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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rapid progress in the study of learning disabilities requires a common context within which investigators and professionals with very diverse backgrounds can work towards common goals. Much evidence points to the heterogeneity of origin and clinical expression of learning disabilities as well as to many other ways in which they resemble such multifactorial conditions as mental retardation, gout and hypertension. In these conditions, genetic and epidemiological methods have been used to sort out the constitutional and environmental factors which precipitate disease in susceptible persons. Such an approach to learning disabilities can be expected to be rewarding.
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PMID:The genetics of learning disabilities. 25 73

The Lesch--Nyhan syndrome is a heritable disorder of the metabolism of uric acid in which behavioral manifestations are prominent and among the most provocative. The mutated or variant gene that determines this disorder is carried on the X chromosome. The disease is expressed exclusively in males. The molecular expression of the abnormal gene is in the completely defective activity of the enzyme hypoxanthine guanine phosphoribosyl transferase. As a result these patients overproduce uric acid and may develop early in life many of the clinical findings we associate with gout. They have in addition a variety of neurological abnormalities including mental retardation, spastic cerebral palsy, and involuntary, choreoathetoid movements. Involved patients have unusual, compulsive, aggressive behavior. Its most prominent but by no means exclusive feature is self-mutilation. The central feature in the management of this behavior is physical restraint. A number of practical procedures have been learned which facilitate the care and feeding of these patients. Promising new findings suggest that behavioral modification using extinction techniques and pharmacologic methods utilizing agents designed to increase the effective cerebral content of serotonin may each have a place in the management of behavior in this syndrome.
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PMID:Behavior in the Lesch--Nyhan syndrome. 108 51

Five cases of early-onset gouty arthritis are presented, with roentgenographic abnormalities evident in the first two decades of life. Three patients suffered from "primary" gout; classification of the other two patients was difficlut because of associated mental retardation, hypothyroidism and psoriasis. Radiographic alterations included soft-tissue masses and calcification, with typical erosive abnormalities and predilection for the hands and feet. The sacroiliac joints were abnormal in two patients.
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PMID:Early-onset gouty arthritis. 120 73

Hypoxanthine-guanine phosphoribosyltransferase (HPRT, EC 2.4.2.8) is a purine salvage enzyme that catalyses the conversion of hypoxanthine and guanine to their respective mononucleotides. Partial deficiency of this enzyme can result in the overproduction of uric acid leading to a severe form of gout, whilst a virtual absence of HPRT activity causes the Lesch-Nyhan syndrome which is characterised by hyperuricaemia, mental retardation, choreoathetosis and compulsive self-mutilation. The HPRT-encoding gene is located on the X chromosome in the region q26-q27 and consists of nine exons and eight introns totalling 57 kb. This gene is transcribed to produce an mRNA of 1.6 kb, which contains a protein encoding region of 654 nucleotides. With the advent of increasingly refined techniques of molecular biology, it has been possible to study the HPRT gene of individuals with a deficiency in HPRT activity to determine the genetic basis of the enzyme deficiency. Many different mutations throughout the coding region have been described, but in the absence of precise information on the three-dimensional structure of the HPRT protein, it remains difficult to determine any consistent correlation between the structure and function of the enzyme.
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PMID:A review of the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. 148 31

Lesch--Nyhan syndrome is an X-linked disease caused by the deficiency of hypoxanthine phosphoribosyltransferase, an enzyme involved in the purine salvage pathways. It is characterized by severe gout, choreoathetosis, self-mutilatory behaviour and mental retardation. The derivation of mice genetically deficient in this enzyme may help to elucidate the pathogenesis of the neurological abnormality where previously models using drug administration to mimic the disorder have had to suffice.
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PMID:Mouse models of hypoxanthine phosphoribosyltransferase deficiency. 152 24

The authors report the second case of a female with typical Lesch-Nyhan syndrome. She exhibited athetoid movement, self-multilation, mental retardation and spasticity. Laboratory investigations revealed hyperuricaemia, hyperuricosuria and decreased erythrocyte hypoxanthine guanine phosphoribosyl transferase activity. She has normal female external genitalia and karyotype. Her parents are non-consanguineous and there is no family member with gout, nephropathy or any psychoneurological disorder. To prevent self-stimulation, it was necessary to fix the patient's upper extremities to the backrest of her wheelchair. The authors also describe an apparatus that limits elbow flexion.
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PMID:A female patient with Lesch-Nyhan syndrome. 161 15

