The Natural History of Alpha-Mannosidosis (HUE-MAN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00498420
Recruitment Status : Completed
First Posted : July 10, 2007
Last Update Posted : September 2, 2016
European Commission
Information provided by (Responsible Party):
Chiesi Farmaceutici S.p.A. ( Zymenex A/S )

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?

Condition or disease
Alpha Mannosidosis

Detailed Description:


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.


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-mannosidosis include a broad range of symptoms, from an early lethal form to less symptomatic, chronic forms often initially diagnosed in childhood. Alpha-mannosidosis is frequently associated with corneal opacities, aseptic destructive arthritis, metabolic myopathy and immune deficiency. In the past alpha-mannosidosis was classified into two forms. A more severe infantile (type 1) phenotype that include rapid, progressive mental retardation; hepatosplenomegaly; severe dysostosis multiplex; and often death between 3 and 12 years of age. The juvenile-adult phenotype (type 2) is characterized by a milder and more slowly progressive course with survival into adulthood. The distinctions are not absolute, and symptoms and lethality may vary. In affected children that are born healthy, there is a window of opportunity for a therapy initiated at an early age to contribute to normal development and the prevention of other disease related complications.

Study objectives:

To assess the short-term, natural history of subjects diagnosed with Alpha-Mannosidosis To establish the range and diversity of clinical symptomatology To evaluate short term (24 months) changes in disease parameters

Study Type : Observational
Actual Enrollment : 45 participants
Time Perspective: Prospective
Official Title: A Multicenter, Multinational Study That Will Evaluate Clinical and Surrogate Parameters Known to be Affected in Alpha-Mannosidosis Patients
Study Start Date : May 2007
Actual Primary Completion Date : September 2009
Actual Study Completion Date : November 2009

Resource links provided by the National Library of Medicine

Biospecimen Retention:   Samples With DNA

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
To be eligible to proceed, each subject must meet all inclusion and exclusion criteria during the screening periode.

Inclusion Criteria:

  1. The patient (or patient's legal guardian) must provide written informed consent prior to performing any survey-related procedures.
  2. The patient must have a documented diagnosis of Alpha Mannosidosis, confirmed at screening by measurable clinical signs and symptoms of Alpha Mannosidosis
  3. Documented deficiency of serum or leukocyte acid alpha-mannosidase enzyme activity level

Exclusion Criteria:

  1. History of bone marrow transplantation.
  2. Use of an investigational drug within 30 days prior to study enrollment.
  3. Known medical condition, serious intercurrent illness, or other extenuating circumstance that may significantly decrease study compliance.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00498420

Czech Republic
Department of Pediatrics, Charles University
Prague, Czech Republic, 12000 Prague
University of Mainz
Mainz, Germany, 55101
Department of Medicine, University of Tromsoe
Tromsoe, Norway, N-9038
United Kingdom
Willink Biochemical Genetics Unit,. Royal Manchester Children's Hospital
Manchester, United Kingdom, M27 4HA
Sponsors and Collaborators
Zymenex A/S
European Commission
Principal Investigator: Michael Beck, MD Children's Hospital, University of Mainz
Principal Investigator: Ed Wraith, MD Willink Biochemical Genetics Unit, Royal Manchester Childern's Hospital
Principal Investigator: Jiri Zeman, MD Department of Pediatrics, Charles University
Principal Investigator: Dag Malm, MD Department of Medicine, University of Tromsoe

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Zymenex A/S Identifier: NCT00498420     History of Changes
Other Study ID Numbers: rhLAMAN-01
First Posted: July 10, 2007    Key Record Dates
Last Update Posted: September 2, 2016
Last Verified: September 2016

Keywords provided by Chiesi Farmaceutici S.p.A. ( Zymenex A/S ):
Rare disorder

Additional relevant MeSH terms:
Mannosidase Deficiency Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases