Niemann-Pick disease type C is a rare inherited
cholesterol trafficking disorder, where impaired intracellular
lipid transport leads to storage of unesterified
cholesterol and
glycosphingolipids in many tissues, including the brain. Substrate reduction
therapy with
miglustat, an iminosugar that inhibits
glycosphingolipid synthesis, was proposed to treat
Niemann-Pick disease type C, based on evidence of slower
disease progression and prolonged survival in animal models.
Miglustat was subsequently approved in Europe to treat progressive
neurologic manifestations in both children and adults in early 2009, based on clinical study data. We report on the early treatment of two pediatric Niemann-Pick type C patients with
miglustat. Patient 1, a 7.5-year-old girl with early-infantile onset, began receiving
miglustat at age 7 months. Patient 2, the brother of a girl diagnosed with late-infantile onset Niemann-Pick type C, began receiving
miglustat at age 19 months, when he was asymptomatic for neurologic disease. After 7 and 5 years of
miglustat therapy, respectively, both patients remain free of
neurologic manifestations. These findings suggest that
miglustat may be more effective if used to prevent, rather than treat,
neurologic manifestations in infantile-onset Niemann-Pick type C.