Screening for Biotinidase deficiency in children with spinal cord demyelination

Biotinidase deficiency (BD) is a disorder with autosomal recessive inheritance with protean clinical manifestations. Some cases present atypically with a neuroinflammatory phenotype that mimics neuromyelitis optica spectrum disorder. This can occur acutely in children who are otherwise normal leading to misdiagnosis and mismanagement with a potential for residual deficits.

To investigate biotinidase enzyme activity among children with presentation and radiological findings consistent with myelopathy.

This prospective observational study included children (≤18 years) admitted to the Pediatric Neurology Department, Ain Shams University Children's Hospital, with myelopathy and MRI evidence of spinal cord demyelination. Clinical, laboratory, ophthalmological, and neuroimaging data were systematically collected. Serum biotinidase enzyme activity was measured in all participants.

Thirty-nine children with spinal cord demyelination were included (44% male), with a median age at onset of 9 years. BD was identified in four patients. Presenting features included progressive limb weakness and gait disturbance, with optic neuropathy observed in three patients. Neuroimaging consistently demonstrated longitudinally extensive transverse myelitis involving the cervical and/or thoracic spinal cord, frequently accompanied by brainstem signal abnormalities. Prior to diagnosis, patients received immunomodulatory therapies with limited or transient benefit. Following biotin supplementation, all patients demonstrated clinical improvement, with residual deficits observed in those with delayed diagnosis.

BD should be considered in the differential diagnosis of pediatric spinal cord demyelination, particularly in antibody-negative cases or those with suboptimal response to immunotherapy. Further studies incorporating immune biomarkers are needed to determine whether adjunctive management of inflammation, alongside metabolic correction, may improve neurological outcomes.