Clinical disease characteristics of patients with NiemannPick Disease Type C: Findings from the International Niemann-Pick Disease Registry (INPDR)

Orphanet J Rare Dis. 2022 Feb 14;17(1):51. doi: 10.1186/s13023-022-02200-4.

PMID: 35164809

Shaun C Bolton, Vina Soran, Mercedes Pineda Marfa

Highlights: The collection of on-going large-scale Niemann-Pick Disease Type C (NPC) clinical data may generate better understandings of the natural history of the disease. This study reports NPC patient data from the International Niemann-Pick Disease Registry (INPDR).

Abstract

Background: The autosomal recessive rare disease Niemann-Pick Disease Type C (NPC) is characterized by progressive neurovisceral symptoms. The ongoing collecting of large-scale NPC clinical data could lead to a better understanding of the disease's natural history. The data about NPC patients from the International Niemann-Pick Disease Registry is presented here (INPDR).

Method: The INPDR is a patient-led, independent registry that collects prospective and retrospective clinical data from Niemann-Pick disease patients via the internet. To analyze the demographic, genetic, and clinical aspects of the disease, baseline data from NPC patients registered in the INPDR from September 2014 to December 2019 was retrieved.

Results: This study comprised a total of 203 NPC patients from six European countries. At the time of diagnosis, the average age (SD) was 11.2 years (14.2). There were 168 individuals with known neurological manifestations among the enrolled patients: 43 (24.2%) had early-infantile onset, 47 (26.4%) had lateinfantile onset, 41 (23.0%) had juvenile onset, and 37 (20.8%) had adult onset. The newborn rapidly lethal systemic type was seen in 10 (5.6%) of the patients. The c. 3182T > C variant responsible for the p.lle1061Thr protein change was reported in 35.1% (N = 34) of the 97 patients with identified NPC1 variants. Patients with early-infantile and late-infantile neurological onset had the highest rates of hepatomegaly and neonatal jaundice. Splenomegaly was the most often reported symptom, with 80% of adult-onset patients reporting it. Cognitive impairment (78.5%), dysarthria (75.9%), ataxia (75.9%), vertical supranuclear gaze palsy (70.9%), and dysphagia (69.6%) were the most commonly reported neurological manifestations. The overall disability score for each neurological form was calculated using a 6-domain composite disability scale. Except for 'swallowing' and 'seizure,' the majority of individuals with neurological onset showed moderate to severe deficits in all domains. With increasing age of start of neurological symptoms, the age at diagnosis and death rose. Patients used miglustat in 62.4% of cases, while antiepileptics (32.9%), antidepressants (11.8%), and antacids were the most common symptomatic treatments (9.4%).

Conclusion: Across the cohort, the proportion of subjects at each age of neurological onset was relatively equal. Across all age groups, neurological symptoms such as ataxia, dysphagia, and dysarthria were common.

Keywords: Niemann-Pick Disease Type C, registry, neurological symptoms