Diagnosis and treatmen t of th e leschnyhan syndrome 505 sigmoidal kinetics with ppribosep as the variable substrate fig. Lesch nyhan syndrome is a condition characterized by neurological. Five boys with leschnyhan syndrome and varying degrees of dystonia, chorea, spasticity, ataxia, dysarthria, and mental retardation were studied at the depts of neurology and medicine, baylor. It is characterized by neurological and behavioral abnormalities and the overproduction of uric acid. Leschnyhan syndrome genes and disease ncbi bookshelf. An overview of leschnyhan syndrome abstract leschnyhan syndrome is a disorder that strikes the sufferer with debilitating motor and cognitive problems, hyperuricemia, and the urge to do harm to yourself with acts of selfinjurious behavior.
Leschnyhan syndrome is a rare disorder that affects males. Research has lead to the discovery of a genetic sequence that results in a defective enzyme, but. Leschnyhan disease lnd is a neurodevelopmental disorder with a characteristic neurobehavioral syndrome with behavioral, cognitive and motor components that include selfinjurious behavior sib, cognitive disability of varying degree, and severe generalized dystonia. Lesch nyhan syndrome lns was first described at john hopkins hospital in 1964 fig. Leschnyhan syndrome lns or kelleyseegmiller syndrome is a rare hereditary disorder that affects the bodys ability to breakdown and build purines. Leschnyhan disease lnd is a rare inherited disorder caused by mutations in the gene encoding hypoxanthineguanine phosphoribosyltransferase hprt. Schematic illustration of the crosstalk between the unfolded protein response upr, mitochondria, autophagy, and inflammatory and cell death pathways.
It is observed in males and is present since birth. Leschnyhan syndrome is a condition that occurs almost exclusively in males. Leschnyhan syndrome is a metabolic disorder of purine and pyrimidine metabolism. Leschnyhan syndrome is inherited in an xlinked manner. Leschnyhan syndrome an overview sciencedirect topics. Selfmutilation in the leschnyhan syndrome neurology. Control spinal fluids for agematched comparison were obtained from 194 neurologic and nonneurologic pediatric patients. Hypoxanthineguanine phosophoribosyltransferase hprt. If you have problems viewing pdf files, download the latest version of adobe reader. The cause of the syndrome is a defective organic catalyst or enzyme. Lnd is characterized by overproduction of uric acid, leading to gouty arthritis and nephrolithiasis. The invitae leschnyhan syndrome test analyzes the hprt1 gene, which is associated with leschnyhan syndrome, a disorder with a phenotypic spectrum ranging from neurological dysfunction, cognitive impairment and behavioural disturbances in affected males at the severe end of the spectrum to isolated hyperuricemia and gout at the mild end of the. Lesch nyhan syndrome or lns is a rare disorder, which runs in families. Lesch nyhan syndrome is inherited in an xlinked manner.
A familial disorder of uric acid metabolism and central nervous system function. Leschnyhan syndrome lns is a rare xlinked disorder caused by mutations in hprt1, an important enzyme in the purine salvage pathway. Lesch nyhan syndrome lns is a rare xlinked disorder of purine metabolism associated with hyperuricemia and caused by absence or near complete absence of the enzyme hypoxanthine guanine phosphoriboxyl transferase hgprt, essential for purine salvage nyhan 2004, seegmiller et al. Serial determinations of spinal fluid homovanillic acid hva and 5hydroxyindoleacetic acid 5hiaa were made in four patients with the leschnyhan syndrome over a 5year period. The disorder was first recognized and clinically characterized by american medical student michael lesch and his.
Medical definition of leschnyhan syndrome merriamwebster. Patients with leschnyhan syndrome should be carefully evaluated in the preoperative period especially to. Leschnyhan syndrome lns was first described at john hopkins hospital in 1964 fig. Lesch nyhan syndrome childrens research foundation.
An overview of leschnyhan syndrome rutgers university. Leschnyhan syndrome information page national institute. Case report management and prevention of oral self. Anesthetic management of leschnyhan syndrome case report. The risk to sibs of a proband depends on the carrier status of the mother. Lns is an xlinked recessive disease the gene is carried by the mother and passed on to her son. Haj has served on the scientific advisory boards for the leschnyhan syndrome childrens research foundation in the us and for leschnyhan action in france. It almost always occurs in boys and is due to a build up of uric acid in the body. Effective management of this problem requires three ingredients. He has received grant support from the nih, the leschnyhan syndrome childrens research foundation, and psyadon pharmaceuticals for research on leschnyhan disease. Attempts to explain the pathogenesis of neuropsychiatric disorders are frustrated by the fragmentary information available relating neurochemistry to brain function. If left untreated, it can produce nephrolithiasis with renal failure, gouty arthritis, and solid subcutaneous deposits known as tophi. The term leschnyhan variants has been introduced to include patients with hprtrelated gout and some degree of neurological involvement, but without the complete leschnyhan syndrome.
