Identification of human D lactate dehydrogenase deficiency

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Identification of human D lactate dehydrogenase deficiency. / Monroe, Glen R.; van Eerde, Albertien M.; Tessadori, Federico; Duran, Karen J.; Savelberg, Sanne M.C.; van Alfen, Johanna C.; Terhal, Paulien A.; van der Crabben, Saskia N.; Lichtenbelt, Klaske D.; Fuchs, Sabine A.; Gerrits, Johan; van Roosmalen, Markus J.; van Gassen, Koen L.; van Aalderen, Mirjam; Koot, Bart G.; Oostendorp, Marlies; Duran, Marinus; Visser, Gepke; de Koning, Tom J.; Calì, Francesco; Bosco, Paolo; Geleijns, Karin; de Sain-van der Velden, Monique G.M.; Knoers, Nine V.; Bakkers, Jeroen; Verhoeven-Duif, Nanda M.; van Haaften, Gijs; Jans, Judith J.

In: Nature Communications, Vol. 10, No. 1, 1477, 01.12.2019.

Research output: Contribution to journalArticle

Harvard

Monroe, GR, van Eerde, AM, Tessadori, F, Duran, KJ, Savelberg, SMC, van Alfen, JC, Terhal, PA, van der Crabben, SN, Lichtenbelt, KD, Fuchs, SA, Gerrits, J, van Roosmalen, MJ, van Gassen, KL, van Aalderen, M, Koot, BG, Oostendorp, M, Duran, M, Visser, G, de Koning, TJ, Calì, F, Bosco, P, Geleijns, K, de Sain-van der Velden, MGM, Knoers, NV, Bakkers, J, Verhoeven-Duif, NM, van Haaften, G & Jans, JJ 2019, 'Identification of human D lactate dehydrogenase deficiency', Nature Communications, vol. 10, no. 1, 1477. https://doi.org/10.1038/s41467-019-09458-6

APA

Monroe, G. R., van Eerde, A. M., Tessadori, F., Duran, K. J., Savelberg, S. M. C., van Alfen, J. C., Terhal, P. A., van der Crabben, S. N., Lichtenbelt, K. D., Fuchs, S. A., Gerrits, J., van Roosmalen, M. J., van Gassen, K. L., van Aalderen, M., Koot, B. G., Oostendorp, M., Duran, M., Visser, G., de Koning, T. J., ... Jans, J. J. (2019). Identification of human D lactate dehydrogenase deficiency. Nature Communications, 10(1), [1477]. https://doi.org/10.1038/s41467-019-09458-6

CBE

Monroe GR, van Eerde AM, Tessadori F, Duran KJ, Savelberg SMC, van Alfen JC, Terhal PA, van der Crabben SN, Lichtenbelt KD, Fuchs SA, Gerrits J, van Roosmalen MJ, van Gassen KL, van Aalderen M, Koot BG, Oostendorp M, Duran M, Visser G, de Koning TJ, Calì F, Bosco P, Geleijns K, de Sain-van der Velden MGM, Knoers NV, Bakkers J, Verhoeven-Duif NM, van Haaften G, Jans JJ. 2019. Identification of human D lactate dehydrogenase deficiency. Nature Communications. 10(1):Article 1477. https://doi.org/10.1038/s41467-019-09458-6

MLA

Vancouver

Monroe GR, van Eerde AM, Tessadori F, Duran KJ, Savelberg SMC, van Alfen JC et al. Identification of human D lactate dehydrogenase deficiency. Nature Communications. 2019 Dec 1;10(1). 1477. https://doi.org/10.1038/s41467-019-09458-6

Author

Monroe, Glen R. ; van Eerde, Albertien M. ; Tessadori, Federico ; Duran, Karen J. ; Savelberg, Sanne M.C. ; van Alfen, Johanna C. ; Terhal, Paulien A. ; van der Crabben, Saskia N. ; Lichtenbelt, Klaske D. ; Fuchs, Sabine A. ; Gerrits, Johan ; van Roosmalen, Markus J. ; van Gassen, Koen L. ; van Aalderen, Mirjam ; Koot, Bart G. ; Oostendorp, Marlies ; Duran, Marinus ; Visser, Gepke ; de Koning, Tom J. ; Calì, Francesco ; Bosco, Paolo ; Geleijns, Karin ; de Sain-van der Velden, Monique G.M. ; Knoers, Nine V. ; Bakkers, Jeroen ; Verhoeven-Duif, Nanda M. ; van Haaften, Gijs ; Jans, Judith J. / Identification of human D lactate dehydrogenase deficiency. In: Nature Communications. 2019 ; Vol. 10, No. 1.

RIS

TY - JOUR

T1 - Identification of human D lactate dehydrogenase deficiency

AU - Monroe, Glen R.

AU - van Eerde, Albertien M.

AU - Tessadori, Federico

AU - Duran, Karen J.

AU - Savelberg, Sanne M.C.

AU - van Alfen, Johanna C.

AU - Terhal, Paulien A.

AU - van der Crabben, Saskia N.

AU - Lichtenbelt, Klaske D.

AU - Fuchs, Sabine A.

AU - Gerrits, Johan

AU - van Roosmalen, Markus J.

AU - van Gassen, Koen L.

AU - van Aalderen, Mirjam

AU - Koot, Bart G.

AU - Oostendorp, Marlies

AU - Duran, Marinus

AU - Visser, Gepke

AU - de Koning, Tom J.

AU - Calì, Francesco

AU - Bosco, Paolo

AU - Geleijns, Karin

AU - de Sain-van der Velden, Monique G.M.

AU - Knoers, Nine V.

AU - Bakkers, Jeroen

AU - Verhoeven-Duif, Nanda M.

AU - van Haaften, Gijs

AU - Jans, Judith J.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85063734330&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-09458-6

DO - 10.1038/s41467-019-09458-6

M3 - Article

C2 - 30931947

AN - SCOPUS:85063734330

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1477

ER -