Pyridoxal phosphate binding protein (PLPBP) deficiency mimicking opsoclonus-myoclonus-ataxia syndrome

Genetic and metabolic conditions can mimic diagnoses such as hypoxic-ischemic encephalopathy, meningoencephalitis, epilepsy, and opsoclonus-myoclonus-ataxia syndrome (OMAS). Without a high index of suspicion and proper testing, diagnoses can be missed, and treatment delayed.

A 3-year-old girl with a history of neonatal seizures and previous nondiagnostic epilepsy gene panel presented with seizures, behavioral changes, and discrete episodes of myoclonus, tremors, and abnormal eye movements following a viral illness.

Initial evaluation was concerning for OMAS, though metabolic causes remained on the differential. Metabolic testing revealed elevated glycine and glutamine, suggestive of a possible inborn error of metabolism. Whole exome sequencing demonstrated compound heterozygous variants in the PLPBP gene associated with pyridoxine-dependent epilepsy (PDE), consistent with her clinical presentation and leading to her diagnosis of PLPBP deficiency.

Clinicians should gauge the indications, advantages, and limitations of targeted sequencing panels versus whole exome sequencing. Continued evaluation is recommended in patients with a history of neonatal and infantile epilepsy, especially if they present with episodic crises related to viral illness even if prior genetic and metabolic investigations have been nondiagnostic. This report also highlights the clinical overlap between PLPBP deficiency and OMAS, and the differences in pathophysiology, treatment pathways, and implications.