Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 7;20(1):217.
doi: 10.1186/s13023-025-03694-4.

Evolution of mobility, pain/discomfort, self-care, and mental health in patients with alpha-mannosidosis: an international caregiver and patient survey

Karolina M Stepien  1 , Sophie Thomas  2 , Julia B Hennermann  3 , Christina Lampe  4 , Nicole M Muschol  5 , Maria Juliana Ballesta-Martínez  6 , Jordi Cruz  7 , Mónica López-Rodríguez  8 , Anneliese Barth  9 , Martin Magner  10 , Allan M Lund  11 , Vasilica Plaiasu  12 , Andrea Ballabeni  13 , Francesca Donà  13 , Heather M Morgan  14 , Nathalie Guffon  15
Affiliations

Evolution of mobility, pain/discomfort, self-care, and mental health in patients with alpha-mannosidosis: an international caregiver and patient survey

Karolina M Stepien et al. Orphanet J Rare Dis. .

Abstract

Background: Alpha-mannosidosis is a rare recessive lysosomal storage disorder with progressive multi-systemic impacts. In the absence of standardized monitoring protocols, there is insufficient understanding of disease progression over time. This study explored the evolution of the burden of illness and quality of life (QoL) experienced by patients with alpha-mannosidosis via an international patient and caregiver-based survey. The online survey was distributed to adult patients/caregivers of patients ≥ 10 years old. It included visual analogue scales (VAS; timepoints 5 years ago and now), multiple choice, and open text questions. We report a subset of functional and QoL data: walking ability, pain/discomfort, ability to self-care, and mental health.

Results: Analyses include 51 responses from 18 countries: 26 patients were on velmanase alfa enzyme replacement therapy (ERT), seven had been treated with hematopoietic stem cell transplantation (HSCT) and 18 were untreated patients (UP). Over 5 years, VAS scores showed the least decline in walking ability for HSCT patients (+ 0.1 ± 1.9) compared to patients receiving ERT (+ 0.7 ± 1.2) and UP (+ 1.8 ± 2.0). A trend towards improvement in pain was only observed for those on ERT (-0.2 ± 2.0), both for pediatric and adult patients. Ability to self-care improved for patients treated with HSCT (-1.0 ± 1.8) and slightly improved with ERT (-0.3 ± 1.5) but worsened for UP (+ 0.6 ± 0.9). Similarly, a trend towards improvement in mental health scores was observed for patients on ERT (-0.4 ± 2.2).

Conclusions: Alpha-mannosidosis is associated with a substantial and progressive burden in UP, including deterioration in walking ability, pain, self-care and mental health. The survey results suggest that treatment with ERT or HSCT may slow this natural progression of alpha-mannosidosis, with these patients following a different disease trajectory to those solely receiving supportive care. This study could inform the natural pathway of alpha-mannosidosis to recognize patients' needs, courses of care, and the design of interventional studies.

Keywords: Alpha-mannosidosis; Mental health; Pain; Self-care; Survey; Walking.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: RDRP conducted this market research in accordance with the British Healthcare Business Intelligence Association’s (BHBIA) Legal & Ethical Guidelines for Market Research. In line with these standards, this market research did not require review of a Research Ethics Committee because it falls outside the remit of the UK Research Governance Framework. The confidentiality of information gathered during the study is protected in accordance with applicable data protection legislation and BHBIA’s Legal & Ethical Guidelines. Informed consent was obtained online from all participants in their local language at the start of the online survey. Respondents to the survey had to confirm they were 18 years old or over. Those not providing consent were screened out and were not able to continue with the survey. Consent for publication: Consent was obtained from participants for the use of quotes and publication. Competing interests: KMS: PI for SPARKLE registry, consulting fees and/or honoraria/travel support from Chiesi, Sanofi Genzyme, BioMarin, and Takeda, Immedica. ST: The MPS Society has received money from Chiesi for participation and chairing of advisory boards, satellite symposiums (participation, time, travel & accommodation), Fabry matters conference, patient support services, mental health services, website re-development, consultation fees for review of lay materials. JBH: Received consulting fees and/or honoraria from Chiesi, Sanofi, Takeda, Amicus, and Immedica as well as travel support from Chiesi and Amicus. CL: Has received research grants, speakers’ honoraria and/or consultation fees from Chiesi, Amicus, Alexion, BioMarin, Sanofi, and Takeda. NMM: Has received research grants, speakers’ honoraria and/or consultation fees from Chiesi, Amicus, BioMarin, JCR, Lysogene, Sanofi, and Takeda. MJBM: PI for SPARKLE registry, no competing interests. JC: No competing interests. MLR: Has received research grants, speakers’ honoraria and/or consultation fees from Chiesi, Amicus, Sanofi, and Takeda. AB: Has received consulting fees and/or honoraria/travel support from BioMarin, Chiesi Farmaceutici S.p.A., Sanofi Genzyme, and Takeda. MM: PI for SPARKLE registry, consulting fees and/or honoraria/travel support from Chiesi, BioMarin, and Takeda. AML: Has received hospital grants as a PI for studies from Chiesi Farmaceutici S.p.A. as well as consulting fees and/or honoraria/travel support from Alexion, BioMarin, Chiesi Farmaceutici S.p.A., Sanofi Genzyme, and Shire. VP: PI for SPARKLE registry, speakers’ honoraria/travel support and/or consulting fees from BioMarin, Chiesi, Sanofi Genzyme, Shire/Takeda. AB: Former employee of Chiesi Farmaceutici S.p.A. during the time of this study. FD: Employee of Chiesi Farmaceutici S.p.A. HMM: Employee of Chiesi USA Inc. NG: Has received hospital grants as well as consulting fees and/or honoraria/travel support from BioMarin, Chiesi Farmaceutici S.p.A., JCR pharmaceuticals, Sanofi winthrop, Ultragenyx, and Takeda.

