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EUMAP Study

An international, multicenter, prospective analysis, exploring the prevalence of Alpha-Mannosidosis in a risk population.

Summary

Overview

This is an international, multicenter, epidemiological study, which is being conducted in 3 countries (Austria, Swizerland, and Germany), with a total of 1.000 participants to be enrolled. Targetted participants are aged between 2 months and 18 years old and have a family history of Alpha-Mannosidosis or are at risk for the disease, according to symptoms in the spheres of ENT, neuropediatrics, dentistry and/or orthopedics.

The objectives of this study are to investigate the prevalence of Alpha-Mannosidosis in participants at risk for Alpha-Mannosidosis and to establish biomarker/s in MAN2B1 positive cohort.


Study access on CentoPortal® for participating study doctors

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Study Rationale

Alpha-Mannosidosis is a rare lysosomal storage disorder (approx. 1: 500,000), characterized by a deficiency of the enzyme alpha-D-mannosidase. The disease is caused by mutations in the MAN2B1 gene (coding for this lysosomal enzyme), which leads to abnormal accumulation of oligosaccharides in the lysosomes. Cells start to malfunction and eventually die, which leads to further tissue and organ damage. There is generally little awareness of Alpha-Mannosidosis among physicians, therefore it is frequently under- or misdiagnosed.

Participant Benefits

The study’s goal is to explore and analyse the prevalence of Alpha-Mannosidosis disease in a cohort of 1,000 subjects with a suspicion of Alpha-Mannosidosis disease, based on the subject’s clinical symptoms.

Participants with positive MAN2B1 mutations receive a definitive diagnosis of Alpha-Mannosidosis.

Study Design

The subjects fulfilling the eligibility criteria will be enrolled in the Study and biochemically and genetically tested for Alpha-Mannosidosis. Therefore, all subjects will have a single research blood sample drawn, which will be equivalent to 30 drops (less than 1 mL). This will be applied to a CentoCard®, which will be sent to CENTOGENE and analyzed in CENTOGENE’s specialized laboratory.

In addition, past medical history and medication, family history, and physical examination findings will be recorded. All the above data will be collected on an electronic Case Report Form (eCRF).

When the CentoCard® arrives in CENTOGENE’s laboratory, the alpha-mannosidase activity will be biochemically analyzed first. In the case of a pathologic biochemical result, the MAN2B1 gene will be sequenced as a second step. This genetic test enables the detection of mutations and confirms a potential Alpha-Mannosidosis diagnosis.

All MAN2B1 mutation-positive blood samples will be further analyzed via mass spectrometry, in order to establish an AlphaMannosidosis specific biomarker/s. 

Information about the Study

Design: International, multicenter, epidemiological protocol

Study population: Participants with recurrent infections and/or skeletal abnormalities and/or hearing impairment-deafness and/or progressive neurological symptoms and/or impairment of mental functions and/or gingival hypertrophy and/or dysmorphic facial features and/or motoric disturbances of no obvious etiology.

Number of participants: 1,000

First participant in: March 2019

Last participant in: September 2020

Inclusion period (for all centers): 18 months

Objectives:

  • To investigate the prevalence of Alpha-Mannosidosis in participants

with recurrent infections

and/or

skeletal abnormalities

and/or

hearing impairment-deafness

and/or

progressive neurological symptoms

and/or

impairment of mental functions

and/or

gingival hypertrophy

and/or

dysmorphic facial features

and/or

motoric disturbances of no obvious etiology

  • To establish biomarker/s in MAN2B1 positive cohort.

ClinicalTrials.gov

Medical Facts

  • The prevalence of Alpha-Mannosidosis is not precisely known, but is estimated to occur in approximately 1 in 500,000 live births worldwide.
  • Affected children are born appearing ‘normal’, with their conditions progressively worsening.
  • The symptoms of Alpha-Mannosidosis can range from mild to severe:

    • in the most severe cases, an affected fetus may even die before birth.
    • symptoms may appear in infancy with rapid progression and severe neurological deterioration, and patients often do not survive past childhood.
    • symptoms in milder forms appear later and progress more slowly.

  • Systemic clinical manifestations of the disease include:

    • immune deficiency (recurrent infections)
    • facial abnormalities
    • skeletal abnormalities: dysostosis multiplex, scoliosis and deformation of sternum, genu valgus, destructive polyarthtropathy, coxarthrosis or gonarthrosis
    • hearing impairment or deafness
    • mental retardation
    • psychiatric symptoms (anxiety or depression)

  • Apart from supportive treatment, patients may benefit with enzyme replacement therapy  specific for this disease.

Inclusion Criteria
Informed consent is obtained from the participant’s parent/legal guardian
The participant is aged between 2 months and 18 years

The participant has a family history of Alpha-Mannosidosis or has one or more symptoms of no obvious etiology below

recurrent infections

and/or

skeletal abnormalities

and/or

hearing impairment-deafness

and/or

progressive neurological symptoms

and/or

impairment of mental functions

and/or

gingival hypertrophy

and/or

dysmorphic facial features

and/or

motoric disturbances


Exclusion Criteria
Informed consent is not provided by the participant’s parent/legal guardian
The participant is younger than 2 months or older than 18 years

The participant has no family history of Alpha-Mannosidosis and is not at risk for Alpha-Mannosidosis (represents none of the following symptoms of no obvious etiology):

recurrent infections

skeletal abnormalities

hearing impairment-deafness

progressive neurological symptoms

impairment of mental functions

gingival hypertrophy

dysmorphic facial features

motoric disturbances

Contact

Sabine Rösner, Project Lead
CENTOGENE AG
Am Strande 7
18055 Rostock
Germany
Email: Sabine.Roesner(at)centogene(dot)com

Susanne Zielke, Clinical Research Associate
CENTOGENE AG
Am Strande 7
18055 Rostock
Germany
Email: Susanne.Zielke(at)centogene(dot)com

Dr. Snezana Skobalj, Clinical Research Associate
CENTOGENE AG
Am Strande 7
18055 Rostock
Germany
Email: Snezana.Skobalj(at)centogene(dot)com


Study access on CentoPortal® for participating study doctors

CentoPortal®