title: Recovery from neurological deficits following biotin treatment in a biotinidase Km variant.
abstract: A 15-year-old boy suffered from progressive bilateral optic neuropathy of acute onset at the age of 10 years. Subsequently he developed spastic paraparesis and a predominantly motor type neuro-axonal neuropathy in all limbs. The basic error has been elucidated to be due to an unusual biotinidase Km variant with biphasic enzyme kinetics causing systemic biotin depletion and consequent multiple biotin-dependent carboxylase deficiency. After daily oral substitution with 10 mg biotin metabolic derangements subsided rapidly. Follow-up studies over one year after substitution with biotin demonstrated remarkable recovery from part of the previously present neuro-ophthalmological, motor and cognitive deficits. The previously extinguished flash-evoked visual potentials now showed clear responses after six months of substitution with biotin. In contrast with reports in literature, these findings indicated that neurological damage associated with biotinidase deficiency, rather than being permanent, is to some extent reversible.
authors.affiliation: Department of Pediatrics, Ophthalmology and Psychological Medicine-Technical University of Aachen, Germany.
authors.forename: V T
authors.initials: VT
authors.lastname: Ramaekers
authors.forename: M
authors.initials: M
authors.lastname: Brab
authors.forename: G
authors.initials: G
authors.lastname: Rau
authors.forename: G
authors.initials: G
authors.lastname: Heimann
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000581:Amidohydrolases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D001710:Biotin / Q000008:administration & dosage / Q000627:therapeutic use*; D043523:Biotinidase; D001774:Blood Chemical Analysis; D003071:Cognition; D003124:Colorimetry; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009100:Multiple Carboxylase Deficiency / Q000097:blood / Q000378:metabolism; D009128:Muscle Spasticity / Q000175:diagnosis / Q000188:drug therapy; D009896:Optic Atrophy / Q000175:diagnosis / Q000188:drug therapy; D010243:Paralysis / Q000175:diagnosis / Q000188:drug therapy; D014786:Vision Disorders / Q000175:diagnosis; D014792:Visual Acuity
chemical_list: D001710:Biotin; D000581:Amidohydrolases; D043523:Biotinidase