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Molybdenum cofactor deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Molybdenum cofactor (MoCo) deficiency presents classically in the early neonatal period, with convulsions intractable to anticonvulsant therapy and coma. Without intubation and assisted ventilation, early neonatal death would be the outcome. Johnson and colleagues [1] reported in 1980 an extremely retarded girl in whom there was defective activity of both sulfite oxidase and xanthine oxidase. There were dislocated lenses. Urinary calculi were composed of xanthine, and excretion of hypoxanthine and xanthine were elevated. Urinary excretion of sulfite, thiosulfate, S-sulfocysteine, and taurine were increased. There was hypouricemia and decreased excretions of uric acid and sulfate. The primary defect was deficient synthesis of the MoCo.
Recent approaches to gout drug discovery: an update
Published in Expert Opinion on Drug Discovery, 2020
Naoyuki Otani, Motoshi Ouchi, Hideo Kudo, Shuichi Tsuruoka, Ichiro Hisatome, Naohiko Anzai
In 2017, Li et al. [33] reported that levels of GLUT9, which is encoded by the glucose transporter family gene SLC2A9, correlate with serum urate levels. Anzai et al. [34] analyzed GLUT9 in the Xenopus oocyte expression system and were the first to report that it is the voltage-driven urate efflux transporter URATv1. The transporter is present in the basolateral membrane of the proximal tubules [35]. Urate, which was taken up into the proximal tubules, is released on the vascular side by URATv1. Sever hypouricemia has been reported to be due to its mutation [36]. Thus, this transporter is also a potential drug discovery target.
Extreme hyperuricemia is a risk factor for infection-related deaths in incident dialysis patients: a multicenter prospective cohort study
Published in Renal Failure, 2020
Hiroyuki Yoshida, Daijo Inaguma, Eri Koshi-Ito, Soshiro Ogata, Akimitsu Kitagawa, Kazuo Takahashi, Shigehisa Koide, Hiroki Hayashi, Midori Hasegawa, Yukio Yuzawa, Naotake Tsuboi
In some previous studies, all-cause and CV-related mortality were found to be higher in patients with low serum UA levels; in addition, the mortality rate in patients with high serum UA levels was relatively lower than that of patients with low serum UA levels [24,26,39,40,41]. The results of previous studies were different from our results. We suppose that the differences arose from the cutoff values of the serum UA. Kim et al. indicated that the all-cause mortality rate was significantly low in patients with serum UA levels of ≥8.5 mg/dL [26]. Beberashvili et al. showed that the all-cause mortality rate was significantly low in hemodialysis patients with serum UA levels of ≥6.2 mg/dL [42]. Meanwhile, in our study, we divided the patients into five groups according to the serum UA levels, and the cutoff value of the group with the highest serum UA level was ≥12.0 mg/dL. The groups with the second and third highest serum UA levels in our study were comparable to the groups with serum UA levels of 6.2 and ≥8.5 mg/dL, respectively, in the previous studies. The all-cause mortality of these groups in our study was not very high. Therefore, we considered that patients with extremely high serum UA levels would have a poor survival. It is possible that there are other factors, such as malnutrition, associated with the higher mortality in patients with hypouricemia. Several studies have shown that a low serum UA level was related to nutritional and inflammatory markers [41,42,43]. Similarly, in this study, we could elucidate that the all-cause mortality in patients with the lowest serum UA level was high but not significantly higher than those of the other groups. The low levels of serum albumin, total cholesterol, and creatinine in the group with the lowest serum UA level might support this speculation.
Investigational drugs for hyperuricemia, an update on recent developments
Published in Expert Opinion on Investigational Drugs, 2018
Tristan Pascart, Pascal Richette
RLBN1001 was a prototype cancer drug that was found to induce significant hypouricemia in human patients. The hypouricemic potency of RLBN1001 and analogs was explored in 50 human subjects. Hypouricemia was induced by an increase in urate urinary excretion through strong inhibition of URAT1 and more modest inhibition of xanthine oxidase. These results have been presented in both 2014 EULAR and ACR meetings but have not been published so far [70].