Lysomal Storage Disorder

The Koala

Alpha-Mannosidosis

Alpha-mannosidosis, a glycoproteinosis, is due to a genetic defect of the lysosomal enzyme alpha-mannosidase that is responsible for the hydrolysis of glycoprotein carbohydrate moieties. The decreased activity of this enzyme leads to accumulation of oligosaccharides in several cells and organs. Alpha-mannosidosis is a slowly progressive disorder that shows a broad phenotypic variability. Clinical features include hearing impairment, skeletal abnormalities, impairment of mental function, sometimes periods of psychosis. In addition, muscular weakness and ataxia are observed. In the first decade of life recurrent infections occur due to an immune defect.

Alpha-Mannosidosis | SphinCS - Clinical Science for LSD

Etiology: Deficiency of alpha-mannosidase
Gene: MAN2B1 Gene
Mode of inheritance: Autosomal recessive
Phenotypes:

  • Infantile Form
  • Milder Form 

Leading symptoms:

Infantile form
(Age of onset: infancy)

  • Severe CNS manifestations
  • Severe immune deficiency
  • Hepatosplenomegy

Milder form
(Age of onset: childhood, adolescence)

  • Facial dysmorphia
  • Dysostosis multiplex
  • Hearing impairment
  • Immune deficiency
  • Psychomotor development delay
  • Cognitive impairment
  • Ataxia
  • Psychatric symptoms
  • Hepatosplenomegaly

Diagnostics:

  • Measurement of the activity of alpha-mannosidase in serum
  • Molecular genetic analysis of MAN2B1-Gene

Therapy:
Velmanase alfa (Lamzede®)

Current Studies

The "U.S. National Library of Medicine" provides a complete list of all international studies at www.clinicaltrials.gov. The comparable EU website is less comprehensive: www.clinicaltrialsregister.eu.

Self-help groups

At the moment we are not aware of any self-help groups.

Literature

Borgwardt L, Stensland HM, Olsen KJ, Wibrand F, Klenow HB, Beck M, Amraoui Y, Arash L, Fogh J, Nilssen Ø, Dali CI, Lund AM. 

Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation
Orphanet J Rare Dis. 2015 Jun 6;10:70.

Borgwardt L, Lund AM, Amraoui Y, Andersen O, De Meirleir L, Dolhem P, Campos MG, Guffon N, Heron B, Laroche C, Marquardt T, Mengel E, Muschol N, Tylki-Szymanska A, Van den Hout JMH, Van Der Ploeg A, Welling L, Wijburg F, Cole D, Fogh J, Geraci S, Ardigo D, Cattaneo F.

Long-term enzyme replacement therapy with velmanase alfa slows disease progression in adult patients suffering from alpha-mannosidosis
Molecular Genetics and metabolism 120: S30-S30.

Lund AM, Borgwardt L, Cattaneo F, Ardigò D, Geraci S, Gil-Campos M, De Meirleir L, Laroche C, Dolhem P, Cole D, Tylki-Szymanska A, Lopez-Rodriguez M, Guillén-Navarro E, Dali CI, Héron B, Fogh J, Muschol N, Phillips D, Van den Hout JMH, Jones SA, Amraoui Y, Harmatz P, Guffon N.

Comprehensive long-term efficacy and safety of recombinant human alpha-mannosidase treatment in patients with alpha-mannosidosis
J Inherit Metab Dis. 2018 Nov;41(6):1225-1233.

Borgwardt L, Guffon N, Amraoui Y, Dali CI, De Meirleir L, Gil-Campos M, Heron B, Geraci S, Ardigò D, Cattaneo F, Fogh J, Van den Hout JMH, Beck M, Jones SA, Tylki-Szymanska A, Haugsted U, Lund AM.

Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial
J Inherit Metab Dis. 2018 Nov;41(6):1215-1223.

Matlach J, Zindel T, Amraoui Y, Arash-Kaps L, Hennermann JB, Pitz S.

Retinal and optic nerve degeneration in α-mannosidosis
Orphanet J Rare Dis. 2018 Jun 1;13(1):88.

Dawn Phillips, Julia B. Hennermann, Anna Tylki-Szymanska, Line Borgwardt, Mercedes Gil-Campos, Nathalie Guffon, Yasmina Amraoui, Silvia Geraci, Diego Ardigò, Federica Cattaneo, Allan M. Lund.

Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosis
Mol Genet Metab Rep. 2020 Jun; 23: 100586.

Niemann, S., M. Beck, G. Seidel, J. Spranger, and P. Vieregge

Neurology of Adult Alpha-Mannosidosis
J Neurol Neurosurg Psychiatry 61, no. 1 (Jul 1996): 116-7.
Link to the publication

Borgwardt, L., C. I. Dali, J. Fogh, J. E. Mansson, K. J. Olsen, H. C. Beck, K. G. Nielsen, L. H. Nielsen, S. O. Olsen, H. M. Riise Stensland, O. Nilssen, F. Wibrand, A. M. Thuesen, T. Pearl, U. Haugsted, P. Saftig, J. Blanz, S. A. Jones, A. Tylki-Szymanska, N. Guffon-Fouiloux, M. Beck, and A. M. Lund

Enzyme Replacement Therapy for Alpha-Mannosidosis: 12 Months Follow-up of a Single Centre, Randomised, Multiple Dose Study
J Inherit Metab Dis 36, no. 6 (Nov 2013): 1015-24
Link to the publication

Beck, M., K. J. Olsen, J. E. Wraith, J. Zeman, J. C. Michalski, P. Saftig, J. Fogh, and D. Malm

Natural History of Alpha Mannosidosis a Longitudinal Study
Orphanet J Rare Dis 8, no. 1 (Jun 20 2013): 88.
Link to the publication

At present we have no literature available.

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