Efficacy of ketogenic diet for pyruvate dehydrogenase complex deficiency

Chida, Rie; Shimura, Masaru; Nishimata, Shigeo; Kashiwagi, Yasuyo; Kawashima, Hisashi

doi:10.1111/ped.13700

Cited by 9 publications

(5 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In PDH DS, pyruvate conversion to acetyl-CoA is compromised, resulting in infantile lactic acidosis, seizure and neurodegeneration [36]. Pyruvate dehydrogenase is a multi-enzyme complex mediating pyruvate oxidative decarboxylation to acetyl-CoA.…”

Section: Clinical Relevance Of Ketogenic Dietmentioning

confidence: 99%

Ketogenic Diet: A New Light Shining on Old but Gold Biochemistry

et al. 2019

View full text Add to dashboard Cite

Diets low in carbohydrates and proteins and enriched in fat stimulate the hepatic synthesis of ketone bodies (KB). These molecules are used as alternative fuel for energy production in target tissues. The synthesis and utilization of KB are tightly regulated both at transcriptional and hormonal levels. The nuclear receptor peroxisome proliferator activated receptor α (PPARα), currently recognized as one of the master regulators of ketogenesis, integrates nutritional signals to the activation of transcriptional networks regulating fatty acid β-oxidation and ketogenesis. New factors, such as circadian rhythms and paracrine signals, are emerging as important aspects of this metabolic regulation. However, KB are currently considered not only as energy substrates but also as signaling molecules. β-hydroxybutyrate has been identified as class I histone deacetylase inhibitor, thus establishing a connection between products of hepatic lipid metabolism and epigenetics. Ketogenic diets (KD) are currently used to treat different forms of infantile epilepsy, also caused by genetic defects such as Glut1 and Pyruvate Dehydrogenase Deficiency Syndromes. However, several researchers are now focusing on the possibility to use KD in other diseases, such as cancer, neurological and metabolic disorders. Nonetheless, clear-cut evidence of the efficacy of KD in other disorders remains to be provided in order to suggest the adoption of such diets to metabolic-related pathologies.

show abstract

Section: Clinical Relevance Of Ketogenic Dietmentioning

confidence: 99%

Ketogenic Diet: A New Light Shining on Old but Gold Biochemistry

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The proband also demonstrated increased blood lactate with the increase of glucose infusion rate. This phenomenon has been known in PDH deficiency, and in fact, the patients with PDH deficiency responded to ketogenic diet 30,31 . Intralipid has been shown to improve acute rhabdomyolysis episodes 10 .…”

Section: Discussionmentioning

confidence: 94%

“…This phenomenon has been known in PDH deficiency, and in fact, the patients with PDH deficiency responded to ketogenic diet. 30 , 31 Intralipid has been shown to improve acute rhabdomyolysis episodes. 10 We demonstrated the use of parenteral nutrition containing high lipid and protein content to reverse acute rhabdomyolysis and lactic acidosis.…”

Section: Discussionmentioning

confidence: 99%

Clinical, biochemical and molecular characterization of a new case with FDX2‐related mitochondrial disorder: Potential biomarkers and treatment options

Wongkittichote,

Pantano,

et al. 2024

JIMD Reports

View full text Add to dashboard Cite

Ferredoxin‐2 (FDX2) is an electron transport protein required for iron–sulfur clusters biosynthesis. Pathogenic variants in FDX2 have been associated with autosomal recessive FDX2‐related disorder characterized by mitochondrial myopathy with or without optic atrophy and leukoencephalopathy. We described a new case harboring compound heterozygous variants in FDX2 who presented with recurrent rhabdomyolysis with severe episodes affecting respiratory muscle. Biochemical analysis of the patients revealed hyperexcretion of 2‐hydroxyadipic acid, along with previously reported biochemical abnormalities. The proband demonstrated increased lactate and creatine kinase (CK) with increased amount of glucose infusion. Lactate and CK drastically decreased when parenteral nutrition containing high protein and lipid contents with low glucose was initiated. Overall, we described a new case of FDX2‐related disorder and compare clinical, biochemical and molecular findings with previously reported cases. We demonstrated that 2‐hydroxyadipic acid biomarker could be used as an adjunct biomarker for FDX2‐related disorder and the use of parenteral nutrition as a treatment option for the patient with FDX2‐related disorder during rhabdomyolysis episode.Highlights2‐Hydroxyadipic acid can serve as a potential adjunct biomarker for iron‐sulfur assembly defects and lipoic acid biosynthesis disorders. Parenteral nutrition containing high lipid and protein content could be used to reverse acute rhabdomyolysis episodes in the patients with FDX2‐related disorder.

show abstract

“…An improvement in lactic acidosis as a clinical benefit of a ketogenic diet was first described more than four decades ago [ 4 ]. Increasingly, a ketogenic diet is being recognized as an effective therapy for epilepsy, delayed psychomotor development, sleep disturbance, and so on [ 2 , 3 , [5] , [6] , [7] , [8] , [9] ]. However, it has remained unknown how the ketogenic diet affects metabolism within the TCA cycle, which is the source of cellular energy production, and energetics in multiple organ systems.…”

Section: Introductionmentioning

confidence: 99%