Lysomal Storage Disorder

The Koala

Alpha-Mannosidosis

Alpha-mannosidosis, a glycoproteinosis, is due to a genetic defect of the lysosomal enzyme alpha-mannosidose 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-mannosidosi is a slowly progressive disorder that shows a broad phenotypic variability. Clinical features include hearing impairment, skeletal abnormalities, impairment of 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

Mildere form
(Age of onset: childhood, adolescence)

  • Faciale 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

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

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

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

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

Retinal and optic nerve degeneration in α-mannosidosis

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

At present we have no literature available.