in serum urate of 47%. Allopurinol treatment was associated with a mean 74% reduction in urinary uric acid-to-creatinine ratio. In contrast, allopurinol treatment increased mean hypoxanthine and xanthine urinary excretion rates 5.4-and 9.5-fold, respectively, compared with baseline levels. The decrease in uric acid excretion in complete and partial HPRT-deficient patients was not accompanied by a stoichiometric substitution of hypoxanthine and xanthine excretion rates. Allopurinol-related biochemical changes were similar in patients with either complete or partial HPRT deficiency. Renal function remained stable or improved with treatment. Three patients had urolithiasis during allopurinol treatment. In 2 patients, xanthine stones were documented and they required allopurinol dose adjustments aimed at reducing excessive oxypurine excretion rates. No allopurinol hypersensitivity reactions occurred. Neurologic manifestations were not influenced by allopurinol therapy," wrote R.J. Torres and colleagues, La Paz University, Division of Clinical Biochemistry.

The researchers concluded: "Allopurinol is efficacious and generally safe for the treatment of uric acid overproduction in patients with HPRT deficiencies. Xanthine lithiasis, developing as a consequence of allopurinol therapy, should be preventable by adjustment of allopurinol dose.'."

Torres and colleagues published their study in Metabolism (Efficacy and safety of allopurinol in patients with hypoxanthine-guanine phosphoribosyltransferase deficiency. Metabolism, 2007;56(9):1179-86).

For additional information, contact R.J. Torres, La Paz University Hospital, Division of Clinical Biochemistry, Madrid, Spain.

Publisher contact information for the journal Metabolism is: W B Saunders Co., Independence Square West Curtis Center, Ste. 300, Philadelphia, PA 19106-3399, USA.

Keywords: Spain, Madrid, Allopurinol, Drugs, Enzyme Research, Metabolism, Pharmaceuticals, Phosphoribosyltransferase, Therapy, Treatment, Wellness.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.