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)

The Lesch-Nyhan syndrome is a rare inborn error of purine metabolism associated with hyperuricacidemia, mental retardation, and an insatiable urge for self-mutilation, especially of the extremities. Insensitivity to pain and severe muscle spasms create very difficult management problems, especially for children being cared for at home. Fortunately this syndrome is rare (1 per 380,000 live births). Four known patients are under treatment in Manitoba, of which two brothers are the subject of this study. In general, the medical management of these patients has been unsuccessful, especially in controlling self-mutilation. It therefore was decided to manage these children by the use of mechanical aids. Through the utilization of custom-designed seating devices control of the self-mutilation has been obtained, reducing the burden of family care. It is now possible for the children to attend regular school on a half-day basis. They are also able to engage in community activities without the fear that a mishap will occur when not under the vigilance of the immediate family.
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PMID:Special devices as aids in the management of child self-mutilation in the Lesch-Nyhan syndrome. 113 85

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

The spectrum of orthopaedic problems in eight congenitally insensate patients was reviewed. The conditions included congenital insensitivity to pain, Riley-Day syndrome, and Lesch-Nyhan syndrome. In each of these conditions, the patient has an abnormality of interpretation of painful stimuli or lacks normal pain avoidance, leading to self-inflicted damage. The orthopaedic problems and complications included fracture, self-mutilation, autoamputation, osteomyelitis, septic arthritis, Charcot joints, scoliosis, and dislocation. Effective management consists of early diagnosis and patient/parent education to prevent as many complications as possible. Fractures may be treated conservatively, while progressive scoliosis requires operative intervention. Osteomyelitis, septic arthritis, and Charcot joints require appropriate operative treatment.
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PMID:Orthopaedic manifestations in congenitally insensate patients. 169 84

A 15-year-old male with a long history of self-mutilation resembling the Lesch-Nyhan syndrome, but with normal uric acid levels, was treated with naloxone. Pain-inducing behavior decreased in the evenings following infusion of the drug, and was markedly reduced for 2 days following the treatment period. Though not recommended as therapy, the observations suggest that naloxone may play a role in the regulation of endorphin/enkephalin neural systems.
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PMID:Naloxone and self-mutilation. 629 9

Authors present a 10 year old boy with Lesch-Nyhan syndrome with self-inflicted mutilations to the lips, tongue and interior cheek wall, partially avoided by tooth extraction. Hand lesions were prevented by arm restriction. Born with anoxia and in spite of seizures for several years and a marked muscle stiffness, he is relatively aware of his surroundings. HGPRT activity in blood and hair was nil, while the APRT activity was increased. The mother, a maternal aunt and grandmother are not carriers. Hyperuricemia measured several times and treated with allopurinol is kept between 3 and 4 mg/dl and lastly under 3 mg after increasing dosage. Some years ago, elimination of acid uric stones in urine was observed without hematuria. It seems that recently stone elimination produced pain difficult to evaluate in this patient.
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PMID:[Report of a patient with Lesch-Nyhan syndrome caused by total deficiency of HGPRT and with normal activity in female family members]. 713 25

The Lesch-Nyhan syndrome (LNS) has been extensively studied from the genetic and biochemical point of view. The main characteristic of the syndrome is the self-mutilation feature, which has been poorly studied and understood. We propose a new hypothesis about the self-mutilation physiopathology, which is related to the supersensitivity of the dopaminergic D1 receptors in the neuromatrix found in the cingulum cortex region. The LNS shows an increase of uric acid levels as a result of the deficiency of hypoxanthine phosphoribosyltransferase enzyme. This increase could induce damage to dopaminergic neurons. As a consequence, a decrease in dopamine synthesis during gestation and the early postnatal period could occur, producing a functional dopaminergic denervation of the D1 receptors, located on the prefrontal cortex, specifically in the cingulum bundle projections. This phenomenon could induce a codification disturbance in the 'genetic body' of the neuromatrix, that could be expressed functionally as anosognosia, giving rise to self-mutilation. We suggest that this self-mutilation is a pain consciousness problem.
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PMID:Self-mutilation in the Lesch-Nyhan syndrome: a corporal consciousness problem?--a new hypothesis. 948 81

The prevalence of urolithiasis has been increasing for the past few decades in industrialized nations. Uric acid calculi account for a significant percentage of urinary stones. Certain risk factors may be involved in the pathogenesis of uric acid nephrolithiasis, including hyperuricosuria, low urinary volume, and persistently low urinary pH. Patients with medical conditions that promote profound hyperuricosuria are at high risk of developing uric acid calculi. These conditions include chronic diarrheal states; myeloproliferative disorders; insulin resistance, including diabetes mellitus; and monogenic metabolic disorders, such as Lesch-Nyhan syndrome. Computed tomography can provide a definitive diagnosis. Except in cases in which there is severe obstruction, progressive azotemia, serious infection, or unremitting pain, the initial treatment of patients with uric acid nephrolithiasis should be medical dissolution therapy because this approach is successful in the majority of cases. A thorough review of the epidemiology and pathophysiology of uric acid nephrolithiasis is crucial for the diagnosis, treatment, and prevention of stones in patients with this condition.
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PMID:Uric Acid nephrolithiasis: recent progress and future directions. 1739 68