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behavioral aspects of lesch–nyhan disease and its variants
- david j schretlen, julianna ward, stephen m meyer, jonathan yun, juan g puig, william l nyhan, ha jinnah, james c harris
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- Journal:
- Developmental Medicine and Child Neurology / Volume 47 / Issue 10 / October 2005
- Published online by Cambridge University Press:
- 12 September 2005, pp. 673-677
- Print publication:
- October 2005
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- Article
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self-injury is a defining feature of lesch–nyhan disease (lnd) but does not occur in the less severely affected lesch–nyhan variants (lnv). the aim of this study was to quantify behavioral and emotional abnormalities in lnd and lnv. thirty-nine informants rated 22 patients with lnd (21 males, 1 female), 11 males with lnv, and 11 healthy controls (hc; 10 males, 1 female) using two well-validated rating scales. the age of patients with lnd ranged from 12 years 7 months to 38 years 3 months (mean 22y 11mo; sd 7y 8mo), whereas the age range of those with lnv was 12 years 9 months to 65 years (mean 30y 7mo; sd 15y 2mo), and the healthy controls were aged 12 years 4 months to 31 years 3 months (mean 17y 10mo; sd 5y 7mo). behavioral ratings were based on the child behavior checklist and the american association on mental retardation's adaptive behavior scale – residential and community, 2nd edition. statistical analyses revealed that patients with lnd showed severe self-injury together with problematic aggression, anxious-depressed symptoms, distractibility, motor stereotypes, and disturbing interpersonal behaviors. patients with lnv were rated as being intermediate between the hc and lnd groups on all behavior scales. although the lnv group did not differ from hcs on most scales, their reported attention problems were as severe as those found in lnd. we conclude that self-injurious and aggressive behaviors are nearly universal and that other behavioral abnormalities are common in lnd. although patients with lnv typically do not self-injure or display severe aggression, attention problems are common and a few patients demonstrate other behavioral anomalies.
24 - Lesch–Nyhan syndrome
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- By William L. Nyhan, Department of Pediatrics and Institute for Molecular Genetics, University of California San Diego, La Jolla, California, USA
- Edited by E. Steve Roach, Wake Forest University, North Carolina, Van S. Miller, University of Texas Southwestern Medical Center, Dallas
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- Book:
- Neurocutaneous Disorders
- Published online:
- 31 July 2009
- Print publication:
- 08 January 2004, pp 186-199
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Summary
Introduction
Lesch–Nyhan disease, the most common and most thoroughly studied of the disorders of purine metabolism, was first described as a syndrome in 1964 (Lesch & Nyhan, 1964). The initial two patients were brothers, an early indication of the X-linked recessive nature of the disease, which shortly became evident with the study of the pedigrees of families with numbers of affected males (Nyhan et al., 1967). The older brother of the proband was in an institution with a diagnosis of mental retardation and cerebral palsy, when the younger brother was admitted with hematuria and found to have hyperuricemia and uricosuria and had bizarre and compulsive, self-mutilative biting. Both brothers exhibited involuntary choreoathetoid movements. A hallmark feature of the disease has continued to be loss of tissue resulting from biting or some other form of self-injurious behavior. Biochemical studies identified that the uric acid pool was enlarged and its turnover was abnormally rapid. The overproduction of purine from an intravenous glycine precursor was 20 times the normal value (Nyhan, 1968), whereas in adults with gouty arthritis the greatest rates of de novo synthesis of purines observed were twice the normal value.
The molecular defect is the virtually complete absence of activity of the enzyme hypoxanthine guanine phosphoribosyl transferase (HPRT) (Fig. 24.1) (Seegmiller et al., 1967). HPRT catalyzes the reaction in which the purine bases, hypoxanthine and guanine, are converted in what has been referred to as a salvage or reutilization pathway to their respective nucleotides, inosinic acid (IMP) and guanylic acid (GMP).