Title:Pyruvate Dehydrogenase E3 Deficiency - Heterozygous Mutation in
Dihydrolipoamide Dehydrogenase (DLD) Gene Associated with Symptomatic
Hypoglycaemia. A Case Report
Volume: 4
Author(s): Prashanth S. Veeraiah, Vikram S. Kumar, S R. Dhananjaya, Sajna Khalid and Shivaraj Gowda*
Affiliation:
- Xavier University, School of Medicine, Aruba, Dutch Caribbean & Subbaiah Institute of Medical Sciences, Shivamogga, Karnataka, India
Keywords:
Pyruvate dehydrogenase complex, Hyperinsulinism, Hypoglycaemia, Lactic acidosis, Hypotonia, Neonate.
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 presenting with lethargy, vomiting with severe symptomatic hypoglycaemia; 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.
