Early Clinical Features of Late-Onset Profound Biotinidase Deficiency in 2 Adult Siblings

Biotinidase (BTD) deficiency is a treatable inborn error of metabolism associated with biallelic pathogenic variants in the BTD gene, causing reduced BTD activity and multiple carboxylase deficiency. Onset of neurocutaneous clinical features typically occurs in infancy or early childhood. BTD has been included on newborn screening because core symptoms can be prevented with timely initiation of biotin. A small number of individuals with profound BTD deficiency remain asymptomatic or have only mild symptoms until adolescence or adulthood when they develop severe neurologic complications that are not responsive to biotin. Early recognition of signs and symptoms of these patients is critical for effective treatment. We describe 2 adult siblings with late-onset profound BTD deficiency manifesting severe optic neuropathy and myelopathy that mimicked a demyelinating disorder. Transient vision impairment and mild symptoms of nonspecific neuropathy were documented in childhood.