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

Area of Science:

• Genetics
• Neurology
• Metabolic Disorders

Background:

• CAD deficiency (Type 50 early infantile epileptic encephalopathy) is a rare, treatable neurometabolic disorder.
• Characterized by refractory seizures, developmental delay, and dyserythropoietic anemia.
• Timely recognition and uridine treatment can alter the clinical course, but diagnosis is challenging due to variable phenotypes and limitations.

Purpose of the Study:

• To describe clinical presentations and outcomes in patients with biallelic pathogenic CAD variants.
• To highlight the efficacy of uridine supplementation in managing CAD deficiency.
• To emphasize the importance of early genetic diagnosis and treatment access.

Main Methods:

• Described five patients with biallelic pathogenic CAD variants.
• Utilized trio whole exome or genome sequencing for diagnosis.
• Initiated uridine monophosphate (UMP) supplementation in four patients.

Main Results:

• Patients presented with pharmacoresistant epilepsy, developmental delay, cerebellar atrophy, and dyserythropoietic anemia.
• UMP supplementation led to rapid seizure control, improved neurodevelopment, and normalized blood counts.
• One patient who did not receive UMP experienced progressive neurological deterioration and died.

Conclusions:

• CAD deficiency should be considered in patients with refractory epilepsy and unexplained anemia.
• Early genetic diagnosis and uridine therapy significantly improve neurological and hematological outcomes.
• Ensuring access to uridine is crucial for improving patient outcomes in this disorder.