A single infant with genetically confirmed non‑ketotic hyperglycinemia and biotinidase deficiency received a classic 3:1 ketogenic diet at 18 months. Within two weeks seizures decreased, and over the following year seizure burden was eliminated, several anti‑seizure drugs were withdrawn, and neurodevelopmental milestones were achieved.
Study and findings
The authors describe a female infant diagnosed with autosomal recessive glycine encephalopathy (non‑ketotic hyperglycinemia) and biotinidase deficiency through whole‑exome sequencing and enzyme assay. The child presented with neonatal‑onset focal seizures refractory to five anti‑seizure medications. At 18 months, a classic ketogenic diet with a 3:1 fat‑to‑combined protein‑carbohydrate ratio was initiated in a pediatric intensive care unit under multidisciplinary supervision. Within two weeks of diet initiation the patient showed marked clinical improvement. Over the next twelve months seizures were controlled, three anti‑seizure drugs were discontinued, nasogastric feeding was stopped, and the child attained meaningful neurodevelopmental milestones.
Clinical interpretation
In this case the ketogenic diet coincided with rapid seizure reduction and subsequent drug withdrawal, suggesting that ketosis may have mitigated the neurotoxic effects of accumulated glycine and the metabolic disturbance caused by biotinidase deficiency. The observed developmental gains imply that seizure control, together with improved metabolic stability, can translate into functional progress even in severe, drug‑resistant metabolic epilepsies. However, as a single‑patient observation, the report cannot establish causality; the improvement may also reflect natural disease evolution, concurrent supportive care, or other unmeasured factors.
Limitations and open questions
The evidence derives from a single case report without a control comparator, limiting generalizability to other patients with dual metabolic disorders. Details on dietary adherence, serum ketone levels, and quantitative seizure frequency are not provided, preventing assessment of dose‑response relationships. It remains unclear whether the ketogenic diet would be equally effective in patients with only one of the two disorders, or how timing of diet initiation influences outcomes. Prospective studies or registries collecting systematic data on ketogenic therapy in combined metabolic epilepsies are needed to clarify efficacy, optimal macronutrient ratios, and safety.
Source
Elbarky A, El Amrousy D, Mahmoud S, Lotfy A, Aboeisa M, Elballat KE, et al. Precision diagnosis guides ketogenic diet therapy in inherited metabolic epilepsies: Concurrent non-ketotic hyperglycinemia and biotinidase deficiency. Eur J Clin Nutr. 2026. doi: 10.1038/s41430-026-01821-3. PMID: 42760380.