Pyruvate Dehydrogenase Complex Deficiency: A Review of Treatments and Case Series

TL;DR

This paper reviews treatment options for pyruvate dehydrogenase complex deficiency and presents case studies to explore their effectiveness.

Contribution

The paper provides a case series and literature review to evaluate treatment outcomes for PDCD, highlighting gaps in clinical research.

Findings

Dichloroacetate and ketogenic diet are the most studied treatments for PDCD.

Some treatments showed reduced lactate levels and improved neuropathological outcomes.

Most interventions lack rigorous investigation, emphasizing the need for clinical trials.

Abstract

Pyruvate dehydrogenase complex deficiency (PDCD) is a heterogenous mitochondrial inborn error in carbohydrate oxidation manifesting as congenital lactic acidosis. PDCD presents diagnostic and therapeutic challenges. While no curative treatment exists for PDCD, certain therapeutic modalities may improve prognosis and ameliorate symptom severity. This article examines the effectiveness of treatments for PDCD and presents a case series of three patients with PDCD. A scoping literature review was conducted for treatments of PDCD. Patient data for case reports was extracted retrospectively from electronic medical records from a large tertiary hospital. We reviewed and summarized findings from seven preclinical studies and ten human studies, which showed that dichloroacetate and the ketogenic diet were the most frequently studied treatments. Therapeutic approaches observed select positive outcomes such as reduced lactate levels, improved neuropathological manifestations, and increased longevity. However, most interventions have yet to be rigorously investigated. Early diagnosis of PDCD is integral, as treatment methods may offer improved clinical and biochemical outcomes. Clinical trials of existing and novel treatments are necessary to improve management and further understand the prognostic potential of this metabolic disorder.

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