Abstract
Glutaric aciduria type II, also known as Multiple acyl-CoA Dehydrogenase Deficiency, results from a defect in the mitochondrial electron transport chain resulting in an inability to break down fatty-acids and amino acids. There are three phenotypes- type 1 and 2 are of neonatal onset and severe form, with and without congenital anomalies, respectively, and presents with acidosis, severe hypotonia, cardiomyopathy, hepatomegaly, and non-ketotic hypoglycemia. Type 3 or late-onset Multiple acyl-CoA Dehydrogenase Deficiency usually presents in the adolescent or adult age group with phenotype ranging from mild forms of myopathy and exercise intolerance to severe forms of acute metabolic decompensation on its chronic course. Type 3 Multiple acyl-CoA Dehydrogenase Deficiency rarely presents in infancy and in liver failure. We present a five-month-old developmentally normal female child with acute encephalopathy, hypotonia, non-ketotic hypoglycemia, metabolic acidosis, and liver failure, with a history of sibling death of suspected inborn error of metabolism. The blood acyl-carnitine levels in Tandem Mass Spectrometry and urinary organic acid analysis through Gas Chromatography–Mass Spectrometry were unremarkable. The patient initially responded to riboflavin, CoQ, and supportive management but ultimately succumbed to sepsis with shock and multi-organ dysfunction. The clinical exome sequencing reported a homozygous missense variation in exon 11 of the ETFDH gene (chr4:g.158706270C > T) that resulted in the amino acid substitution of Leucine for Proline at codon 456 (p.Pro456Leu) suggestive of Glutaric aciduria type IIc (OMIM#231,680).
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Abbreviations
- ETFA :
-
Electron Transfer Flavoprotein Alpha subunit
- ETFB :
-
Electron Transfer Flavoprotein Beta subunit
- ETFDH :
-
Electron Transfer Flavoprotein Coenzyme Q Oxidoreductase
- GCMS:
-
Gas Chromatography-Mass Spectrometry
- FAD:
-
Flavin Adenine Dinucleotide
- MADD:
-
Multiple acyl-CoA Dehydrogenase Deficiency
- TMS:
-
Tandem Mass Spectrometry
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Keshri, S., Goel, A.K., Johns, J. et al. “Liver Failure in an Infant of Late-Onset Glutaric Aciduria Type II”: Case Report. Ind J Clin Biochem 38, 545–549 (2023). https://doi.org/10.1007/s12291-021-01007-7
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DOI: https://doi.org/10.1007/s12291-021-01007-7