Biotinidase deficiency mimicking neuromyelitis optica beginning at the age of 4: A treatable disease.

BACKGROUND: Metabolic and inflammatory conditions may lead to neurological disorders. Neuromyelitis optica spectrum disorders (NMOSDs) refer to a rare group of demyelinating diseases of the central nervous system which essentially involve the optic nerves and spinal cord. METHODS: We report a case of biotinidase deficiency (BD) initially misdiagnosed as NMOSD in a pediatric patient. RESULTS: An 8-year-old girl was initially diagnosed with NMOSD on the basis of optic neuritis (ON) associated with three episodes of longitudinally extensive transverse myelitis (LETM). Intravenous high-dose corticosteroids were effective during the first two episodes of LETM. The third acute episode which resulted in tetraplegia, respiratory distress, and blindness was refractory to corticosteroids, plasmapheresis, and rituximab. The unusual clinical course and persistent high levels of plasma and cerebrospinal fluid (CSF) lactate led to additional metabolic investigations being performed. Acylcarnitine profile revealed increased C5-OH acylcarnitine suggestive of BD. Diagnosis was confirmed by direct assessment of plasma enzyme activity (quantified as 5% of the control value). Genetic analysis revealed two mutations, c.643C>T (p.L215F) and c.1612C>T (p.R538C), in the BTD gene (3p25). Dramatic clinical improvement occurred after long-term oral biotin treatment. CONCLUSION: BD is a treatable condition that may closely mimic the neurological findings of LETM and NMOSD.

Effect of l-Arginine in One Patient with Peroxisome Biogenesis Disorder due to PEX12 Deficiency.

Peroxisome biogenesis disorders (PBD) are a heterogeneous group of disorders due to PEX genes mutations, with a broad clinical spectrum comprising severe neonatal disease to mild presentation. Recently, Berendse et al reported an improvement of peroxisomal functions with l-arginine supplementation in fibroblasts with specific mutations of PEX1, PEX6, and PEX12. We report the first treatment by l-arginine in a patient homozygous for the specific PEX12 mutation shown to be l-arginine responsive in fibroblasts. We described the effect of l-arginine on biochemical (decrease of some plasma peroxisomal parameters) and neurophysiological (improvement of deafness) parameters. Some subjective clinical effects have also been observed (no more sialorrhea, behavior improvement). More studies are needed to assess the efficacy of l-arginine in some PBD patients with specific mutations.