Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Self-aggression is a behavioural disorder in which an individual damages its own body parts by intense biting or scratching. Self aggression has been reported in human patients in Lesch-Nyhan syndrome and in cases of schizophrenia, depression, and congenital analgesia. In human patients as well as in experimental animals some kind of dysesthesia of the part of the body that is mutilated has been suggested. This study was conducted to find out the underlying pain mechanisms in self-aggressive behaviour arising out of stereotypy. The study was performed in 40 adult male rats. In all these animals, self-aggression was produced as part of amphetamine induced stereotyped behaviour. A predetermined scale was used for quantifying this behaviour. Reserpine and phenoxybenzamine pretreatment led to an increase in the incidence of self-aggression. Naloxone administration in reserpine pretreated animals led to a further significant increase in the incidence of self biting as compared to controls. From these studies it appears that self-aggressive behaviour may be associated with increased pain sensation.
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PMID:Role of opioid receptors in self-aggression in rats. 166 47

A sex-linked familial neurological disease consisting of cerebral palsy, mental retardation, choreoathetosis, and compulsive aggressive behavior is associated with a loss of an enzyme that participates in purine metabolism, namely, hypoxanthine-guanine phosphoribosyltransferase. The production of excessive uric acid in this disorder implies that the enzyme is involved in the normal regulation of purine biosynthesis. This is the first example of a relation between a specific enzyme defect and abnormal compulsive behavior. It is also the first enzyme defect in purine metabolism demonstrated in a neurological disease.
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PMID:Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. 602 Feb 92

This is a report on recent developments in pediatric psychopharmacology: new drugs and new applications for established drugs. The drugs reviewed include imipramine, amitryptiline, lithium, piracetam, propranolol, tryptophan, clonidine, pyridoxine and fenfluramine. Putative indications include prepubertal depression, school phobia, anorexia nervosa, explosive-aggressive behavior, learning disabilities, attention deficit disorder (hyperactivity), Tourette's syndrome, autism, and the Lesch-Nyhan syndrome. Some of the information presented in this report must be regarded as "preliminary," and caution is advised in its interpretation and application.
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PMID:New developments in pediatric psychopharmacology. 635 89

Lesch-Nyhan syndrome is a rare, x-linked, recessive disorder of purine metabolism resulting in hyperuricemia, spasticity, choreoathetosis, dystonia, self-injurious behavior, and aggression, without significant cognitive impairment. Anesthetic management of inpatients who demonstrate classic manifestations of Lesch-Nyhan syndrome and require surgical interventions have been described. There are no guidelines in the literature addressing the anesthetic management of the outpatient with Lesch-Nyhan syndrome. Specifically, sudden, unexplained death, abnormalities in respiration, apnea, severe bradycardia, and an increased incidence of vomiting and chronic pulmonary aspiration may preclude this patient population from receiving anesthesia for outpatient procedures. General anesthesia with spontaneous ventilation was performed for diagnostic, radiographic imaging in 11 outpatients with Lesch-Nyhan syndrome using intravenous propofol. A bolus dose of 1.5 to 2.0 mg/kg propofol was followed by maintenance doses of 60 to 160 mcg/kg/min. Results during and following sedation indicated end-tidal carbon dioxide ranges between 34 mmHg and 59 mmHg. Respiratory rates were never below 10 breaths/min and no partial/complete airway obstruction or labored breathing was clinically evident. Hemodynamics were within 30% of presedation values. No patient demonstrated nausea, vomiting, or pulmonary aspiration. Baseline neuropsychologic status was achieved following sedation, and patients were discharged from the hospital 35 to 90 minutes after sedation was completed. Potential risks and benefits of using propofol in this patient population are discussed.
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PMID:Use of propofol anesthesia during outpatient radiographic imaging studies in patients with Lesch-Nyhan syndrome. 905 48

The Lesch-Nyhan syndrome is an X-linked recessive disorder caused by a deficiency in hypoxanthine-guanine phosphoribosyl transferase, a purine salvage enzyme. Affected individuals exhibit a characteristic neurobehavioral disorder with delayed acquisition of motor skills, dystonia, severe self-mutilations, and aggressive behavior. Deep brain stimulation has been previously proposed for controlling isolated involuntary movements and psychiatric disorders. We applied a double bilateral simultaneous stimulation to limbic and motor internal pallidum in one patient for controlling both behavioral and movement disorders, respectively. The injurious compulsions disappeared; dystonia and dyskinesia were decreased at 28 months follow-up.
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PMID:Antero-ventral internal pallidum stimulation improves behavioral disorders in Lesch-Nyhan disease. 1785 83

Lesch-Nyhan disease (LND) is a severe X-linked neurological disorder caused by a deficiency of hypoxanthine phosphoribosyltransferase (HPRT). In contrast, HPRT-deficiency in the mouse does not result in the profound phenotypes such as self-injurious behavior observed in humans, and the genetic basis for this phenotypic disparity between HPRT-deficient humans and mice is unknown. To test the hypothesis that HPRT deficiency is modified by the presence/absence of phosphoribosyltransferase domain containing 1 (PRTFDC1), a paralog of HPRT that is a functional gene in humans but an inactivated pseudogene in mice, we created transgenic mice that express human PRTFDC1 in wild-type and HPRT-deficient backgrounds. Male mice expressing PRTFDC1 on either genetic background were viable and fertile. However, the presence of PRTFDC1 in the HPRT-deficient, but not wild-type mice, increased aggression as well as sensitivity to a specific amphetamine-induced stereotypy, both of which are reminiscent of the increased aggressive and self-injurious behavior exhibited by patients with LND. These results demonstrate that PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse and could therefore have important implications for unraveling the molecular etiology of LND.
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PMID:PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse. 2181 16