Natural history of Niemann-Pick disease type C in a multicentre observational retrospective cohort study
Journal
Molecular Genetics and Metabolism
Journal Volume
98
Journal Issue
3
Pages
250-254
Date Issued
2009
Author(s)
Abstract
Niemann-Pick disease type C (NP-C) is a devastating genetic disorder characterised by progressive neurological deterioration. However, data on the progression of neurological manifestations, particularly across different patient age-of-disease onsets, are limited. This is an observational retrospective cohort study designed to assess the progression of neurological disease in patients with NP-C. Physicians were asked to retrospectively complete a web-based questionnaire for each patient, at diagnosis and at up to three follow-up visits. An NP-C-specific disability scale was used to measure disease progression. The scale comprised four key parameters of neurological disease progression; ambulation, manipulation, language and swallowing. Disease progression was evaluated based on the annual rate of change in each parameter and the composite score using a linear mixed model analysis, and by classifying patients according to the number of worsened parameters during the observation period. Data were collected from 57 patients. The rate of deterioration was similar across the four individual parameters of the disability scale. The mean (95% CI) annual disease progression was +0.12 (0.09, 0.15) units. Among patients with a time interval of at least 1 year between diagnosis and last visit (n = 49), 42 (86%) patients had progressed disease and 7 (14%) patients had stable disease. Disease progression was consistently more rapid in patients diagnosed in early childhood, compared with those diagnosed in late childhood, or with juvenile or adult presentation. In conclusion, our findings showed a progression in all four parameters of the disability scale, representing a continuous, unbroken progression of neurological manifestations. ? 2009 Elsevier Inc. All rights reserved.
Subjects
Disease progression; Natural history; Niemann-Pick disease type C; NP-C
Other Subjects
adolescent; adult; analytical parameters; article; child; childhood; clinical assessment; cohort analysis; disability; disease course; disease severity; female; follow up; human; language; major clinical study; male; mobilization; Niemann Pick disease; observational study; onset age; physician; preschool child; priority journal; questionnaire; rating scale; retrospective study; school child; swallowing; Adolescent; Child; Child, Preschool; Cohort Studies; Disability Evaluation; Disease Progression; Female; Humans; Male; Niemann-Pick Disease, Type C; Retrospective Studies
Type
journal article