Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC 2.4.2.8) is associated with a spectrum of disease that ranges from gouty arthritis (OMIM 300323) to the more severe Lesch-Nyhan syndrome (OMIM 300322). To date, all cases of HPRT deficiency have shown a mutation within the HPRT cDNA. In the present study of an individual with gout due to HPRT deficiency, we found a normal HPRT cDNA sequence. This is the first study to provide an example of HPRT deficiency which appears to be due to a defect in the regulation of the gene.
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PMID:Normal HPRT coding region in a male with gout due to HPRT deficiency. 1586 84

Lesch-Nyhan disease (LND) is a rare inherited disorder caused by mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT). LND is characterized by overproduction of uric acid, leading to gouty arthritis and nephrolithiasis. Affected patients also have characteristic neurological and behavioral anomalies. Multiple cell models have been developed to study the molecular and metabolic aspects of LND, and several animal models have been developed to elucidate the basis for the neurobehavioral syndrome. The models have different strengths and weaknesses rendering them suitable for studying different aspects of the disease. The extensive modeling efforts in LND have questioned the concept that an 'ideal' disease model is one that replicates all of its features because the pathogenesis of different elements of the disease involves different mechanisms. Instead, the modeling efforts have suggested a more fruitful approach that involves developing specific models, each tailored for addressing specific experimental questions.
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PMID:Lesch-Nyhan disease: from mechanism to model and back again. 1925 84

A deficiency in hypoxanthine guanine phosphoribosyltransferase (HPRT) activity leads to overproduction of uric acid. According to the degree of enzymatic deficiency, a large spectrum of neurologic features can also be observed, ranging from mild or no neurologic involvement to complete Lesch-Nyhan disease. Herein, we describe a patient with hyperuricemia, juvenile-onset gouty arthritis, nephrolithiasis, and mild neurologic symptoms, attributed to a newly identified variant of the hprt gene, c.596T>G, resulting in the amino acid change p.F199C. Residual HPRT activity (8%) protected against severe neurologic involvement in this patient. Modeling of the mutated protein was used to predict the mechanisms that led to partial enzymatic activity. Careful neurologic examination is warranted in juvenile and middle-aged patients with gout, in order to detect mild symptoms that may lead to a diagnosis of HPRT deficiency.
Arthritis Rheum 2009 Jul
PMID:Severe gouty arthritis and mild neurologic symptoms due to F199C, a newly identified variant of the hypoxanthine guanine phosphoribosyltransferase. 1956 99

Lesch-Nyhan syndrome is a rare sex-linked disorder of purine metabolism that is caused by a mutation in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene which causes marked hyperuricemia and hyperuricosuria, with signs of gouty arthritis and uric acid stone disease in early childhood. We report a case of renal pelvis calculi which was dissolved within 10 days of urine alkalinization and hydration.
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PMID:Urine alkalinization may be enough for the treatment of bilateral renal pelvis stones associated with Lesch-Nyhan syndrome. 2133 72

Gout, a common form of inflammatory arthritis, is strongly associated with elevated uric acid concentrations in the blood (hyperuricemia). A recent study in Icelanders identified a rare missense single nucleotide polymorphism (SNP) in the ALDH16A1 gene, ALDH16A1*2, to be associated with gout and serum uric acid levels. ALDH16A1 is a novel and rather unique member of the ALDH superfamily in relation to its gene and protein structures. ALDH16 genes are present in fish, amphibians, protista, bacteria but absent from archaea, fungi and plants. In most mammalian species, two ALDH16A1 spliced variants (ALDH16A1, long form and ALDH16A1_v2, short form) have been identified and both are expressed in HepG-2, HK-2 and HK-293 human cell lines. The ALDH16 proteins contain two ALDH domains (as opposed to one in the other members of the superfamily), four transmembrane and one coiled-coil domains. The active site of ALDH16 proteins from bacterial, frog and lower animals contain the catalytically important cysteine residue (Cys-302); this residue is absent from the mammalian and fish orthologs. Molecular modeling predicts that both the short and long forms of human ALDH16A1 protein would lack catalytic activity but may interact with the hypoxanthine-guanine phosphoribosyltransferase (HPRT1) protein, a key enzyme involved in uric acid metabolism and gout. Interestingly, such protein-protein interactions with HPRT1 are predicted to be impaired for the long or short forms of ALDH16A1*2. These results lead to the intriguing possibility that association between ALDH16A1 and HPRT1 may be required for optimal HPRT activity with disruption of this interaction possibly contributing to the hyperuricemia seen in ALDH16A1*2 carriers.
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PMID:ALDH16A1 is a novel non-catalytic enzyme that may be involved in the etiology of gout via protein-protein interactions with HPRT1. 2334 97

