COMPASSIONATE ALLOWANCE INFORMATION

Hereditary Hyperuricemia and Choreoathetosis Syndrome; Hyperuricemia Choreoathetosis-Self mutilation Syndrome; Hyperuricemia-Oligophrenia; Hypoxanthine-Guanine Phosphoribosyltranferase Deficiency (HGPRT); Hypoxanthine phosphoribosyltransferase Deficiency (HPRT); Juvenile Gout-Choreoathetosis and Intellectual Disability Syndrome; Lesch Nyhan Disease; Nylan Syndrome

Lesch-Nyhan syndrome (LNS) is a rare, inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). LNS is an X-linked recessive disease-- the gene is carried by the mother and passed on to her son. LNS is present at birth in baby boys (females are carriers of the gene). The lack of HPRT causes a build-up of uric acid in all body fluids, and leads to severe gout, poor muscle control, and moderate intellectual disability, which appear in the first year of life. Hypotonia and delayed motor milestones are usually evident by three to six months of age. The motor disability is so severe that virtually all children with LNS never walk and are confined to a wheelchair. Neurological signs include facial grimacing, involuntary writhing, and repetitive movements of the arms and legs similar to those seen in Huntington's disease. A striking feature of LNS is self-mutilating behaviors - characterized by lip and finger biting - that begin in the second year of life. Because a lack of HPRT causes the body to poorly utilize vitamin B12, some boys may develop a rare disorder called megaloblastic anemia.

Diagnostic testing: Molecular genetic testing is the most effective method of testing, as HPRT1 is the only gene known to be associated with LNS. Individuals who display the full Lesch-Nyhan phenotype all have mutations in the HPRT1 gene. Some consider the definitive confirmatory test to be the results of HPRT enzyme activity of less than 1.5% of normal blood or other type tissue cells.

The prognosis for individuals with LNS is poor. Death usually occurs in the first or second decade of life.

Treatment for LNS is symptomatic. Gout can be treated with allopurinol to control excessive amounts of uric acid. Kidney stones may be treated with lithotripsy, a technique for breaking up kidney stones using shock waves or laser beams. There is no standard treatment for the neurological symptoms of LNS. Some may be relieved with the drugs carbidopa/levodopa, diazepam, phenobarbital, or haloperidol.

REMARKS