Classic ketogenic diet-induced ketoacidosis in the treatment of pyruvate dehydrogenase deficiency: a case report and literature review

Abstract

Background: As a rare mitochondrial disorder, the pyruvate dehydrogenase complex (PDC) deficiency is a rare inborn disease characterized with glucose metabolism defects, which leads to neurological dysfunction, serum lactic acid buildup and a resultant trend of metabolic acidosis. Although the ketogenic diet (KD) is the first-line treatment for PDC deficiency, there is currently no widely accepted consensus on specific implementation of KD for this condition. Due to the combined effect of pre-existing hyperlactacidemia and KD-induced ketoacidosis that can further exacerbate metabolic disturbances, maintaining metabolic homeostasis should be prioritized during the implementation of KD.

Case presentation: Herein, the authors present a 6-year-old boy with lactic acidosis, ataxia, hypotonia and neuromotor development retardation. The KD was started after the patient was diagnosed with PDC deficiency based on genetic testing. The initiation with classic KD resulted in severe non-diabetic ketoacidosis with elevated anion gap, which was promptly alleviated by dextrose supplementation and dietary modification to a less-restrictive KD. Long-term supervision demonstrated the efficacy of a modified KD in improving both clinical course and metabolic acidosis of the patient.

Conclusions: This rare case adds to the limited evidence of KD application in PDC deficiency, and provides valuable insights into the importance of reasonably lowering the ketogenic ratio of KD at the start of treatment to reduce the risk of metabolic acidosis.

Keywords: Acidosis; Ketogenic diet; Lactic acid; Non-diabetic ketoacidosis; Pyruvate dehydrogenase complex deficiency.

Fig. 1

Brain magnetic resonance imaging of the patient showed bilateral T2 hyperintensities of the globus pallidus, and lesions in periventricular tissue and left subfrontal cortex

Fig. 2

The specific regimen of the ketogenic diet intervention. (A) The intervention initiation with a classic ketogenic diet (with a ketogenic ratio of 3 ∼ 4:1) providing 1400 kcal/d. (B) The subsequent change to a modified Atkins diet (with the ketogenic ratio of 0.8-1: 1) providing 1400 kcal/d

Fig. 3

Change of the ABG following the KD implementation. A decease in pH, cHCO3, BE and an elevation in AG was associated with the classic KD initiation in 5 days; the metabolic acidosis was ameliorated promptly by small amount of glucose intake and a long-term remission of the metabolic disturbance was maintained subsequently on modified Atkins diet with or without MCT replacement