Abstract
Background
Alpha-mannosidosis (OMIM 248500) (AM) is a rare lysosomal storage disease caused by a deficiency of the alpha-mannosidase enzyme. The typical signs consist of hearing impairment, intellectual disabilities, coarse facial features and motor function disturbances. We report on the cognitive function and activities of daily living in patients with AM.
Methods
Thirty five AM patients, age 6-35 years, were included in the study. As a cognitive function test, we used the Leiter international performance scale–revised (Leiter-R), which consists of two batteries: the visual function and reasoning battery and the memory and attention battery, the latter including a memory screening. Additional two questionnaires, The Childhood Health Assessment Questionnaire (CHAQ) and EQ-5D-5 L, were filled out.
Results
We found IQ in the range of 30-81 in our cohort. The total equivalent age (mental age) was significantly reduced, between 3-9 years old for the visual function and reasoning battery, between 2.3-10.2 years for the memory screening. Data suggested a specific developmental profile for AM with a positive intellectual development until the chronological age 10-12 years, followed by a static or slightly increasing intellectual level. All patients were to varying degrees socially and practically dependent and unable to take care of themselves in daily life.
Conclusions
Intellectual disability is a consistent finding in patients with alpha-mannosidosis but with extensive variation. We assess that this group of patients has, despite their intellectual disabilities, a potential for continuous cognitive development, especially during childhood and early teenage years. This should be included and supported in the individual educational planning.
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Acknowledgments
We want to express a special thanks to the patients and families for their participation and dedicated efforts in the studies.
We thank our study-site personnel Marianne Luiten, Sannie Mahncke, Pernille Strøm, Camilla Sørensen, Lærke Freiberg, Nanna Kjær, Josefine Gutte Koch, Kamille Fogh; Pia Ringholm and Susanne Rodholm, Lene Skammelsen, Zymenex A/S (Chiesi group), Hillerød, Denmark.
We thank EU-framework 7 program for supporting the ALPHA-MAN project economically.
We thank the entire ALPHA-MAN consortium and Ans van der Ploeg and Hannerieke van den Hout, Center for lysosomal and metabolic disease, Eramus MC, Rotterdam, The Netherlands; Frits Wijburg, Department of Pediatric Metabolic Disorders, Academic Medical Center, Amsterdam, The Netherlands; Encarna Guillén-Navarro, Department of Pediatrics, Murcia, Spain; Christopher Lindberg, Neuromuscular Center, Department of Neurology, Sahlgrenska University Hospital, Sweden, for help with enrolment of patients.
Funding
The data described in this publication was generated by the ALPHA-MAN consortium and supported by the European Commission FP 7 Contract HEALTH.20102.4.4-1.
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Conflict of Interest
Thuesen, AM declares that she has no conflict of interest.
Olsen, KJ declares that he has no conflict of interest.
Dali, CI declares that she has no conflict of interest.
Lund, AM declares that he has no conflict of interest.
Borgwardt, L has received travel expenses for a scientific meeting by Zymenex A/S (Chiesi group). No other reimbursements/fees/funds/salaries have been accepted.
Fogh, J: The data in the paper are based on baseline data from clinical trials in which Zymenex A/S (Chiesi group) provides the investigational recombinant human enzyme Lamazym (rhLAMAN). The authors, except Fogh J who is employed at Zymenex A/S (Chiesi group), are not employed by Zymenex A/S (Chiesi group) and confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.
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Communicated by: Carla E. Hollak
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Borgwardt, L., Thuesen, A.M., Olsen, K.J. et al. Cognitive profile and activities of daily living: 35 patients with alpha-mannosidosis. J Inherit Metab Dis 38, 1119–1127 (2015). https://doi.org/10.1007/s10545-015-9862-4
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DOI: https://doi.org/10.1007/s10545-015-9862-4