{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T05:45:09Z","timestamp":1761975909865,"version":"3.40.5"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:sc>d<\/jats:sc>\u2010lactate, one of the isomers of lactate, exists in a low concentration in healthy individuals and it can be oxidized to pyruvate catalyzed by <jats:sc>d<\/jats:sc>\u2010lactate dehydrogenase. Excessive amount of <jats:sc>d<\/jats:sc>\u2010lactate causes <jats:sc>d<\/jats:sc>\u2010lactate acidosis associated with neurological manifestations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>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 <jats:italic>LDHD<\/jats:italic> gene, which encodes the <jats:sc>d<\/jats:sc>\u2010lactate dehydrogenase, consisting of a splice site variant c.469+1dupG and a missense variant c.752C&gt;T, p.(Thr251Met) which are pathogenic and likely pathogenic respectively according to the American College of Medical Genetics and Genomics (ACMG) classification. The serum <jats:sc>d<\/jats:sc>\u2010lactate level was subsequently detected to be elevated (0.61\u2009mmol\/L, reference value: 0\u20100.25\u2009mmol\/L).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the third report on <jats:italic>LDHD<\/jats:italic> mutations associated with <jats:sc>d<\/jats:sc>\u2010lactate 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 <jats:italic>LDHD<\/jats:italic> deficiency with the clinical presentations requires further investigations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmd2.12220","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T10:44:40Z","timestamp":1621593880000},"page":"15-22","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Human <scp>d<\/scp>\u2010lactate dehydrogenase deficiency by <i>LDHD<\/i> mutation in a patient with neurological manifestations and mitochondrial complex IV deficiency"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5133-1019","authenticated-orcid":false,"given":"Anna Ka\u2010Yee","family":"Kwong","sequence":"first","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheila Suet\u2010Na","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"},{"name":"Department of Paediatrics and Adolescent Medicine Hong Kong Children's Hospital  Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J. 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