Quality of life in patients with Niemann-Pick disease type C and their carers

Abstract

Niemann–Pick disease type C (NPC) is a rare, progressive neurodegenerative condition thatcauses marked difficulties in mobility, cognition, communication and executive functioning.These symptoms, alongside the extensive demands placed on caregivers, create a clear needfor tools that capture both clinical severity and the wider impact on quality of life (QoL). Existingapproaches, including generic patient-reported outcome measures and clinician-rated severityscales, do not fully reflect the complexity of living with NPC. The overall aim of this thesis wastherefore to strengthen understanding of QoL in NPC and to validate disease-specificmeasures appropriate for research and clinical practice.

A pragmatic mixed-methods design was used. Qualitative interviews with adults with NPC andcaregivers explored everyday experiences of QoL, identifying themes relating to uncertainty,symptom burden, loss of independence and the central role of family support. Data on existing,non-validated NPC-specific QoL measures for adults and children were gathered through across-sectional survey, and their psychometric properties were examined. Insights from theinterviews informed the interpretation of the results, including the factor structure suggestedby principal components analysis. Tests of reliability and validity indicated good internalconsistency and expected correlations with generic QoL measuresA pragmatic mixed-methods design was used. Qualitative interviews with adults with NPC andcaregivers explored everyday experiences of QoL, identifying themes relating to uncertainty,symptom burden, loss of independence and the central role of family support. Data on existing,non-validated NPC-specific QoL measures for adults and children were gathered through across-sectional survey, and their psychometric properties were examined. Insights from theinterviews informed the interpretation of the results, including the factor structure suggestedby principal components analysis. Tests of reliability and validity indicated good internalconsistency and expected correlations with generic QoL measures.

The thesis also evaluated a lay-reported version of the NPC Clinical Severity Scale. Cognitive interviews highlighted difficulties in the interpretation of several items, informing refinements to wording and structure. The revised scale was subsequently assessed in a cross-sectional survey of people with NPC and caregivers, with results showing acceptable internal consistency, no substantial floor or ceiling effects and predicted positive associations with QoL scores.

Taken together, these findings offer new insight into QoL in NPC and provide validated tools that support clinical monitoring and the evaluation of emerging therapies. More broadly, this work demonstrates the importance of patient-centred, disease-specific approaches when capturing QoL in rare, heterogeneous populations.

Date of Award	Nov 2025
Original language	English
Awarding Institution	Aston University
Supervisor	Rebecca Knibb (Supervisor) & Gemma Mansell (Supervisor)