Lesch-Nyhan disease and its attenuated variants are caused by deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt). All patients exhibit excessive production of uric acid, which increases the risk for nephrolithiasis, renal failure, gouty arthritis and tophi. The mildest phenotype includes only problems related to overproduction of uric acid. The most severe clinical phenotype includes prominent neurological abnormalities and the universal feature is self-injurious behavior. In between the mildest and most severe syndromes is a broad spectrum of phenotypes with varying degrees of neurological, neurocognitive and behavioral abnormalities. The effect of HPRT1 gene mutations on residual HGprt enzyme activity is the most relevant factor contributing to disease phenotype. Attenuated clinical phenotypes are associated with residual enzyme function, whereas the most severe phenotype is usually associated with null activity. In cases of gouty arthritis with urate overproduction, a careful evaluation for motor impairments or neurocognitive abnormalities may help to identify attenuated variants of Lesch-Nyhan disease for better management.
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PMID:Genotypic and phenotypic spectrum in attenuated variants of Lesch-Nyhan disease. 2493 28

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (EC 2.4.2.8) reversibly catalyzes the transfer of the 5-phophoribosyl group from 5-phosphoribosyl-alpha-1-pyrophosphate (PRPP) to hypoxanthine or guanine to form inosine monophosphate (IMP) or guanosine monophosphate (GMP) in the purine salvage pathway. To investigate the catalytic mechanism of this enzyme in the intracellular pathogen Legionella pneumophila, we determined the crystal structures of the L. pneumophila HGPRT (LpHGPRT) both in its apo-form and in complex with GMP. The structures reveal that LpHGPRT comprises a core domain and a hood domain which are packed together to create a cavity for GMP-binding and the enzymatic catalysis. The binding of GMP induces conformational changes of the stable loop II. This new binding site is closely related to the Gout arthritis-linked human HGPRT mutation site (Ser103Arg). Finally, these structures of LpHGPRT provide insights into the catalytic mechanism of HGPRT.
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PMID:Crystal structures of Apo and GMP bound hypoxanthine-guanine phosphoribosyltransferase from Legionella pneumophila and the implications in gouty arthritis. 2696 65

Purine metabolism in the human body leads to the production of uric acid (UA) at the end. But an abnormal level of UA in the human body creates health problems. The sensing and quantification of UA is essentially required to prevent and diagnose hypertension, arthritis, gout, hyperuricemia or Lesch-Nyhan syndrome, etc. Herein, the development of a sensing platform for the measurement of UA using Au nanoparticle-based hybrid self-assembly is described. The self-assembling of a thiol-terminated silicate network functionalized graphene oxide hybrid on a polycrystalline Au surface yields a three-dimensional assembly. The oxygen functionalities of the self-assembly were partially reduced by an NaBH4 treatment. The free -SH groups of the self-assembly were successfully used for the immobilization of Au nanoparticles by chemisorption. The nanoparticle-based hybrid self-assembly is highly sensitive toward UA, and shows a wide linear response with a detection limit of 40 nM UA (S/N = 7) without interference from co-exiting ascorbic acid. Its practical application was demonstrated using human serum samples.
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PMID:Reduced Graphene Oxide-based Covalent Hybrid Film Electrode Self-assembled with Gold Nanoparticles for the Enzyme-Free Amperometric Sensing of Serum Uric Acid. 3144 70


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