Pyruvate dehydrogenase deficiency: with more phenotypes than we think A case report

Abstract

Introduction: The pyruvate dehydrogenase complex (PDC) is a multienzyme complex responsible for catalyzing the oxidative decarboxylation of pyruvate to acetyl CoA. A defect in any of its components can interfere with energy production at the cellular level; within these disorders is pyruvate dehydrogenase (PDH) deficiency characterized by clinical neurological and systemic signs of variable severity, highlighting lactic acidosis, neurological and progressive neuromuscular deterioration.

Objective: To describe the case of a school patient with characteristic craniofacial dysmorphology, neurodevelopmental delay, and episodes of metabolic decompensation due to infections, with a mutation in the PDHX gene, managed with a ketogenic diet, thiamine, lipoic acid, and carnitine.

Results: The findings that made it possible to focus the diagnosis are elevated plasma and CSF lactate associated with persistent metabolic acidosis with accentuation of hyperintensity cortical sulci in the bilateral basal ganglion region and lenticular nuclei in brain resonance imaging, with magnetic resonance spectroscopy showing a negative peak of lactate. Confirming the diagnosis with an exome of 6000 genes where a homozygous pathogenic variant is found in the PDHX gene position c.1426C> T.

Conclusion: PDH deficiency should be considered in cases of neurodevelopmental delay associated with intermittent episodes of neurological deterioration and elevated blood lactate and in brain magnetic resonance spectroscopy. Unlike those affected by other subtypes, patients with E3-binding protein deficiency often survive childhood and even adulthood due to the presence of some assembly of the pyruvate dehydrogenase complex. Early diagnosis opens the possibility of starting supportive management, providing genetic counseling to parents, and prognosis and early support measures.