Disease progression of alpha-mannosidosis and impact on patients and carers - A UK natural history survey

Abstract

Introduction: Alpha-mannosidosis is an ultra-rare lysosomal storage disorder resulting from the deficient activity of lysosomal alpha-mannosidase. Alpha-mannosidosis presents as a highly heterogenous condition with large variations in symptom severity and disease progression rates. Quantitative and qualitative data for alpha-mannosidosis patients and their caregivers provide important insights into their daily experiences.

Methods: A survey of nine alpha-mannosidosis patients was carried out in the UK between August 2017 and January 2018. Patient demographics, health-related quality of life (HRQoL), and qualitative data from patients and carers relating to clinical characteristics and impact of the disease and treatment were analysed.

Results: At the time of survey completion, patient age ranged from 7 to 37 years. Five patients were described as 'walking unassisted', one as 'walking with assistance', one as 'wheelchair-dependent', and two as 'severely immobile'. In addition to best supportive care, three patients had received haematopoietic stem cell transplantation (HSCT) and one had received velmanase alfa enzyme replacement therapy (ERT). Patient HRQoL results for the EQ-5D-5 L questionnaire and the Health Utilities Index-3 showed that patients with more severe ambulatory health states reported lower utility values than patients who were more mobile. Patients who received HSCT or ERT experienced improved HRQoL. Carer HRQoL results for the Hospital Anxiety and Depression Scale and Caregiver Strain Index demonstrated that carers experience high levels of stress and anxiety from their caregiving responsibilities.

Conclusions: This survey confirmed the heterogeneity of alpha-mannosidosis and the large impact of the disease and treatment on patients, carers, and families. Early diagnosis and access to treatment offers the best chance of slowing the disease progression and may provide some relief to patients and carers.

Keywords: Alpha-mannosidosis; Enzyme replacement therapy; Haematopoietic stem cell transplantation; Lysosomal storage disorder; Quality of life; Velmanase alfa.

Fig. 1

HRQoL of nine patients as reported by proxy measured using the EQ-5D-5 L questionnaire according to walking ability (top) and prior treatment (bottom). A score of 1 indicates ‘perfect health’, a score of 0 indicates ‘death’. Negative values indicate ‘feeling worse than death’. Utility values for two patients were mapped from EQ-5D-Y to EQ-5D-5 L using the nonparametric crosswalk method [15]. Abbreviations: BSC, best supportive care; EQ-5D-5 L, EuroQol 5 Dimensions 5 Levels; ERT, enzyme replacement therapy; HRQoL, health-related quality of life; HSCT, haematopoietic stem cell transplantation; SI, severe immobility; WC, wheelchair-dependent; WU, walking unassisted; WWA, walking with assistance.

Fig. 2

HRQoL by domain of seven patients as reported by proxy measured using the EQ-5D-5 L questionnaire. Each line represents the carer-reported domain score by proxy for an individual patient (N = 7). Please note that identical scores were reported for patients 4 and 5 so these appear to be one line. Responses for the EQ-5D-Y questionnaire were completed for two patients; these are not represented here as each dimension on the EQ-5D-Y has three levels compared with five levels on the EQ-5D-5 L. Higher scores indicate a higher level of perceived problems for that domain of the EQ-5D-5 L questionnaire. Abbreviations: EQ-5D-5 L, EuroQol 5 Dimensions 5 Levels; EQ-5D-Y, EuroQol-5 Dimension-Youth; HRQoL, health-related quality of life.

Fig. 3

HRQoL of six patients as reported by proxy measured using the HUI-3 questionnaire by walking ability (top) and prior treatment (bottom). HUI-3 utility scores could be calculated for six patients; no data were available for the other three patients. Utility scores are calculated by applying a formula that attaches weights to each of the levels in each dimension. A utility score of 1 indicates ‘perfect health’, a value of 0 indicates ‘death’. Negative values indicate ‘feeling worse than death’. Abbreviations: BSC, best supportive care; ERT, enzyme replacement therapy; HUI-3, Health Utility Index–3; HRQoL, health-related quality of life; HSCT, haematopoietic stem cell transplantation; SI, severe immobility; WC, wheelchair-dependent; WU, walking unassisted; WWA, walking with assistance.

Fig. 4

QoL of carers measured by walking ability of the patient using the HADS questionnaire (top), CSI questionnaire (middle) and caregiver time per day (bottom) For HADS, carer scores for anxiety and depression subscales go up to 21 each. 0–7: no case; 8–10: borderline abnormal case; 11–21: abnormal case. For CSI, carer scores go up to 12, with a score of 7 or higher indicating the carer is under a high level of stress related to care provision. Blue horizontal dotted lines indicate the level at which there is a borderline abnormal case for HADS for each subscale or a high level of stress related to care provision for CSI. Abbreviations: CSI, Caregiver Strain Index; HADS, Hospital Anxiety and Depression Scale; HRQoL, health-related quality of life; SI, severe immobility; WC, wheelchair-dependent; WU, walking unassisted; WWA, walking with assistance. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)