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 physicians
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.
Find out how you can participate: 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 GmbH
Am Strande 7
18055 Rostock
Germany
Email: Sabine.Roesner(at)centogene(dot)com
Susanne Zielke, Clinical Research Associate
CENTOGENE GmbH
Am Strande 7
18055 Rostock
Germany
Email: Susanne.Zielke(at)centogene(dot)com
Dr. Snezana Skobalj, Clinical Research Associate
CENTOGENE GmbH
Am Strande 7
18055 Rostock
Germany
Email: Snezana.Skobalj(at)centogene(dot)com