Morphological erythrocyte abnormalities as potential biomarker of uridine-responsive epileptic encephalopathy

Abstract

Background

Uridine-responsive epileptic encephalopathy (developmental and epileptic encephalopathy-50: DEE-50) is a recently identified disorder caused by CAD gene variants. Although patients can be treated with oral uridine, early diagnosis remains challenging due to its diverse and non-specific clinical manifestations; therefore, biomarkers for early detection are awaited. We report a patient with DEE-50 presenting with progressive myoclonus epilepsy (PME) at age 12, in whom morphological abnormalities of erythrocytes, anisocytosis and poikilocytosis, were observed from an early stage despite normal hemoglobin levels.

Case presentation

The patient was a female in her 30s. At age 12, generalized tonic-clonic seizures repeatedly occurred. Examination revealed tremor, myoclonus, and ataxic gait. During the course, electroencephalography showed generalized polyspike discharges, leading to a diagnosis of PME. At the age of 14 years, she developed frequent seizures progressing to status epilepticus and became bedridden within two months. Despite a differential diagnosis, a definitive diagnosis could not be reached until age 30, when whole-exome sequencing revealed biallelic variants in the CAD gene, confirming DEE-50.

Discussion/conclusion

In this patient, structural abnormalities of erythrocytes were noted from an early stage without anemia. These abnormalities may serve as a potential biomarker for DEE-50.