Abstracts

Rationale: CAD related developmental and epileptic encephalopathy is an autosomal recessive neurodegenerative disorder caused by pathogenic variants in CAD gene that encodes a multifunctional enzyme involved in the initial steps of pyrimidine synthesis. This disorder was recently reported, and evidence suggests a positive response to treatment with oral uridine. In this report we demonstrated a successful treatment with oral uridine monophosphate in term of immediate cessation of seizures and improved quality of life.

Methods:
A retrospective chart review.
Case report:
Case 1 is a 6-year-old boy, presented with a mild delay in cognition, language, and motor function at three years of age. At age 3 years he had an onset of intractable seizure with multiple semiology. He had an episode of febrile status epilepticus (SE) at 3.5 years that led to prolonged hospitalization in ICU that included phenobarbitone coma and multiple antiseizure drugs (ASDs). He sustained hypoxic-ischemic insult and subsequently has undergone palliative epilepsy surgery to reduce the SE. He showed substantial deterioration and remained minimally conscious, nonverbal, encephalopathic and gastrostomy feeding dependent.

Case 2 is the older brother. He is currently 14 years old. He had delayed fine motor and language development, normal gross motor development and intellectual disability noticed at 3 years. Seizure began at three years with focal and generalized tonic clonic seizures several times a day and multiple ASDs did not reduce the seizure frequency. After a prolonged seizure, he exhibited unsteadiness, lack of coordination, could no longer walk independently, difficulty in speech, inattentiveness and plateaued in his development milestones. Physical examination showed normal growth, subnormal cognitive function with normal muscle tone, power and reflexes and no sensory deficit. He was noted to have right eye strabismus, dysmetria and dysarthria together with intension tremor and wide based gait.

Results: Blood smear indicated abnormal erythrocytes morphology without anemia.
EEG: Slow background activity, abundant generalized epileptic discharges, and generalized myoclonic seizures.
MRI brain showed cerebellar atrophy.
Exome sequencing identified a homozygous, novel and pathogenic variants c.5959C >G p.(Leu1987Val) in CAD gene in the two siblings.

Seizures were immediately and completely controlled upon starting uridine monophosphate 130 mg/k divided in 3 doses in patient 2. He had considerable progress in his functional skills at 7 months follow up. He can walk independently, run, ride his bicycle, and communicate with clear short sentences. Patient 1 showed partial seizures control and became more alert.

Conclusions: Whole exome has the potential to be a first-line diagnostic tool for a subset of infants/ children presenting with epileptic encephalopathy. We suggest to consider a short therapeutic trial of uridine monophosphate in patients presented with refractory epilepsy, acquired cerebellar atrophy not responding to ASDs and vitamins especially during infancy and early childhood

Funding: Please list any funding that was received in support of this abstract.: none.