Genetic Basis of the Epidemiological Features and Clinical Significance of Renal Hypouricemia
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ABSTRACT:
SUBMITTER: Hakoda M
PROVIDER: S-EPMC9313227 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Renal hypouricemia (RHUC) is a disease caused by dysfunction of renal urate reabsorption transporters; however, diagnostic guidance and guidelines for RHUC have been lacking, partly due to the low evidence level of studies on RHUC. This review describes a world-first clinical practice guideline (CPG) and its first version in English for this condition. It was developed following the "MINDS Manual for Guideline Development" methodology, which prioritizes evidence-based medicine. It was published in Japanese in 2017 and later translated into English. The primary goal of this CPG is to clarify the criteria for diagnosing RHUC; another aim is to work towards a consensus on clinical decision-making. One of the CPG's unique points is that it contains textbook descriptions at the expert consensus level, in addition to two clinical questions and recommendations derived from a systematic review of the literature. The guidance shown in this CPG makes it easy to diagnose RHUC from simple blood and urine tests. This CPG contains almost all of the clinical foci of RHUC: epidemiology, pathophysiology, diagnostic guidance, clinical examinations, differential diagnosis, and complications, including exercise-induced acute kidney injury and urolithiasis. A CPG summary as well as a clinical algorithm to assist healthcare providers with a quick reference and notes from an athlete for both physicians and patients are included. We hope that this CPG will help healthcare providers and patients to make clinical decisions, and that it will promote further research on RHUC.
| S-EPMC6437292 | biostudies-literature
Project description:The SARS-CoV-2 Omicron (B.1.1529) variant was designated as a variant of concern (VOC) by the World Health Organization (WHO) on November 26, 2021. Within two months, it had replaced the Delta variant and had become the dominant circulating variant around the world. The Omicron variant possesses an unprecedented number of mutations, especially in the spike protein, which may be influencing its biological and clinical aspects. Preliminary studies have suggested that increased transmissibility and the reduced protective effects of neutralizing antibodies have contributed to the rapid spread of this variant, posing a significant challenge to control the coronavirus disease 2019 (COVID-19) pandemic. There is, however, a silver lining for this wave of the Omicron variant. A lower risk of hospitalization and mortality has been observed in prevailing countries. Booster vaccination also has ameliorated a significant reduction in neutralization. Antiviral drugs are minimally influenced. Moreover, the functions of Fc-mediated and T-cell immunity have been retained to a great extent, both of which play a key role in preventing severe disease.
| S-EPMC9099228 | biostudies-literature
Project description:Recent developments in molecular diagnostic tools have led to the easy and rapid detection of a large number of rhinovirus (HRV) strains. However, the lack of clinical and epidemiological data hampers the interpretation of these diagnostic findings. From October 2009 to January 2011, we conducted a prospective study in hospitalized children from whom samples were taken for the detection of respiratory viruses. Clinical, epidemiological and microbiological data from 644 patients with 904 disease episodes were collected. When HRV tested positive, strains were further characterized by sequencing the VP4/VP2 region of the HRV genome. HRV was the single respiratory virus detected in 254 disease episodes (28%). Overall, 99 different serotypes were detected (47% HRV-A, 12% HRV-B, 39% HRV-C). Patients with HRV had more underlying pulmonary illness compared with patients with no virus (p 0.01), or patients with another respiratory virus besides HRV (p 0.007). Furthermore, cough, shortness of breath and a need for oxygen were significantly more present in patients with HRV infection. Particularly, patients with HRV-B required extra oxygen. No respiratory symptom, except for oxygen need, was predictive of the presence of HRV. In 22% of HRV-positive disease episodes, HRV infection was hospital acquired. Phylogenetic analysis revealed several clusters of HRV; in more than 25% of these clusters epidemiological information was suggestive of transmission within specific wards. In conclusion, the detection of HRV may help in explaining respiratory illness, particular in patients with pulmonary co-morbidities. Identifying HRV provides opportunities for timely implementation of infection control measures to prevent intra-hospital transmission.
