Abstract
BackgroundNiemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. The signs and symptoms of NP-C vary with age at disease onset, and available therapies are directed at alleviating symptoms and stabilizing disease progression. We report the characteristics and factors related to disease progression, and analyze the effect of miglustat treatment on disease progression and patient survival using NP-C disability scales.MethodsThis retrospective, observational chart review included patients with NP-C from five expert NP-C centers. Patient disability scores were recorded using three published NP-C disability scales, and a unified disability scale was developed to allow comparison of data from each scale. Disease progression was represented by scores on the unified NP-C disability scale. Patients were stratified as infantile (< 4 years), juvenile (≥ 4 − < 16 years), and adult (≥ 16 years) based on age at diagnosis, and treated ≥1 year and non-treated/treated < 1 year based on the duration of miglustat treatment.ResultsThe analysis included 63 patients; the majority (61.9%) were on miglustat therapy for ≥1 year. Ataxia and clumsiness/frequent fall were the most common neurologic symptoms across age groups, whereas, hypotonia and delayed developmental milestones were specific to infantile patients. In both infantile and juvenile patients, visceral signs preceded diagnosis and neurologic signs were noted at or shortly after diagnosis. Adult patients presented with a range of visceral, neurologic, and psychiatric signs in years preceding diagnosis. Patients on miglustat therapy for ≥1 year had a lower mean annual disease progression compared with those untreated/treated < 1 year (1.32 vs 3.54 points/year). A significant reduction in annual disease progression in infantile patients, and a trend towards reduced disease progression in juvenile patients after ≥1 year of miglustat treatment, translated into higher age at last contact or death in these groups.ConclusionsThe type and onset of symptoms varied across age groups and were consistent with descriptions of NP-C within the literature. Miglustat treatment was associated with a reduced rate of disability score worsening in infantile and juvenile patients, both in agreement with increased age at last contact.
Highlights
Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology
Our primary objective was to analyze disease progression, represented by scores on a unified NP-C disability scale, in patients diagnosed with NP-C, to assess the effect of miglustat treatment over time for different clinical forms of NP-C defined by age of diagnosis
The pattern of onset of symptoms observed in this study is largely in agreement with the literature, where it is reported that patients who develop NP-C during early infancy often present with predominantly visceral manifestations followed by neurologic signs, whereas adolescent and adult patients present with varying combinations of progressive neurologic signs and psychiatric disturbances [3, 8, 19]
Summary
Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. Niemann-Pick disease Type C (NP-C) is a rare, fatal, autosomal recessive, lysosomal lipid storage disease characterized by progressive neurodegenerative symptomatology [1,2,3]. The age of onset of NP-C can range from the perinatal period to adulthood, with symptomatology varying with age of onset. Patients who develop NP-C during early infancy often present with visceral manifestations such as splenomegaly, hepatomegaly, and cholestasis, with varying degrees of neurologic signs and symptoms including delayed developmental milestones, hypotonia, and dystonia [8, 9]. Patients tend to present with varying combinations of progressive neurologic deficits such as ataxia, dystonia, and/or dementia or major psychiatric illness [9]. Vertical supranuclear saccade palsy/vertical supranuclear gaze palsy (VSGP) is the most common neurologic symptom, and is often overlooked during the initial differential diagnosis [3]
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