Biomarker for Mannosidosis Disease (BioMannosidosis)

Brief Title

Biomarker for Mannosidosis Disease (BioMannosidosis)

Official Title

Biomarker for Mannosidosis Disease - An International, Multicenter, Epidemiological Protocol

Brief Summary

      Development of a new MS-based biomarker for the early and sensitive diagnosis of Mannosidosis
      disease from blood (plasma)

Detailed Description

      Alpha-Mannosidosis is a rare lysosomal storage disorder of the Glycoprotein family of
      diseases and is closely related to Mucopolysaccharidoses.

      Alpha-Mannosidosis was first described by Dr Oekerman, from Lund in Sweden in 1967. There is
      another variant known as Beta-Mannosidosis, which is extremely rare and has produced a wide
      range of clinical abnormalities in the few patients described with this disorder.

      A Alpha-Mannosidosis is a rare inherited disorder that causes problems in many organs and
      tissues of the body. Affected individuals may have intellectual disability, distinctive
      facial features, and skeletal abnormalities. Characteristic facial features can include a
      large head, prominent forehead, low hairline, rounded eyebrows, large ears, flattened bridge
      of the nose, protruding jaw, widely spaced teeth, overgrown gums, and large tongue. The
      skeletal abnormalities that can occur in this disorder include reduced bone density
      (osteopenia), thickening of the bones at the top of the skull (calvaria), deformations of the
      bones in the spine (vertebrae), bowed legs or knock knees, and deterioration of the bones and

      Affected individuals may also experience difficulty in coordinating movements (ataxia);
      muscle weakness (myopathy); delay in developing motor skills such as sitting and walking;
      speech impairments; increased risk of infections; enlargement of the liver and spleen
      (hepatosplenomegaly); a buildup of fluid in the brain (hydrocepha-lus); hearing loss; and a
      clouding of the lens of the eye (cataract). Some people with Alpha-Mannosidosis experience
      psychiatric symptoms such as depression, anxiety, or hallucinations; episodes of psychiatric
      disturbance may be triggered by stressors such as having undergone surgery, emotional upset,
      or changes in routine.

      The signs and symptoms of Alpha-Mannosidosis can range from mild to severe. The disorder may
      appear in infancy with rapid progression and severe neurological deterioration. Individuals
      with this early-onset form of Alpha-Mannosidosis often do not survive past childhood. In the
      most severe cases, an affected fetus may die before birth. Other individuals with
      Alpha-Mannosidosis experience milder signs and symptoms that appear later and progress more
      slowly. People with later-onset alpha-mannosidosis may survive into their fifties. The
      mildest cases may be detected only through laboratory testing and result in few if any

      Alpha-mannosidosis is estimated to occur in approximately 1 in 500,000 people worldwide.

      Mutations in the MAN2B1 gene cause Alpha-Mannosidosis. This gene provides instructions for
      making the enzyme alpha-mannosidase. This enzyme works in the lysosomes, which are
      compartments that digest and recycle materials in the cell. With-in lysosomes, the enzyme
      helps break down complexes of sugar molecules (oligo-saccharides) attached to certain
      proteins (glycoproteins). In particular, alpha-mannosidase helps break down oligosaccharides
      containing a sugar molecule called mannose.

      Mutations in the MAN2B1 gene interfere with the ability of the alpha-mannosidase enzyme to
      perform its role in breaking down mannose-containing oligosaccharides. These oligosaccharides
      accumulate in the lysosomes and cause cells to malfunction and eventually die. Tissues and
      organs are damaged by the abnormal accumulation of oligosaccharides and the resulting cell
      death, leading to the characteristic features of Alpha-Mannosidosis.

      New methods, like mass-spectrometry give a good chance to characterize specific metabolic
      alterations in the blood (plasma) of affected patients that allow diagnosing in the future
      the disease earlier, with a higher sensitivity and specificity.

      Therefore it is the goal of the study to identify and validate a new biochemical marker from
      the plasma of the affected patients helping to benefit other patients by an early diagnose
      and thereby with an earlier treatment.

Study Type


Primary Outcome

Development of a new MS-based biomarker for the early and sensitive diagno-sis of Mannosidosis disease from blood (plasma)

Secondary Outcome

 Testing for clinical robustness, specificity and long-term stability of the bi-omarker


Alpha-Mannosidase B Deficiency

Study Arms / Comparison Groups

Description:  Patients with Mannosidosis disease or high-grade suspicion for Mannosidosis disease


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

August 20, 2018

Completion Date

August 2021

Primary Completion Date

August 2021

Eligibility Criteria

        Inclusion Criteria:

          -  Informed consent will be obtained from the patient or the parents before any study
             related procedures.

          -  Patients of both genders older than 2 months

          -  The patient has a diagnosis of Alpha-Mannosidosis disease or a high grade suspicion
             for Alpha-Mannosidosis disease

          -  High grade suspicion present, if one or more inclusion criteria are valid:

               -  Positive family anamnesis for Alpha-Mannosidosis disease

               -  rounded eyebrows

               -  large head

               -  large ears

               -  flattened bridge of the nose

               -  deformations of the bones in the spine (vertebrae)

        Exclusion Criteria:

          -  No Informed consent from the patient or the parents before any study related

          -  Patients of both gender younger than 2 months

          -  No diagnosis of Alpha-Mannosidosis disease or no valid criteria for profound suspicion
             of Alpha-Mannosidosis disease




2 Months - N/A


Peter Bauer, Prof., , 

Location Countries


Location Countries


Administrative Informations



Organization ID

BMA 06-2018

Responsible Party


Study Sponsor


Study Sponsor

Peter Bauer, Prof., Study Chair, Centogene GmbH

Verification Date

May 2021