| S-EPMC7129489 | biostudies-literature
Project description:Differentiating between inherited renal hypouricemia and transient hypouricemic status is challenging. Here, we aimed to describe the genetic background of hypouricemia patients using whole-exome sequencing (WES) and assess the feasibility for genetic diagnosis using two founder variants in primary screening. We selected all cases (N = 31) with extreme hypouricemia (<1.3 mg/dl) from a Korean urban cohort of 179,381 subjects without underlying conditions. WES and corresponding downstream analyses were performed for the discovery of rare causal variants for hypouricemia. Two known recessive variants within SLC22A12 (p.Trp258*, pArg90His) were identified in 24 out of 31 subjects (77.4%). In an independent cohort, we identified 50 individuals with hypouricemia and genotyped the p.Trp258* and p.Arg90His variants; 47 of the 50 (94%) hypouricemia cases were explained by only two mutations. Four novel coding variants in SLC22A12, p.Asn136Lys, p.Thr225Lys, p.Arg284Gln, and p.Glu429Lys, were additionally identified. In silico studies predict these as pathogenic variants. This is the first study to show the value of genetic diagnostic screening for hypouricemia in the clinical setting. Screening of just two ethnic-specific variants (p.Trp258* and p.Arg90His) identified 87.7% (71/81) of Korean patients with monogenic hypouricemia. Early genetic identification of constitutive hypouricemia may prevent acute kidney injury by avoidance of dehydration and excessive exercise.
| S-EPMC6779878 | biostudies-literature
Project description:Hypouricemia is defined as a level of serum uric acid below 2 mg/dl. Renal hypouricemia is related to genetic defects of the uric acid tubular transporters urate transporter 1 and glucose transporter 9. Patients with renal hypouricemia can be completely asymptomatic or can develop uric acid kidney stones or acute kidney injury, particularly after exercise. Renal hypouricemia is especially challenging to diagnose in patients with acute kidney injury, due to the nonspecific clinical, hematochemical and histological features. No common features are reported in the literature that could help clinicians identify renal hypouricemia-acute kidney injury. Currently available guidelines on diagnosis and management of renal hypouricemia provide limited support in defining clues for the differential diagnosis of renal hypouricemia, which is usually suspected when hypouricemia is found in asymptomatic patients. In this paper we report a case of renal hypouricemia-acute kidney injury developing after exercise. We carried out a review of the literature spanning from the first clinical description of renal hypouricemia in 1974 until 2022. We selected a series of clinical features suggesting a diagnosis of renal hypouricemia-acute kidney injury. This may help clinicians to suspect renal hypouricemia in patients with acute kidney injury and to avoid invasive, costly and inconclusive exams such as renal biopsy. Considering the excellent outcome of the patients reported in the literature, we suggest a "wait-and-see" approach with supportive therapy and confirmation of the disease via genetic testing.
| S-EPMC10089983 | biostudies-literature
Project description:BackgroundRubinstein-Taybi syndrome (RSTS) is an extremely rare autosomal dominant genetic disease, with an estimated prevalence of one case per 125,000 live births. RSTS is characterized by typical facial features, microcephaly, broad thumbs and first toes, intellectual disability, and postnatal growth retardation. However, no standard diagnostic criteria are available for RSTS. In this review, we summarized the clinical features and genetic basis of RSTS and highlighted areas for future studies on an appropriate diagnostic protocol and follow-up care for RSTS.DiscussionRSTS is primarily characterized by delayed growth in height and weight, microcephaly, dysmorphic facial features, and broad thumbs and big toe. Over 90% RSTS individuals with disabilities survive to adulthood, but healthcare for these patients is particularly complex, time-consuming, and costly. In addition, no standard diagnostic criteria and follow-up care guidelines are available for RSTS. It has been shown that mutations in the genes encoding the cyclic-AMP-regulated enhancer binding protein (CREBBP) and the E1A-binding protein p300 (EP300) contributed to the development of RSTS. Therefore, genetic tests are useful for the diagnosis of RSTS, although most RSTS cases are currently diagnosed based on clinical features. The clinical features of RSTS have been extensively studied, which significantly contributes to the diagnosis of this extremely rare syndrome. However, the pathogenesis and genotype-phenotype associations of RSTS are largely unknown. Therefore, multicenter studies and international cooperation are highlighted for better understanding of this disease, establishing standard diagnostic criteria, and providing professional management and follow-up care of RSTS.
