Poor tolerance of ketogenic diet for suspicion of PDH deficiency: What about another diagnosis?

Introduction: The ketogenic diet is a proposed treatment in PDH deficiency, favoring beta-oxidation as an energy source. Case report: We report a patient of 9 months whose state has rapidly degenerated as of 3 months of life: major hypotonia, absence of contact and hypertrophic cardiomyopathy. Cerebral MRI showed T2 hypersignal of the globus pallidus and hypomyelination. Lactate and pyruvate were increased (blood, CSF) with a ratio <20. PDH deficiency was evoked and confirmed by the decreased enzymatic activity. The blood CAA, urinary CAO, and plasma acylcarnitines profile were normal. The introduction of a ketogenic diet was immediately complicated by an acidocetosic coma without hyperlactatemia, with major ketones. The child improved rapidly after carbohydrate intake and hydration. The genetic study of PDH showed no anomaly. This outcome being unusual for a PDH primary deficiency, we tested a panel of genes of neurometabolic diseases, which revealed a homozygous mutation in the ECHS1 gene. Discussion: Short Chain Enoyl-CoA Hydratase (SCEH) deficiency (ECHS1 gene) induces a variable phenotype associating encephalopathy, epilepsy, deafness, optic atrophy, cardiomyopathy. SCEH catalyses the reversible hydration of methacrylyl-CoA (potentially toxic) in valine metabolism and the hydration of short hydroxyacyl-CoA chains in beta-oxidation. The accumulation of toxic products seems to be responsible for the secondary deficits observed such as PDH deficiency. Two cases of poor tolerance of ketogenic diet have been described, as in our patient. Conclusion: When a patient has a clinical and biological picture compatible with a primary PDH deficit, the poor tolerance of ketogenic diet should have you think of this rare cause of secondary deficit, the SCEH deficit.