Figures

Fig. 1
Fig. 1
Flow diagram of respondents included in the analysis
Fig. 2
Fig. 2
Walking ability. Respondents were asked to rate the person with alpha-mannosidosis’ ability to walk 5 years ago and now on a VAS, where 0 was ‘no problem walking about’ and 10 was ‘unable to walk about’. (a) Mean (± SD) change in VAS scores 5 years ago to now, stratified by treatment (ERT, HSCT, UP), pediatric (< 16 years old) vs adults (≥ 16 years old), and length of time receiving ERT (< 5 years; ≥5 years); (b) Individual changes in VAS scores for ERT, HSCT, and UP. Green shows improvement, grey no change, and purple worsening/decline; (c) Help required to walk or move around 5 years ago and now for patients receiving ERT (n = 26), those who had received a HSCT (n = 7), and UP (n = 18). Respondents could select as many responses as it applied, hence percentages were calculated as number of patients who chose this option over the number of total patients who responded to this question. ERT = enzyme replacement therapy; HSCT = hematopoietic stem cell transplantation; SD = standard deviation; UP = untreated patients; VAS = visual analogue scale
Fig. 3
Fig. 3
Pain or discomfort. Respondents were asked to rate the person with alpha-mannosidosis’ pain or discomfort now and 5 years ago on a VAS, where 0 was ‘no pain or discomfort’ and 10 was ‘the worst possible pain or discomfort’. (a) Mean (± SD) change in VAS scores 5 years ago to now for pain or discomfort, stratified by treatment (ERT, HSCT, UP), pediatric (< 16 years old) vs adults (≥ 16 years old) and length of time receiving ERT (< 5 years; ≥5 years); (b) Individual changes in VAS scores for ERT, HSCT, and UP. Green shows improvement, grey no change, and purple worsening/decline; (c) Percentage of patients reporting pain or discomfort now in different parts of the body by treatment: ERT (n = 17), HSCT (n = 6), and UP (n = 10). Respondents could select as many responses as applied. Hence, percentages are calculated as number of patients who chose this option over the number of total patients who responded to this question. ERT = enzyme replacement therapy; HSCT = hematopoietic stem cell transplantation; SD = standard deviation; UP = untreated patients; VAS = visual analogue scale
Fig. 4
Fig. 4
Ability to self-care. Respondents were asked to rate the person with alpha-mannosidosis’ ability to perform self-care activities (e.g., washing, dressing, combing hair, brushing teeth, etc.) now and 5 years ago on a VAS scale, where 0 was being ‘able to do these activities completely independently’ and 10 was being ‘unable to do these activities for themselves, needing complete assistance’. (a) mean (± SD) change in VAS scores 5 years ago to now stratified by treatment (ERT, HSCT, UP), pediatric (< 16 years old) vs adults (≥ 16 years old) and length of time receiving ERT (< 5 years; ≥5 years). (b) Individual changes in VAS scores for ERT, HSCT, and UP. Green shows improvement, grey no change, and purple worsening/decline. ERT = enzyme replacement therapy; HSCT = hematopoietic stem cell transplantation; SD = standard deviation; UP = untreated patients; VAS = visual analogue scale
Fig. 5
Fig. 5
Mental health. Respondents were asked to rate the mental health of the person with alpha-mannosidosis on a VAS scale now and 5 years ago, where 0 was ‘excellent mental health’ and 10 was ‘poor mental health’. (a) Mean (± SD) change in VAS scores 5 years ago to now stratified by treatment group (ERT, HSCT, UP), pediatric (< 16 years old) vs adults (≥ 16 years old) and length of time receiving ERT (< 5 years; ≥5 years). (b) Individual changes in VAS scores reported by patients showing scores 5 years ago and now for ERT, HSCT, and UP. Green shows improvement, grey no change, and purple worsening/decline; (c) Percentage of mental health issues reported by patients by treatment over the past 12 months: ERT (n = 23), HSCT (n = 7), and UP (n = 16). Respondents could select as many responses as applied. Hence, percentages are calculated as number of patients who chose this option over the number of total patients who responded to this question. ERT = enzyme replacement therapy; HSCT = hematopoietic stem cell transplantation; SD = standard deviation; UP = untreated patients; VAS = visual analogue scale
See this image and copyright information in PMC

References

    1. OMIM®. Mannosidosis, Alpha B, Lysosomal, MANSA. Available online: https://www.omim.org/entry/248500. (Accessed: 6 February 2024).
    1. Malm D, Nilssen Ø. Alpha-mannosidosis. Orphanet J Rare Dis. 2008;3:21. - PMC - PubMed
    1. Malm D, Nilssen Ø. Alpha-mannosidosis. Orphanet encyclopedia. Available online: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en%26Expert=61. (Accessed: 2 January 2024).
    1. Ficicioglu C, Stepien KM. Alpha-Mannosidosis. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, et al. editors. GeneReviews(®). Seattle (WA): University of Washington, Seattle. Copyright © 1993–2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 2001. Oct 11 [updated 2024 Jun 13].
    1. Hennermann JB, Guffon N, Cattaneo F, Ceravolo F, Borgwardt L, Lund AM, et al. The SPARKLE registry: protocol for an international prospective cohort study in patients with alpha-mannosidosis. Orphanet J Rare Dis. 2020;15(1):271. - PMC - PubMed

Grants and funding