Abstract
Recessive mutations in SLC25A1 encoding mitochondrial citrate carrier cause a rare inherited metabolic disorder, combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA), characterized by epileptic encephalopathy, respiratory insufficiency, developmental arrest and early death. Here, we describe two siblings compound heterozygotes for null/missense SLC25A1 mutations, c.18_24dup (p.Ala9Profs*82), and c.134C>T (p.Pro45Leu). These children presented with classic clinical features of D,L-2-HGA, but also showed marked facial dysmorphism. Additionally, there was prominent lactic acidosis in one of the siblings. Our observations suggest that facial dysmorphism is a previously unrecognized but an important diagnostic feature of SLC25A1 deficiency and expand the clinical phenotype linked to SLC25A1 mutations.
Competing interests: None declared
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Communicated by: Francois Feillet, MD, PhD
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This clinical report is a retrospective clinical observation that does not require ethics committee approval at this institution.
There are no prior publications of this manuscript.
The work is not and will not be submitted to any other journal while under consideration by “JIMD.”
The authors, Pankaj Prasun, Sarah Young, Gajja Salomons, Andrea Werneke, Yong-hui Jiang, Eduard Struys, Mikell Paige, Maria Laura Avantaggiati, and Marie McDonald, have no potential conflicting or competing interests that could in any way affect the conduct of the study, interpretation of results, or preparation of the manuscript.
The authors, Pankaj Prasun, Sarah Young, Gajja Salomons, Andrea Werneke, Yong-hui Jiang, Eduard Struys, Mikell Paige, Maria Laura Avantaggiati, and Marie McDonald, do not have any funding sources to declare related to the study and to the article preparation.
Dr. Pankaj Prasun was involved in patient care, laboratory interpretation, initial drafting of the manuscript, and revisions of each draft.
Dr. Sarah young was involved in laboratory interpretation and revising the manuscript critically for important intellectual content.
Dr. Gajja Salomons was involved in laboratory interpretation and revisions of each draft.
Ms. Andrea Werneke was involved in laboratory interpretation and revisions of each draft.
Dr. Yong-hui Jiang was involved in patient care, laboratory interpretation, and revisions of each draft.
Dr. Eduard Struys was involved in laboratory interpretation and revisions of each draft.
Dr. Mikell Paige was involved in laboratory interpretation, drafting of cartoon, and revisions of each draft.
Dr. Maria Laura Avantaggiati was involved in laboratory interpretation, drafting of cartoon, and revising the manuscript critically for important intellectual content.
Dr. Marie McDonald supervised the case report and was involved in patient care, laboratory interpretation, and revising the manuscript critically for important intellectual content.
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Prasun, P. et al. (2014). Expanding the Clinical Spectrum of Mitochondrial Citrate Carrier (SLC25A1) Deficiency: Facial Dysmorphism in Siblings with Epileptic Encephalopathy and Combined D,L-2-Hydroxyglutaric Aciduria. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 19. JIMD Reports, vol 19. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_378
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DOI: https://doi.org/10.1007/8904_2014_378
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