Ketogenic diet in pyruvate dehydrogenase complex deficiency: short- and long-term outcomes

ObjectivesOur aime was to study the short- and long-term effects of ketogenic diet on the disease course and disease-related outcomes in patients with pyruvate dehydrogenase complex deficiency, the metabolic factors implicated in treatment outcomes, and potential safety and compliance issues.MethodsPediatric patients diagnosed with pyruvate dehydrogenase complex deficiency in Sweden and treated with ketogenic diet were evaluated. Study assessments at specific time points included developmental and neurocognitive testing, patient log books, and investigator and parental questionnaires. A systematic literature review was also performed.ResultsNineteen patients were assessed, the majority having prenatal disease onset. Patients were treated with ketogenic diet for a median of 2.9 years. All patients alive at the time of data registration at a median age of 6 years. The treatment had a positive effect mainly in the areas of epilepsy, ataxia, sleep disturbance, speech/language development, social functioning, and frequency of hospitalizations. It was also safe—except in one patient who discontinued because of acute pancreatitis. The median plasma concentration of ketone bodies (3-hydroxybutyric acid) was 3.3 mmol/l. Poor dietary compliance was associated with relapsing ataxia and stagnation of motor and neurocognitive development. Results of neurocognitive testing are reported for 12 of 19 patients.ConclusionKetogenic diet was an effective and safe treatment for the majority of patients. Treatment effect was mainly determined by disease phenotype and attainment and maintenance of ketosis.

• Publication year

  2017

• Venue

  Journal of Inherited Metabolic Disease

• Publication date

  2017-01-18

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1007/s10545-016-0011-5PMID 28101805PMCID 5306430
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Effectiveness of the ketogenic diet used to treat resistant childhood epilepsy in Scandinavia.

  2015cited by this paper
• Ketogenic diets in patients with inherited metabolic disorders

  2015cited by this paper
• Pyruvate dehydrogenase-e1α deficiency presenting as recurrent demyelination: an unusual presentation and a novel mutation.

  2013cited by this paper
• Mild Phenotype in a Male with Pyruvate Dehydrogenase Complex Deficiency Associated with Novel Hemizygous In-Frame Duplication of the E1α Subunit Gene (PDHA1)

  2013cited by this paper
• The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients.

  2012cited by this paper
• Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: lack of correlation with genotype.

  2012influential reference
• Case Report of Pyruvate Dehydrogenase Deficiency With Unusual Increase of Fats During Ketogenic Diet Treatment

  2012cited by this paper
• Unilateral periventricular leukomalacia in association with pyruvate dehydrogenase deficiency

  2012cited by this paper
• The effects of the ketogenic diet on behavior and cognition.

  2012cited by this paper
• Pyruvate dehydrogenase deficiency and epilepsy.

  2011cited by this paper
• Follow-up of a child with pyruvate dehydrogenase deficiency on a less restrictive ketogenic diet.

  2011cited by this paper
• Pyruvate dehydrogenase complex deficiency: four neurological phenotypes with differing pathogenesis

  2010cited by this paper
• Pyruvate dehydrogenase E2 deficiency: a potentially treatable cause of episodic dystonia.

  2010cited by this paper
• Ketogenic Diet Improves Sleep Quality in Children with Therapy‐resistant Epilepsy

  2007cited by this paper
• Nonspecific mitochondrial disease with epilepsy in children: diagnostic approaches and epileptic phenotypes

  2007cited by this paper
• Monocarboxylate transporters in the central nervous system: distribution, regulation and function

  2005cited by this paper
• Pyruvate dehydrogenase E1alpha subunit deficiency in a female patient: evidence of antenatal origin of brain damage and possible etiology of infantile spasms.

  2004cited by this paper
• Effects of ketogenic diet on development and behavior: preliminary report of a prospective study.

  2001cited by this paper
• Experience with the ketogenic diet in infants.

  2001cited by this paper
• Outcome of pyruvate dehydrogenase deficiency treated with ketogenic diets

  1997cited by this paper
• Leigh syndrome associated with a deficiency of the pyruvate dehydrogenase complex: results of treatment with a ketogenic diet.

