Benefits and adverse effects of ketogenic diet treatment in pediatric patients with inborn errors of metabolism

BACKGROUND: The ketogenic diet (KD) is an established therapeutic option for epilepsy and selected inborn errors of metabolism (IEMs), particularly glucose transporter type 1 deficiency (GLUT1D) and pyruvate dehydrogenase complex deficiency (PDCD). Increasing evidence suggests broader applications of KD in pediatric metabolic disorders; however, data on its safety and efficacy in heterogeneous IEM populations remain limited. OBJECTIVES: To evaluate the efficacy, clinical benefits, and adverse effects (AEs) of KD in pediatric patients with various IEMs. MATERIAL AND METHODS: A retrospective analysis was conducted in pediatric patients with IEMs receiving KD treatment. Patients were categorized into 3 groups: 1) other IEMs (n = 7), 2) mitochondrial diseases (MD) (n = 17), and 3) GLUT1D and PDCD (n = 20). The median age at initiation of KD was 37, 53, and 53 months, respectively, and the median duration of KD treatment was 5, 11, and 55 months in groups 1, 2, and 3. RESULTS: The KD was associated with clinical benefits in 84% of patients. Among children with epilepsy (n = 23), a seizure reduction of >50% was observed in 73.9% of patients, including complete seizure freedom in 4 individuals. Improvements were also noted in muscle tone (27.6%), exercise tolerance (51.2%), ataxia (83.3%), and involuntary movements (60%). Lactate levels decreased in 84.6% of patients with mitochondrial disease and in all patients with PDCD. The KD was discontinued in 12 patients due to insufficient efficacy (n = 5) or AEs (AEs; n = 7). The most common AEs included gastrointestinal (GI) symptoms, dyslipidemia, hyperuricemia, metabolic acidosis, and decreased free carnitine; most were transient. No significant association was found between median β-hydroxybutyrate (BHB) levels and clinical outcomes. CONCLUSIONS: The KD is an effective and generally well-tolerated therapeutic option in pediatric IEMs, with benefits extending beyond seizure control. Adverse effects are typically manageable, although GI intolerance may limit long-term use. Ketogenic diet should be considered not only for refractory epilepsy but also for selected metabolic indications.