Recommendations for the diagnosis and management of Niemann-Pick disease type C: An update

Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease caused by mutations in either the NPC1 (in 95% of cases) or the NPC2 gene (in around 5% of cases), which lead to impaired intracellular lipid trafficking and accumulation of cholesterol and glycosphingolipids in the brain and other tissues. Characteristic neurological manifestations of NP-C include saccadic eye movement (SEM) abnormalities or vertical supranuclear gaze palsy (VSGP), cerebellar signs (ataxia, dystonia/dysmetria, dysarthria and dysphagia) and gelastic cataplexy. Epileptic seizures are also common in affected patients. Typically, neurological disease onset occurs during childhood, although an increasing number of cases are being detected and diagnosed during adulthood based on late-onset neurological signs and psychiatric manifestations. Categorization of patients according to age at onset of neurological manifestations (i.e. early-infantile, late-infantile, juvenile and adolescent/adult-onset) can be useful for the evaluation of disease course and treatment responses. The first international guidelines for the clinical management of NP-C in children and adults were published in 2009. Since that time a significant amount of data regarding the epidemiology, detection/diagnosis, and treatment of NP-C has been published. Here, we report points of consensus among experts in the diagnosis and treatment of NP-C based on a follow-up meeting in Paris, France in September 2011. This article serves as an update to the original guidelines providing, among other things, further information on detection/diagnostic methods, potential new methods of monitoring disease progression, and therapy. Treatment goals and the application of disease-specific therapy with miglustat are also re-evaluated.