A Case of Vitamin-B6-Dependent Disorder Presenting with Abnormal Eye–Head Movements and Infantile Spasms without Hypsarrhythmia

Objectives: Infantile spasm without hypsarrhythmia is a rare electroclinical entity of heterogeneous etiology. A new vitamin-B6-dependent epilepsy of usually neonatal or very early onset (before 3 months) has been recently described and related to mutations in PLPBP, encoding for PLP-protein which has been proposed to be related to intracellular PLP-homeostasis.

Content: We report on an 8-month-old girl who presented at the age of 4 months with paroxysmal episodes of abnormal multidirectional eye–head movements followed by almost daily epileptic spasms at 5 months of age. She was known for mild-to-moderate gastroesophageal reflux. No developmental plateauing or regression was observed. Repeated prolonged EEG recordings showed normal background activity during wakefulness and sleep, rare and isolated frontal sharp waves. Bifrontal epileptiform discharges were consistently associated to the epileptic spasms. The initial presentation with paroxysmal episodes of abnormal eye–head movements with early-onset epilepsy led to the primary differential diagnosis of Glut1-deficiency syndrome. Metabolic testing including Glut1-deficiency syndrome and plasma vitamin B6 profile screening was negative. The girl responded dramatically to treatment with pyridoxine, becoming seizure free after the first dose, and gastroesophageal reflux was resolved. Whole-exome sequencing revealed compound heterozygous mutations in PLPBP.

Conclusion: This case further supports the heterogeneous phenotype of vitamin-B6-dependent epilepsies and presents a novel associated phenotype with infantile spasms without hypsarrhythmia. Metabolic screening for classical vitamin-B6 metabolism disorders is negative in PLPBP-related disorders. Index of suspicion should be high in early-onset epilepsies also after the age of 3 months as dramatic response to treatment with pyridoxine or PLP may be seen.

Publikationsverlauf

Artikel online veröffentlicht:
16. März 2022