Consensus Guidelines for Diagnosis and Management of Pyruvate Dehydrogenase Complex Deficiency

Pathogenic variants in genes encoding subunits or regulatory components of the pyruvate dehydrogenase complex

Primary pyruvate dehydrogenase complex deficiency comprises monogenic disorders whose spectrum ranges from early-onset congenital lactic acidosis to infantile or childhood global developmental delay with epilepsy, through to attenuated adult-onset neurological presentations. Given highly variable management across centres, reported by patients and advocacy groups, an international consortium of experts from Europe and North America (metabolic physicians, neurologists, dietitians, geneticists and patient representatives) undertook a structured literature review. The recommendations cover classification, recognition, diagnostic evaluation, dietary and non-dietary management, surveillance for complications, genetic counselling and transition to adult services. Each received a GRADE rating, and 199 recommendations reached consensus through a Delphi process. The work also identifies key evidence gaps and the need for disease-modifying therapies.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A long-awaited operational framework for a disease whose management varied from one centre to another, with a genetic counselling and adult transition section directly relevant to the genetics clinic. The level of evidence must be read recommendation by recommendation in the full text: the abstract does not detail the distribution of GRADE ratings, and the Delphi method formalizes expert consensus rather than producing evidence.

Analysis by Dr Thibaut Benquey