The behavior problems, including selfinjurious behavior, can also be difficult to eliminate. The abnormally increased uric acid levels can further lead to other. More than 210 hprt1 mutations are associated with leschnyhan syndrome, and its severity correlates with the severity of the genetic lesion. Affected patients also have characteristic neurological and behavioral anomalies. If a male is suspected to be affected with leschnyhan syndrome lns, enzyme testing and genetic testing are both available. 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. Since it is an xlinked disease it is found almost exclusively in males although affected manifesting females have been identified albeit very rarely. Leschnyhan syndrome is inherited as an xlinked recessive disorder with an incidence of approximately 1. Purines are a normal part of human tissue that help make up the bodys genetic blueprint. A purine adenine, guanine is a protein found in normal healthy body tissue that makes the bodys blueprint. It is an xlinked deficiency of the enzyme hypoxanthineguanine phosphoribosyltransferase hprt, encoded by the hprt1 gene.
Leschnyhan syndrome lns, a rare inborn error of metabolism, is characterized by selfinjurious behavior, which results in partial or total. Deutsche medicinische wochenschrift, stuttgart, 1959, 84. This deficiency occurs due to mutations in the hprt1 gene located on the x chromosome. Sometimes an initial screen to check the uric acid levels in the blood or urine is performed. The leschnyhan syndrome results from deficient hypoxanthineguanine phosphoribosyltransferase activity. Attention is paid to the leschnyhan syndrome and tourettes syndrome as examples of clinical syndromes that are particularly associated with sib.
Lesch nyhan syndrome an overview sciencedirect topics. Leschnyhan syndrome, hereditary metabolic disorder affecting the central nervous system and characterized by incoordination, mental retardation, aggressive behaviour, and compulsive biting. The overproduction of uric acid is associated with hyperuricemia. Leschnyhan disease symptoms, diagnosis and treatment. Lesch nyhan syndrome nord national organization for. Without the enzyme being present it can lead to buildup of uric acid in the person body that will affect the nervous system, the kidneys and other. It is transmitted as an xlinked excessive character in which the primary expression of the mutant gene is in the activity of the enzyme hypoxanthine guanine phosphoribosyltransferase hgprt.
Clinical features include hyperuricemia, developmental delay, movement disorders, and selfmutilation targeted to the lips, tongue, and digits. These raw materials are called purines, and they are an essential part of dna and rna. The leschnyhan syndrome american journal of psychiatry. The clinical picture of the classic form of leschnyhan disease usually includes three things. Utilization of purines by an hprt variant in an intelligent, nonmutilative patient with features of the lesch nyhan syndrome. According to one estimate, the disorder occurs at the rate of approximately one in 380,000 births in the united states. Uric acid is a waste product of normal chemical processes of the body and is found in blood and urine. Five boys with lesch nyhan syndrome and varying degrees of dystonia, chorea, spasticity, ataxia, dysarthria, and mental retardation were studied at the depts of neurology and medicine, baylor. Typical symptoms include the tendency of compulsions to selfmutilate. Both brothers presented severe retardation of motor development, choreoathetosis, dystonia, crystals in the urine later determined to be composed of uric acid, and. Leschnyhan syndrome is caused by gene mutation where there is an absence of the enzyme hprt1 hypoxanthineguanine phosphoribosyl transferase 1 that will metabolize uric acid and produce purines. Leschnyhan syndrome lns is a rare xlinked recessive disorder with an incidence of 1100,000380,000 live births. Also known as nyhans syndrome, kelley seegmiller syndrome and juvenile goutit is a hereditary disorder of purine metabolism, characterized by menntal retardation, selfmutilation of the fingers and lips by biting, impaired renal function, and abnormal physical development. Leschnyhan syndrome is a condition that causes neurological problems that resemble cerebral palsy and characteristic behavioral issues.
For language access assistance, contact the ncats public information officer. Leschnyhan disease is a genetic disorder associated with 3 major clinical elements. The father of an affected male will neither have the disease nor be a carrier of the mutated allele. Here we report our anesthesia experience in a 4 yearsold child with leschnyhan syndrome, who underwent cataract surgery. Pdf leschnyhan syndrome, a rare inborn error of metabolism, is characterized by mental retardation and selfdestructive behavior resulting in. The disorder is characterized by increased production of uric acid, which is normally found in blood and urine and some neurological and behavioral abnormalities. Neurotransmitters and the leschnyhan syndrome nejm. If there is uric acid overproduction hyperuricemia, this is. Leschnyhan syndrome is characterized clinically by mental retardation, choreoathetosis, spastic cerebral palsy, and aggressive, selfmutilating behavior.