  1992cited by this paper
• Defective gene in lactic acidosis: abnormal pyruvate dehydrogenase E1 alpha-subunit caused by a frame shift.

  1989cited by this paper
• Variable clinical presentation in patients with defective E1 component of pyruvate dehydrogenase complex.

  1987cited by this paper
• Sensitivity to Carbohydrate in a Patient with Familial Intermittent Lactic Acidosis and Pyruvate Dehydrogenase Deficiency

  1976cited by this paper
• Ketonic diet in the management of pyruvate dehydrogenase deficiency.

  1976cited by this paper
• Multienzyme complexes.

  1966cited by this paper

• Lactate Metabolism in Health and Disease.

  2025cites this paper
• Therapies for Mitochondrial Disease: Past, Present, and Future

  2025cites this paper
• Metabolic plasticity: an evolutionary perspective on metabolic and circadian dysregulation in bipolar disorder

  2025cites this paper
• Mitochondrial cardiomyopathies: pathogenesis, diagnosis, and treatment.

  2025cites this paper
• Rare Movement Disorders—An Approach for Clinicians

  2025cites this paper
• Outcomes of Ketogenic Diet in Pediatric Intractable Epilepsy and Neurometabolic Disorders: Insights From the First Iranian Registry.

  2025cites this paper
• Exploring inherited vitamin B responsive disorders in the Moroccan population: cutting-edge diagnosis via GC-MS profiling

  2025cites this paper
• Genetic aetiologies in relation to response to the ketogenic diet in 226 children with epilepsy

  2025cites this paper
• Clinical and biochemical footprints of inherited metabolic diseases: Ia. Movement disorders, updated.

  2025cites this paper
• Clinical Efficacy and Safety of the Ketogenic Diet in Patients with Genetic Confirmation of Drug-Resistant Epilepsy

  2025cites this paper
• From Severe Neonatal Encephalopathy to Slowly Neurologic Progressive Disease: Pyruvate Dehydrogenase Deficiency Related to PDHA1 Variants.

  2025cites this paper
• Ketogene Diät bei pharmakoresistenter Epilepsie

  2025cites this paper
• Genetic and Epigenetic Modifiers of Ketogenic Diet Responses: Roles of Sex and Age

  2025cites this paper
• Efficacy and safety of ketogenic diets in drug-resistant epilepsy: a systematic review and meta-analysis

  2025cites this paper
• Mitochondrial Leigh syndrome: the state of the art.

  2025cites this paper
• Dietary Therapy in the Management of Epilepsy

  2025cites this paper
• Carotid intima‐media thickness may be an early biomarker for cardiovascular risk in patients treated with ketogenic dietary therapy

  2025cites this paper
• Ketogenic diet in neonates: effects, pitfalls, and a paradigm from a preterm newborn affected by pyruvate dehydrogenase deficiency.

  2025cites this paper
• Biomarkers of mitochondrial dysfunction in autism spectrum disorder: A systematic review and meta-analysis.

  2024cites this paper
• Emerging therapies for childhood-onset movement disorders

  2024cites this paper
• Manifestations of X‐linked pyruvate dehydrogenase complex deficiency in female PDHA1 carriers

  2024cites this paper
• Ketogenic Diet Interventions in Inborn Errors of Metabolism: A Review Article

  2024cites this paper
• Efficacy and Safety of Ketogenic Diet Treatment in Pediatric Patients with Mitochondrial Disease

  2024cites this paper
• [Fourteenth Jesús Culebras Lecture. Ketogenic diet, a half-discovered treatment].

  2024cites this paper
• Advancing the neuroimaging diagnosis and understanding of mitochondrial disorders

  2024cites this paper
• Lactic Acidosis in a Neonate with Ventriculomegaly and Hypoplasia of the Corpus Callosum.

  2024cites this paper
• Clinical, biochemical and molecular characterization of a new case with FDX2 ‐related mitochondrial disorder: Potential biomarkers and treatment options

  2024cites this paper
• Ketogene Ernährungstherapie

  2024cites this paper
• Mitochondrial disorder diagnosis and management- what the pediatric neurologist wants to know.

