Juvenile Optikoneuropathie durch Km-Variante der Biotinidase

A patient with a newly recognised variant of biotinidase deficiency presented with acute bilateral visual loss at the age of 10 years. A progressive optic neuropathy, a predominantly motor type neuropathy and spastic paraparesis developed over the following 5 years. Metabolic investigations revealed biotin depletion causing multiple biotin dependent carboxylase deficiency. The basic defect was a biotin recycling disorder due to a biotinidase Km variant with residual colorimetric activity of 4.4% of normal. Further investigations on plasma biotinidase showed biphasic kinetics with two different reduced Vmax values and two Km-values, one being almost normal and the other highly elevated. After a period of 2 months of oral substitution with biotin 10 mg per day the visual field defects improved as well as the distal spastic parapareses and motor neuropathy. We conclude that the differential diagnosis of unexplained bilateral optic neuropathy of juvenile onset, particularly when associated with upper and lower motor neuron disease should include biotinidase deficiency.