Abstract
Non-ketotic hyperglycinemia (NKH) and biotinidase deficiency are rare inborn errors of metabolism that individually predispose to severe, drug-resistant epilepsy. Their concurrent occurrence in a single patient represents an exceptionally uncommon diagnostic and therapeutic challenge. The ketogenic diet (KD) has emerged as an adjuvant effective intervention in metabolic epilepsies, yet its role in dual metabolic disorders of this nature has not been previously described. We report female infant with autosomal recessive glycine encephalopathy (NKH) and biotinidase deficiency confirmed by whole exome sequencing and enzyme assay, who presented with neonatal-onset focal seizures and progressive encephalopathy refractory to five anti-seizure medications (ASMs). Initiation of classic 3:1 KD occurred during a PICU admission supervised by a multidisciplinary team (MDT) at 18 months of age. Within two weeks, significant clinical improvement was observed. Over the subsequent year, seizures were controlled, three ASMs were successfully withdrawn, encephalopathy episodes were eliminated, nasogastric tube feeding was discontinued, and the patient achieved meaningful neurodevelopmental milestones. This case highlights the potential of the KD as a unified therapeutic approach to improve clinical outcomes in patients with co-existing NKH and biotinidase deficiency. Early implementation of KD under the guidance of MDT may interrupt the neurotoxic cascade of glycine accumulation and biotin-dependent metabolic dysfunction, enhancing seizure control, development and quality of life.