Pyruvate Dehydrogenase E3 Deficiency - Heterozygous Mutation in Dihydrolipoamide Dehydrogenase (DLD) Gene Associated with Symptomatic Hypoglycaemia. A Case Report

Abstract

Background: Pyruvate dehydrogenase complex deficiency (PDCD) is a mitochondrial disorder that presents with lactic acidemia and neurological manifestations. It is a very rare genetic disorder, a potentially life-threatening one with the usual presentation of hypotonia, lethargy, and developmental delay. It is commonly associated with structural brain abnormalities. We report a very rare case of transient severe symptomatic hypoglycaemia probably due to pyruvate dehydrogenase E3 deficiency; a component of pyruvate dehydrogenase complex (PDC). Case Presentation: Our patient is a 12-day-old neonate with lethargy, and vomiting presented with severe symptomatic hypoglycaemia with a critical sample suggestive of hyperinsulinism and raised lactate levels. A TMS-GCMS for metabolic abnormality screening was normal, however, a whole genome sequencing(nuclear + mitochondrial) revealed heterozygous missense variants (c.763A>C) in exon 9 of the DLD gene that results in the amino acid substitution from Methionine to Leucine at codon 255 (p.Met255Leu) and another heterozygous mutation of heterozygous missense variant (c.5277A>T) in exon 34 of the LAMB1 gene that results in the amino acid substitution from Glutamine to Histidine at codon 1759 (p.Gln1759His). Conclusion: There is no effective treatment for PDCD but reports of treatment with supplements like thiamine, biotin, and coenzyme Q may play a role in preventing the severity of the disease.