Uridine-responsive epileptic encephalopathy: Precision treatment across the age spectrum - a case series.

INTRODUCTION

CAD deficiency (Type 50 early infantile epileptic encephalopathy) is a rare, yet treatable neurometabolic disorder characterised by refractory seizures, developmental delay, and dyserythropoietic anaemia. Timely recognition and treatment with uridine can dramatically alter the clinical course but remains challenging due to phenotypic variability and diagnostic limitations.

CASE PRESENTATIONS: We describe five patients with biallelic pathogenic CAD variants, presenting across the age spectrum from neonatal period to adulthood. Common features included pharmacoresistant epilepsy, developmental delay, cerebellar atrophy, and dyserythropoietic anaemia with blood smear showing anisopoikilocytosis. Diagnosis was confirmed through trio whole exome or genome sequencing. Initiation of uridine monophosphate (UMP) supplementation in 4 patients led to rapid seizure control, improved neurodevelopmental outcomes, and normalisation of blood counts. The remaining patient, who could not access UMP, died following progressive neurological deterioration.

CONCLUSIONS

CAD deficiency should be considered in patients with refractory epilepsy and unexplained anaemia. Early genetic diagnosis and initiation of uridine therapy can result in significant neurological and haematological improvement. Securing access to uridine is essential to improve outcomes in this otherwise devastating disorder.