摘要：Background We describe two adult brothers with lower limb neuropathy and one with progressive optic neuropathy. One brother was found to have profound biotinidase deficiency by identifying biallelic pathogenic variants of the BTD gene by whole exome sequencing, which was confirmed by markedly decreased serum biotinidase activity. Case report and methods The first brother had progressive optic atrophy and vision loss over 10 years and progressive peripheral neuropathy with weakness, pain, and fatigue for 20 years. Profound biotinidase deficiency was also identified in an older brother, who exhibited peripheral neuropathy since four years of age, but had no vision loss. Results The first brother's vision loss and neuropathy improved markedly with biotin in six months. However, the neuropathy of the other brother did not improve with 16 months of biotin therapy. Conclusions The first brother's neurological issues partially reversed with biotin. However, the longer-term symptoms of the other brother were irreversible. These cases emphasize the importance of considering biotinidase deficiency in the differential diagnosis of adolescents and adults with peripheral neuropathy with or without optic neuropathy/atrophy before symptoms become irreversible. Although WES initially identified the disorder in this family, measuring serum biotinidase activity was a necessary confirmatory step after WES and is less expensive than performing whole exome sequencing.