Recent studies have confirmed that gout is an inborn error of metabolism. It has now become evident that the hyperuricemia associated with gout might occur either due to overproduction of uric acid, underexcretion of uric acid or a combination of these processes. Furthermore, patients with excessive purine synthesis may have a specific enzyme defect resulting in altered feedback inhibition of purine synthesis. A neurological disease manifest by mental retardation, choreo-athetosis, aggressive behavior, lip-biting and self-mutilation and associated with decidedly increased purine biosynthesis serves as a prototype of this kind of disorder. Other defects in regulation of purine biosynthesis have been postulated but their existence not yet confirmed. It has been demonstrated that urate crystals which are deposited from hyperuricemic body fluids set up an acute inflammatory reaction by means of a variety of chemical mediators. Thus, acute gouty arthritis is now recognized as an example of "crystal induced" synovitis. The treatment of gout consists of (1) the control of acute gouty attacks, and (2) the maintenance of normal serum uric acid concentrations. This latter may be achieved either with uricosuric drugs or with xanthine oxidase inhibition. With these principles in mind, it is now possible to avoid many of the severe crippling effects of gout and to restore the vast majority of gouty patients to useful and productive lives.
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PMID:Current concepts of hyperuricemia and gout. 577 83

Uric acid is the end product of purine metabolism in man. The findings of human pathological levels of uric acid in serum and urine have in most patients serious clinical implications. This paper summarizes aspects of uric acid examination in clinical biochemistry laboratory. The clinical consequences of pathological levels of uric acid are shown. Uric acid is a useful diagnostic tool as screening for most of purine metabolic disorders. The importance of uric acid measurement in plasma and urine with respect of metabolic disorders is highlighted. Not only gout and renal stones are indications to send blood to the laboratory for uric acid examination. Also familial nephritis, neurological abnormalities with mental retardation are reasons to know uric acid levels in blood and urine. The results underline the importance of urinary uric acid investigation, which is often quite overlooked, and is helpful in differential diagnosis of gout. This work is dedicated to Professor Jan Horbaczewsky and his 110th anniversary of the opening of lessons in medical chemistry at the Czech medical faculty of Charles University in Prague.
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PMID:The importance of uric acid examination. 886 10

A modelling approach is used to analyse diseases associated with purine metabolism in man. The specific focus is on deficiencies in two enzymes, hypoxanthine:guanine phosphoribosyltransferase and adenylosuccinate lyase. These deficiencies can lead to a number of symptoms, including neurological dysfunctions and mental retardation. Although the biochemical mechanisms of dysfunctions associated with adenylosuccinate lyase deficiency are not completely understood, there is at least general agreement in the literature about possible causes. Simulations with our model confirm that accumulation of the two substrates of the enzyme can lead to significant biochemical imbalance. In hypoxanthine:guanine phosphoribosyltransferase deficiency the biochemical mechanisms associated with neurological dysfunctions are less clear. Model analyses support some old hypotheses but also suggest new indicators for possible causes of neurological dysfunctions associated with this deficiency. Hypoxanthine:guanine phosphoribosyltransferase deficiency is known to cause hyperuricaemia and gout. We compare the relative importance of this deficiency with other known causes of gout in humans. The analysis suggests that defects in the excretion of uric acid are more consequential than defects in uric acid synthesis such as hypoxanthine:guanine phosphoribosyltransferase deficiency.
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PMID:Analysis of abnormalities in purine metabolism leading to gout and to neurological dysfunctions in man. 944 73

Hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficiency is an X-linked defect of purine metabolism. Clinical manifestations are usually related to the degree of enzyme deficiency; complete HPRT deficiency (Lesh-Nyhan Syndrome) presenting with severe neurological or renal symptoms, or partial HPRT deficiency (Kelley-Seegmiller syndrome) manifesting as a gout-urolithiasis syndrome. We report a case of partial HPRT deficiency presenting as chronic tophaceous gout, mental retardation, nephrolithiasis and family history suggestive of X-linked inheritance, for its rarity.
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PMID:Partial HPRT deficiency (Kelley-Seegmiller syndrome). 1664 40


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