Clinical Trial: The Natural History of Alpha-Mannosidosis

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: A Multicenter, Multinational Study That Will Evaluate Clinical and Surrogate Parameters Known to be Affected in Alpha-Mannosidosis Patients

Brief Summary: The natural history study of the rare lysosomal disease alpha-mannosidosis will answer the question; why the rare disease develops as it does?

Detailed Summary:

Definition:

Human alpha-mannosidosis is a rare genetic disorder, caused by the lack of lysosomal alpha-mannosidase, resulting in mental retardation, skeletal changes, hearing loss and recurrent infections. The lack of alpha-mannosidase causes a disorder of glycoprotein catabolism associated with abnormal levels and excretion of small mannose-rich oligosaccharides.

Prevalence:

Alpha-mannosidosis belongs to a group of lysosomal storage disorders that includes more than 50 different diseases, with a cumulative frequency of about 1:10.000 world wide. The incidence of alpha-mannosidase disease has been estimated to be 1 in 500.000 (Australian and Norwegian study). The disease is not specific to any ethnic group.

Etiology and Pathogenesis:

Lysosomal alpha-mannosidase (LAMAN), in the following called mannosidase, is an enzyme that cleaves alpha-mannosidic linkages during the ordered degradation of oligosaccharides. Only after degradation, can the sugars leave the lysosomes, the cell and later the body. The deficiency in mannosidase activity causes a block in the degradation of glycoproteins resulting in lysosomal accumulation of mannose-rich oligosaccharide chains. Consequently, these sugars accumulate in the lysosomes as they are too large to leave. Finally, the lysosomes increase in size, producing vacuoles and impaired cellular function is induced by an unknown mechanism.

Clinical Findings:

Affected children are usually born apparently normal and their condition worsens progressively without any possible treatment available to prevent this evolution. The clinical findings in alpha-
Sponsor: Zymenex A/S

Current Primary Outcome:

Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Chiesi Farmaceutici S.p.A.

Dates:
Date Received: July 9, 2007
Date Started: May 2007
Date Completion:
Last Updated: September 1, 2016
Last Verified: September 2016