Hyperuricemia and gout caused by missense mutation in d-lactate dehydrogenase

Drabkin, Max; Yogev, Yuval; Zeller, Lior; Zarivach, Raz; Zalk, Ran; Halpérin, Daniel; Wormser, Ohad; Gurevich, Evgenia; Landau, Daniel; Kadir, Rotem; Perez, Yonatan

doi:10.1172/jci129057

Cited by 30 publications

(26 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, elevation of d ‐lactate associated with neurological phenotypes has been reported in two patients with d ‐lactate dehydrogenase deficiency resulting from LDHD mutations 1 . So far, there are only two studies reporting LDHD mutations associated with d ‐lactate elevation 1,11 . Here, we report another patient with LDHD mutations with increased serum d ‐lactate level.…”

Section: Introductionmentioning

confidence: 63%

Human d‐lactate dehydrogenase deficiency by LDHD mutation in a patient with neurological manifestations and mitochondrial complex IV deficiency

et al. 2021

View full text Add to dashboard Cite

Background d‐lactate, one of the isomers of lactate, exists in a low concentration in healthy individuals and it can be oxidized to pyruvate catalyzed by d‐lactate dehydrogenase. Excessive amount of d‐lactate causes d‐lactate acidosis associated with neurological manifestations. Methods and Results We report here a patient with developmental delay, cerebellar ataxia, and transient hepatomegaly. Enzyme analysis in the patient's skin fibroblast showed decreased mitochondrial complex IV activity. Using whole exome sequencing, we identified compound heterozygous variants in the LDHD gene, which encodes the d‐lactate dehydrogenase, consisting of a splice site variant c.469+1dupG and a missense variant c.752C>T, p.(Thr251Met) which are pathogenic and likely pathogenic respectively according to the American College of Medical Genetics and Genomics (ACMG) classification. The serum d‐lactate level was subsequently detected to be elevated (0.61 mmol/L, reference value: 0‐0.25 mmol/L). Conclusion This is the third report on LDHD mutations associated with d‐lactate elevation and was first reported to have decreased mitochondrial complex IV activity. The study provides more information on this rare metabolic condition but the association of LDHD deficiency with the clinical presentations requires further investigations.

show abstract

Section: Introductionmentioning

confidence: 63%

Human d‐lactate dehydrogenase deficiency by LDHD mutation in a patient with neurological manifestations and mitochondrial complex IV deficiency

et al. 2021

View full text Add to dashboard Cite

show abstract

“…As a consequence, excessive renal secretion of d-lactate in exchange for UA reabsorption culminates in HU. In line with the human phenotype, injection of d-lactate into naive mice resulted in HU [20].…”

Section: Genetics: Possibilities For Individualized Diagnoses and Care Strategies?mentioning

confidence: 94%

“…Among many others, one should acknowledge organic anion transporters 10 (OAT10, SLC22A13), acting as a key part of urate transport from urine to the blood; lactate dehydrogenase D (LDHD), decreasing excretion of UA [20]; hypoxanthine-guanine phosphoribosyltransferase (HGPRT) whose deficiency caused by an HPRT1 mutation leads to elevated UA levels in the blood, which are associated with Kelley-Seegmiller syndrome, Lesch-Nyhan syndrome, and HU [21]; mitochondrial seryl-tRNA synthetase precursor, a member of the class II tRNA synthetase family, which is involved in the ligation of serine to tRNA (Ser) and is involved in selenocysteinyl-tRNA (sec) biosynthesis in mitochondria [22]; xanthine dehydrogenase (XDH), influencing the oxidation of hypoxanthine to xanthine and the oxidation of xanthine to UA [23], therefore reducing the levels of xanthine oxidoreductase. Drabkin et al [20] confirmed that a mutation could cause HU in LDHD within the putative catalytic site of the encoded d-lactate dehydrogenase, which results in increased blood levels of d-lactate -typically present in blood in miniscule amounts. As a consequence, excessive renal secretion of d-lactate in exchange for UA reabsorption culminates in HU.…”

Section: Genetics: Possibilities For Individualized Diagnoses and Care Strategies?mentioning

confidence: 99%

Expert consensus for the diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk: 2021 update

et al. 2021

View full text Add to dashboard Cite

show abstract

“…[ 10 ] Gene mutations and polymorphisms are the genetic basis for the increase in gout. [ 11 ] Immunity and inflammation are involved in the pathogenesis of gout. [ 12 – 14 ]…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of pricking-blood therapy for acute gouty arthritis

Zhang

et al. 2020

Medicine

View full text Add to dashboard Cite

Background: Acute gouty arthritis is a joint inflammatory reaction that affects the daily quality of patients. Previous reviews of pricking-blood therapy for acute gouty arthritis have been growing, but a systematic review is not available. This study aimed to systematically investigate the efficacy and safety of pricking-blood therapy in treating acute gout arthritis. Methods: We will search for relevant literature through Chinese and English databases, with the retrieval deadline being December 2020. Databases include PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Database, and China Biomedical Literature Database. We will also manually search Chinese Acupuncture & Moxibustion , Acupuncture Research, Chinese Clinical Trial Register, and unpublished studies or references. According to the inclusion and exclusion criteria, the literature will be screened, and the data are extracted independently by the 2 researchers. The primary outcomes were the total effective rate and Visual Analogue Scale (VAS) score. RevMan 5.3.5. software will be used for statistical analysis. According to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE), each evidence of outcome quality will be appraised. Results: This study will provide a comprehensive review of current evidence for a pricking-blood therapy treatment for acute gouty arthritis. Conclusion: The efficacy and safety of picking-blood therapy in treating acute gout arthritis will be evaluated. Unique INPLASY number: INPLASY2020100094.

show abstract

Hyperuricemia and gout caused by missense mutation in d-lactate dehydrogenase

Cited by 30 publications

References 35 publications

Human d‐lactate dehydrogenase deficiency by LDHD mutation in a patient with neurological manifestations and mitochondrial complex IV deficiency

Human d‐lactate dehydrogenase deficiency by LDHD mutation in a patient with neurological manifestations and mitochondrial complex IV deficiency

Expert consensus for the diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk: 2021 update

Efficacy and safety of pricking-blood therapy for acute gouty arthritis

Contact Info

Product

Resources

About