Identification of human D lactate dehydrogenase deficiency.

Autor:	Monroe GR; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands.; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., van Eerde AM; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands.; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., Tessadori F; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands.; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands.; Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, 3584, CT, The Netherlands., Duran KJ; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands.; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., Savelberg SMC; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands.; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., van Alfen JC; Bartiméus, Institute for the Visually Impaired, Doorn, 3940, AB, The Netherlands., Terhal PA; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., van der Crabben SN; Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, 3584, EA, The Netherlands., Lichtenbelt KD; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., Fuchs SA; Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, 3584, EA, The Netherlands., Gerrits J; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., van Roosmalen MJ; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands.; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., van Gassen KL; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., van Aalderen M; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., Koot BG; Department of Pediatric Gastroenterology and Nutrition, Academic Medical Center, Amsterdam, 1105, AZ, The Netherlands., Oostendorp M; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands.; Laboratory of Clinical Chemistry, Deventer Hospital, Deventer, 7416, SE, The Netherlands., Duran M; Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, 1105, AZ, The Netherlands., Visser G; Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, 3584, EA, The Netherlands., de Koning TJ; Section of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, 9713, GZ, The Netherlands., Calì F; Oasi Research Institute-IRCCS, Troina, 94018, Italy., Bosco P; Oasi Research Institute-IRCCS, Troina, 94018, Italy., Geleijns K; Department of Child Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., de Sain-van der Velden MGM; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., Knoers NV; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands.; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., Bakkers J; Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, 3584, CT, The Netherlands.; Department of Medical Physiology, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., Verhoeven-Duif NM; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands.; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands., van Haaften G; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands. G.vanHaaften@umcutrecht.nl.; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands. G.vanHaaften@umcutrecht.nl., Jans JJ; Department of Genetics, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands.; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584, CX, The Netherlands.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2019 Apr 01; Vol. 10 (1), pp. 1477. Date of Electronic Publication: 2019 Apr 01.
DOI:	10.1038/s41467-019-09458-6
Abstrakt:	Phenotypic and biochemical categorization of humans with detrimental variants can provide valuable information on gene function. We illustrate this with the identification of two different homozygous variants resulting in enzymatic loss-of-function in LDHD, encoding lactate dehydrogenase D, in two unrelated patients with elevated D-lactate urinary excretion and plasma concentrations. We establish the role of LDHD by demonstrating that LDHD loss-of-function in zebrafish results in increased concentrations of D-lactate. D-lactate levels are rescued by wildtype LDHD but not by patients' variant LDHD, confirming these variants' loss-of-function effect. This work provides the first in vivo evidence that LDHD is responsible for human D-lactate metabolism. This broadens the differential diagnosis of D-lactic acidosis, an increasingly recognized complication of short bowel syndrome with unpredictable onset and severity. With the expanding incidence of intestinal resection for disease or obesity, the elucidation of this metabolic pathway may have relevance for those patients with D-lactic acidosis.
Databáze:	MEDLINE
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