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Neuropediatrics 2020; 51(02): 160-163
DOI: 10.1055/s-0039-3400976
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

Expanding Phenotypic Spectrum of Cerebral Aspartate–Glutamate Carrier Isoform 1 (AGC1) Deficiency

Brian Pfeiffer
1   Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Detroit, Michigan, United States
2   Division of Genetic, Genomic and Metabolic Disorders, Children's Hospital of Michigan, Detroit, Michigan, United States
,
Kuntal Sen 
3   Division of Neurogenetics and Developmental Pediatrics, Children's National Health System, Washington, District of Columbia, United States
,
Shagun Kaur
1   Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Detroit, Michigan, United States
2   Division of Genetic, Genomic and Metabolic Disorders, Children's Hospital of Michigan, Detroit, Michigan, United States
,
Kara Pappas
2   Division of Genetic, Genomic and Metabolic Disorders, Children's Hospital of Michigan, Detroit, Michigan, United States
4   Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan, United States
5   Department of Pathology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, United States
› Author Affiliations
Further Information

Publication History

06 June 2019

06 October 2019

Publication Date:
25 November 2019 (online)

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Abstract

Case We are reporting the third unrelated case of cerebral aspartate–glutamate carrier isoform 1 (AGC1) deficiency. Patient is a 21-month-old Yemeni male who presented with refractory seizure disorder and developmental arrest. Neuroimaging showed cerebral volume loss and diminished N-acetylaspartate (NAA) peak. Whole exome sequencing revealed a homozygous novel missense variant in the SLC25A12 gene. Patient's seizure frequency abated drastically following initiation of ketogenic diet.

Discussion and Conclusion Cerebral AGC1 deficiency results in dysfunction of mitochondrial malate aspartate shuttle, thereby prohibiting myelin synthesis. There are significant phenotypic commonalities between our patient and previously reported cases including intractable epilepsy, psychomotor delay, cerebral atrophy, and diminished NAA peak. Our report also provides evidence regarding beneficial effect of ketogenic diet in this rare neurometabolic epilepsy.

Keywords

SLC25A12 - aspartate–glutamate carrier - whole exome sequencing - ketogenic diet
 

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