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

• Published in: Journal of inherited metabolic disease 2017-03, Vol.40 (2), p.237-245
• Main Authors: Sofou, Kalliopi, Dahlin, Maria, Hallböök, Tove, Lindefeldt, Marie, Viggedal, Gerd, Darin, Niklas
• Format: Article
• Language: English
• Subjects: Adolescent; Biochemistry; Child; Child, Preschool; Cohort Studies; Diet, Ketogenic - methods; Epilepsy - blood; Epilepsy - diet therapy; Female; Human Genetics; Humans; Infant; Infant, Newborn; Internal Medicine; Ketone Bodies - blood; Ketosis - blood; Ketosis - diet therapy; Longitudinal Studies; Male; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Mental Status and Dementia Tests; Metabolic Diseases; Motor Activity - physiology; Original; Original Article; Pediatrics; Pediatrik; Pyruvate Dehydrogenase Complex Deficiency Disease - blood; Pyruvate Dehydrogenase Complex Deficiency Disease - diet therapy; Sweden; Treatment Outcome
• ISSN: 0141-8955; 1573-2665; 1573-2665
• DOI: 10.1007/s10545-016-0011-5

Objectives Our 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. Methods Pediatric 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. Results Nineteen 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. Conclusion Ketogenic 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.