| S-EPMC4308897 | biostudies-literature
Project description:Hereditary hypouricemia may result from mutations in the renal tubular uric acid transporter URAT1. Whether mutation of other uric acid transporters produces a similar phenotype is unknown. We studied two families who had severe hereditary hypouricemia and did not have a URAT1 defect. We performed a genome-wide homozygosity screen and linkage analysis and identified the candidate gene SLC2A9, which encodes the glucose transporter 9 (GLUT9). Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. In vitro, the L75R mutation dramatically impaired transport of uric acid. The mean concentration of serum uric acid of seven homozygous individuals was 0.17 +/- 0.2 mg/dl, and all had a fractional excretion of uric acid >150%. Three individuals had nephrolithiasis, and three had a history of exercise-induced acute renal failure. In conclusion, homozygous loss-of-function mutations of GLUT9 cause a total defect of uric acid absorption, leading to severe renal hypouricemia complicated by nephrolithiasis and exercise-induced acute renal failure. In addition to clarifying renal handling of uric acid, our findings may provide a better understanding of the pathophysiology of acute renal failure, nephrolithiasis, hyperuricemia, and gout.
| S-EPMC2799278 | biostudies-literature
Project description:Renal hypouricemia (RHUC) is a rare autosomal recessive disorder characterized by impaired renal tubular uric acid reabsorption and abnormally high uric acid clearance, which may be manifested by reduced serum uric acid (SUA) levels and elevated fractional excretion of uric acid (FE-UA >10%). Most RHUC patients are often asymptomatic or have accidentally decreased SUA levels during health examinations, while others develop kidney stones and exercise-induced acute kidney injury (EIAKI). We now report a case of RHUC complicated with an asymptomatic kidney stone, and we identified a heterozygous mutation of c.269G > A (p.R90H) and a novel heterozygous mutation of c.674C > G (p.T225R) in the SLC22A12 gene in the patient through whole exon gene detection (NGS method). This case offers valuable insights into the mechanisms, clinical management, and prognosis of RHUC and its associated complications.
| S-EPMC10878990 | biostudies-literature
Project description:The cutaneous dermatomycoses are among topical issues in all countries worldwide. They are registered in 20% of the world population. Dermatophyte infections incidence frequency varies depending on a season, region, effective anti-epidemic measures management, and effective treatment methods. In Kazakhstan in 2001, dermatophyte infections ranked second in the structure of dermatologic pathology in outpatients. According to the literature data, not so many research studies on dermatophyte infections have been carried out in our country within recent years. The importance of these issues suggests a need to conduct epidemiological, clinical, microbiological studies of dermatophytosis at the present stage. A cross-sectional study was conducted, in which 195 cases of dermatophytosis were collected and investigated in the regional hospital in Almaty for the period from the beginning of January 2014 to the end of December 2014. Dermatophytoses prevalence is observed in patients within the 1 - 39 age range.
| S-EPMC5535645 | biostudies-other
Project description:BackgroundLaboratory diagnosis of hemorrhagic fever with renal syndrome (HFRS), an infectious disease caused by rodent-borne hantaviruses in Asia and Europe, depends primarily on serological methods. Since the advent of such serodiagnostic tests, few reports are available about the clinical and molecular epidemiological features of HFRS.ObjectivesTo investigate the epidemioclinical features of HFRS patients treated at a tertiary-care teaching hospital in Seoul over a 10-year period.Study designMedical records of HFRS patients, admitted to a tertiary-care teaching hospital during February 2002 to February 2012, were reviewed. Sera from patients were tested for Hantaan virus (HTNV) and Seoul virus (SEOV) RNA using RT-PCR.ResultsAmong 35 HFRS patients (mean age was 44.2±14.7 years), 29 were male (82.9%). Acute renal failure developed in 27 patients (77.1%), and 12 patients (34.3%) were admitted to the intensive care unit (ICU). Conjunctival injection (OR 10.32, 95% CI 1.09-97.77, P=.04) and initial serum albumin less than 3g/dL (OR 22.83, 95% CI 1.45-359.93, P=.03) were risk factors for ICU admission. Of 35 acute-phase sera, 11 (31.4%) were positive for HTNV RNA. None were positive for SEOV RNA.ConclusionsHFRS was characterized by the clinical triad of fever, renal insufficiency and gastrointestinal symptoms. Conjunctival injection and serum albumin level were related to severity. A large-scale multi-center study is needed to enhance insights into epidemioclinical characteristics of HFRS in Korea.
| S-EPMC4153883 | biostudies-literature