Identification of human D lactate dehydrogenase deficiency

Research output: Contribution to journalArticle


title = "Identification of human D lactate dehydrogenase deficiency",
abstract = "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{\textquoteright} variant LDHD, confirming these variants{\textquoteright} 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.",
author = "Monroe, {Glen R.} and {van Eerde}, {Albertien M.} and Federico Tessadori and Duran, {Karen J.} and Savelberg, {Sanne M.C.} and {van Alfen}, {Johanna C.} and Terhal, {Paulien A.} and {van der Crabben}, {Saskia N.} and Lichtenbelt, {Klaske D.} and Fuchs, {Sabine A.} and Johan Gerrits and {van Roosmalen}, {Markus J.} and {van Gassen}, {Koen L.} and {van Aalderen}, Mirjam and Koot, {Bart G.} and Marlies Oostendorp and Marinus Duran and Gepke Visser and {de Koning}, {Tom J.} and Francesco Cal{\`i} and Paolo Bosco and Karin Geleijns and {de Sain-van der Velden}, {Monique G.M.} and Knoers, {Nine V.} and Jeroen Bakkers and Verhoeven-Duif, {Nanda M.} and {van Haaften}, Gijs and Jans, {Judith J.}",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-09458-6",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",