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Expanding the Clinical Spectrum of Mitochondrial Citrate Carrier (SLC25A1) Deficiency: Facial Dysmorphism in Siblings with Epileptic Encephalopathy and Combined D,L-2-Hydroxyglutaric Aciduria

  • Pankaj Prasun
  • Sarah Young
  • Gajja Salomons
  • Andrea Werneke
  • Yong-hui Jiang
  • Eduard Struys
  • Mikell Paige
  • Maria Laura Avantaggiati
  • Marie McDonaldEmail author
Case Report
Part of the JIMD Reports book series (JIMD, volume 19)

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.

Keywords

Lactic acidosis Mitochondrial citrate carrier Mitochondria SLC25A1 2-hydroxyglutaric aciduria dysmorphism 

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Pankaj Prasun
    • 1
  • Sarah Young
    • 1
    • 2
  • Gajja Salomons
    • 3
  • Andrea Werneke
    • 2
  • Yong-hui Jiang
    • 1
  • Eduard Struys
    • 3
  • Mikell Paige
    • 4
  • Maria Laura Avantaggiati
    • 5
  • Marie McDonald
    • 1
    Email author
  1. 1.Divison of Medical Genetics, Department of PediatricsDuke University Medical CenterDurhamUSA
  2. 2.Biochemical Genetics LaboratoryDuke University Health SystemDurhamUSA
  3. 3.Metabolic Unit, Department of Clinical ChemistryVU University Medical CenterAmsterdamThe Netherlands
  4. 4.Department of Chemistry and BiochemistryGeorge Mason UniversityManassasUSA
  5. 5.Lombardi Cancer CenterGeorgetown UniversityWashington, DCUSA

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