Late onset biotinidase deficiency presenting with optic neuropathy and multifocal motor neuropathy phenotype: a case report and literature review

Abstract

Biotinidase deficiency (BTD) is a rare, autosomal recessive neurometabolic disorder that is highly treatable but frequently underdiagnosed, particularly in its late-onset form. It may present with atypical neurological manifestations mimicking inflammatory, hereditary, or neurodegenerative conditions. We report a 15-year-old Omani male, born to consanguineous parents, who presented with progressive bilateral painless visual loss over 6 weeks. Neuro-ophthalmological evaluation revealed severe optic neuropathy with absent visual evoked potentials and ganglion cell complex thinning, despite preserved optic disc appearance. Magnetic resonance imaging was unremarkable except for an incidental cervical syrinx. Autoimmune and inflammatory workup, including AQP4 and MOG antibodies, was negative. Whole-exome sequencing identified double homozygous pathogenic variants in the BTD gene, and enzymatic testing confirmed profound biotinidase deficiency. During evaluation, the patient developed subacute distal limb weakness with electrophysiological findings fulfilling diagnostic criteria for multifocal motor neuropathy (MMN), including conduction block with preserved sensory responses. He was treated with high-dose oral biotin and intravenous immunoglobulin (IVIG), resulting in early visual and motor improvement. This case highlights late-onset BTD as a diagnostic mimic of Leber hereditary optic neuropathy, neuromyelitis optica spectrum disorder, and MMN. The presence of conduction block neuropathy expands the phenotypic spectrum of BTD. Early recognition is critical, as prompt biotin therapy may lead to neurological improvement. BTD should be considered in unexplained optic neuropathy with multisystem involvement, particularly in consanguineous populations.