  2024cites this paper
• Ketogenic diet therapy for the treatment of pediatric epilepsy

  2024influential citation
• An integrated multi-omics approach allowed ultra-rapid diagnosis of a deep intronic pathogenic variant in PDHX and precision treatment in a neonate critically ill with lactic acidosis.

  2024cites this paper
• Classic ketogenic diet-induced ketoacidosis in the treatment of pyruvate dehydrogenase deficiency: a case report and literature review

  2024influential citation
• A Comprehensive Approach to the Diagnosis of Leigh Syndrome Spectrum

  2024cites this paper
• Mitochondrial ataxia - Unravelling the puzzle

  2024cites this paper
• Categorizing Monogenic Epilepsies by Genetic Mechanisms May Predict Efficacy of the Ketogenic Diet.

  2024cites this paper
• Prenatal molecular diagnosis of pyruvate dehydrogenase complex deficiency enables rapid initiation of ketogenic diet

  2024influential citation
• Ketogenic Diet and Progression of Kidney Disease in Animal Models of Nephropathic Cystinosis

  2024cites this paper
• Pyruvate dehydrogenase deficiency in a boy: a clinical case

  2024cites this paper
• Ketogenic Diet plus Resistance Training Applied to Physio-Pathological Conditions: A Brief Review

  2024cites this paper
• Long-term use of investigational β-Hydroxybutyrate salts in children with multiple acyl-CoA dehydrogenase or pyruvate dehydrogenase deficiency

  2024cites this paper
• Characterization of β-Hydroxybutyrate as a Cell Autonomous Fuel for Active Excitatory and Inhibitory Neurons

  2024cites this paper
• Potential therapeutic effect of a ketogenic diet for the treatment of lymphoedema: Results of an exploratory study.

  2024cites this paper
• Imaging brain glucose metabolism in vivo reveals propionate as a major anaplerotic substrate in pyruvate dehydrogenase deficiency.

  2024cites this paper
• The use of ketogenic diets in children living with drug-resistant epilepsy, glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency: A scoping review.

  2024cites this paper
• Pyruvate dehydrogenase complex deficiency masked by septic shock-induced lactic acidosis: a case report

  2024cites this paper
• Effect of inhibiting PDHα1 gene expression on the metabolism of fatty liver cells

  2024cites this paper
• Leigh syndrome.

  2023cites this paper
• Evaluating the efficacy of a ketogenic diet in managing drug resistant paediatric DEDPC5-related epilepsy.

  2023cites this paper
• Nutritional Approach in Selected Inherited Metabolic Cardiac Disorders—A Concise Summary of Available Scientific Evidence

  2023cites this paper
• The effects of ketogenic dietary therapies on sleep: A scoping review

  2023cites this paper
• Acute Flaccid Paralysis due to Pyruvate Dehydrogenase E1-Alpha Deficiency

  2023cites this paper
• Optimized Nutrition in Mitochondrial Disease Correlates to Improved Muscle Fatigue, Strength, and Quality of Life

  2023cites this paper
• Amino acid ratio combinations as biomarkers for discriminating patients with pyruvate dehydrogenase complex deficiency from other inborn errors of metabolism

  2023influential citation
• The Influence of Ketogenic Diet on Gut Microbiota: Potential Benefits, Risks and Indications

  2023cites this paper
• Mitochondrial encephalomyopathy.

  2023cites this paper
• Sandwich-Associated Lactic Acidosis: A Case Report of a Young Adult With Pyruvate Dehydrogenase Complex Deficiency

  2023cites this paper
• A Review of Ketogenic Dietary Therapies for Epilepsy and Neurological Diseases: A Proposal to Implement an Adapted Model to Include Healthy Mediterranean Products

  2023cites this paper
• Ketogenic Diet in Children and Adolescents: the Effects on Growth and Nutritional Status.

  2023cites this paper
• Ketogenic diet in action: Metabolic profiling of pyruvate dehydrogenase deficiency

  2023cites this paper
• The pyruvate dehydrogenase complex: Life's essential, vulnerable and druggable energy homeostat.

  2023cites this paper
• Pediatric Epilepsy Treatment

  2022cites this paper
• Dietary Treatments for Epilepsy.

