Genetic Clues to Rare Childhood Disorder

Research from the University of California, San Diego School of Medicine provides new clues for the compulsive behavior and cognitive defects associated with a rare childhood neurological disease called Lesch-Nyhan Disease (LND). Two pathways found to be defective in LND are known to be associated with other neurodegenerative disease, such as Alzheimer’s and Parknson’s diseases, suggesting common causes of cognitive and behavioral defects in these neurological disorders.

The research is published on-line today in the PloS ONE.

“This study is important because it opens completely new and unexpected areas of research into the genetic cause of compulsive and self-injurious behavior in Lesch-Nyhan disease,” said principal investigator Theodore Friedmann, MD, professor of pediatrics at UCSD’s Center for Neural Circuit and Behavior and Rady Children’s Hospital-San Diego, a research and teaching affiliate of the UCSD School of Medicine.

“We think that the findings also have implications for far more common diseases related to the central nervous system, such as Alzheimer's and Parkinson’s diseases, since defects similar or related to those that we've found are also seen in other neurodegenerative diseases – suggesting common mechanisms for some of the cognitive, behavioral and neurological defects in all these disorders,” Friedmann added.

LND is an inherited disease caused by a deficiency of the HGPRT enzyme, produced by mutations in the HPRT gene located on the X chromosome, which causes a build-up of uric acid in all bodily fluids. The rare disorder, first identified by medical student Michael Lesch and his mentor, William L. Nyhan – currently a research professor of pediatrics at UC San Diego School of Medicine – is almost always seen in males. Complications usually appear in the first year of life, with neurological signs including poor muscle control and moderate cognitive deficiencies. A particularly disturbing aspect of the disease is uncontrollable and involuntary compulsive self-mutilating behaviors, characterized by lip and finger biting.

What is Lesch-Nyhan syndrome?

Lesch-Nyhan syndrome is a condition characterized by the overproduction and accumulation of uric acid, a waste product of normal chemical processes that is found in blood and urine. The overproduction of uric acid can cause gouty arthritis (arthritis caused by an accumulation of 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, and flailing are often displayed by people affected with this disorder. People with Lesch-Nyhan syndrome usually cannot walk, require assistance sitting, and are generally wheelchair-bound. Self-injury, including biting and head banging, is the most common and distinctive behavioral problem in those with Lesch-Nyhan syndrome.How common is Lesch-Nyhan syndrome?