  2022cites this paper
• Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier

  2022cites this paper
• Rare metabolic disease mimicking COL4A1/COL4A2 fetal brain phenotype

  2022cites this paper
• Functional Vitamin B2 Deficiency in Autism

  2022cites this paper
• A Mixed-Lipid Diet (Medium-Chain and Long-Chain Triglycerides) for Better Tolerability and Efficiency in Pediatric Epilepsy Patients

  2022cites this paper
• Population-based, cross-sectional assessment of dietary patterns and supplement use in mitochondrial disease.

  2022cites this paper
• AAV-vector based gene therapy for mitochondrial disease: progress and future perspectives

  2022cites this paper
• Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency

  2022influential citation
• Neurogenetic and Metabolic Mimics of Common Neonatal Neurological Disorders.

  2022cites this paper
• The Influence of Ketone Bodies on Circadian Processes Regarding Appetite, Sleep and Hormone Release: A Systematic Review of the Literature

  2022cites this paper
• Leigh Syndrome: A Study of 209 Patients at the Beijing Children's Hospital

  2022cites this paper
• The use of a low carbohydrate, ketogenic diet in bipolar disorder: systematic review

  2021influential citation
• Novel presentations associated with a PDHA1 variant - Alternating hemiplegia in Hemizygote proband and Guillain Barre Syndrome in Heterozygote mother.

  2021cites this paper
• The utility of next-generation sequencing technologies in diagnosis of Mendelian mitochondrial diseases and reflections on clinical spectrum

  2021cites this paper
• A Concise Review of Ketogenic Dietary Interventions in the Management of Rare Diseases

  2021cites this paper
• Current and Emerging Clinical Treatment in Mitochondrial Disease

  2021cites this paper
• Clinical exome sequencing reveals a mutation in PDHA1 in Leigh syndrome: A case of a Chinese boy with lethal neuropathy

  2021cites this paper
• Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app

  2021cites this paper
• The first case of FBXL4 mutation successfully treated with a parenteral ketogenic diet for lactic acidosis.

  2021cites this paper
• Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments

  2021cites this paper
• Митохондриальная энцефаломиопатия, обусловленная недостаточностью пируватдегидрогеназного комплекса: восемь клинических случаев

  2021cites this paper
• REVIEW: Practical strategies to maintain anabolism by intravenous nutritional management in children with inborn metabolic diseases.

  2021cites this paper
• Genetic and Metabolic Neonatal Epilepsies.

  2021cites this paper
• Ketogenic diet for mitochondrial disease: a systematic review on efficacy and safety

  2021influential citation
• Emerging Role of the Ketogenic Dietary Therapies beyond Epilepsy in Child Neurology

  2021cites this paper
• Recent aspects of ketogenic diet in neurological disorders

  2021cites this paper
• Recurrent acute pancreatitis during a ketogenic diet—a case report and literature review

  2021cites this paper
• The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency

  2021influential citation
• Long-term effectiveness and adverse effects of ketogenic diet therapy in infants with drug-resistant epilepsy treated at a single center in Argentina.

  2021cites this paper
• Efficacy and tolerability of the modified Atkins diet in children with drug-resistant genetic generalized epilepsy.

  2021cites this paper
• Intravenous ketogenic diet therapy for neonatal-onset pyruvate dehydrogenase complex deficiency.

  2021cites this paper
• Novel imaging findings in pyruvate dehydrogenase complex (PDHc) deficiency—Results from a nationwide population‐based study

  2021cites this paper
• Disorders of Carbohydrate Metabolism

  2021cites this paper
• Utility of specific amino acid ratios in screening for pyruvate dehydrogenase complex deficiencies and other mitochondrial disorders associated with congenital lactic acidosis and newborn screening prospects

  2020cites this paper
• Triheptanoin in Pyruvate Dehydrogenase Deficiency

  2020cites this paper
• Measurement of genetic diseases as a cause of mortality in infants receiving whole genome sequencing

  2020cites this paper
• Potential role of stress-induced gluconeogenesis in disease aggravation and mortality in pyruvate dehydrogenase deficiency: A case-based hypothesis.

  2020cites this paper
• Intérêts et limites de la diète cétogène

  2020cites this paper
• Medication-Resistant Epilepsy

  2020cites this paper