European Alpha-Mannosidosis Participant

Deafness Clinical Trial

— EUMAP  

Official title:

European Alpha-Mannosidosis Participant: An International, Multicenter, Epidemiological Protocol

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03651245
• Other study ID #: EUMAP-2018
• Status: Terminated
• Start date: August 20, 2018
• Est. completion date: May 30, 2022

Study information

• Verified date: June 2022
• Source: CENTOGENE GmbH Rostock
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

International, multicenter, observational, longitudinal monitoring study to investigate the prevalence of Alpha-Mannosidosis in participants at risk for Alpha-Mannosidosis.

Description:

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

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 (hydrocephalus); hearing loss; and a clouding of the lens of the eye (cataract).

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. 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.

Modern methods, as DBS based mass-spectrometry give a great opportunity to

• Simplify the diagnostic process

• Simplify the logistics

• Increases stability and reproducibility

• Characterize specific metabolic alterations in the blood of affected patients that allow diagnosing the disease earlier, with a higher sensitivity and specificity.

A more specific diagnosis that permits earlier detection of the disease, as well as assessment of the disease activity and progression, would also permit improved chances for earlier treatment of those patients suffering from the disease.

It is the goal of this international, multicentre, epidemiological study to explore and analyse the prevalence of Alpha-Mannosidosis disease in a cohort of 1.000 patients with a suspicion of Alpha-Mannosidosis disease, based on the patient's clinical symptoms.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 667
• Est. completion date: May 30, 2022
• Est. primary completion date: May 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months to 18 Years

Eligibility

Inclusion Criteria:

• Informed consent is obtained from the participant's parent/legal guardian

• The participant is aged between 2 months and 18 years of age

• The participant has a family history of Alpha-Mannosidosis or is at risk for Alpha-Mannosidosis according to one or more of the following symptoms: recurrent infections, skeletal abnormalities, hearing impairment-deafness, progressive neurological symptoms, impairment of mental functions, gingival hypertrophy, dysmorphic facial features, motoric disturbances of no obvious etiology

Exclusion Criteria:

• Informed consent is not provided by the partici-pant'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): recurrent infections, skeletal abnormalities, hearing impairment-deafness, progressive neurological symptoms, impairment of mental functions, gingival hypertrophy, dysmorphic facial features, motoric disturbances of no obvious etiology

Related Conditions & MeSH terms

• alpha-Mannosidosis
• Deafness
• Facial Dysmorphism
• Gingival Hypertrophy
• Hypertrophy
• Immunodeficiency
• Intellectual Disability
• Mental Retardation
• Skeletal Abnormalities

Locations

Country	Name	City	State
Germany	Uniklinik RWTH Aachen Klinik für Kinder- und Jugendmedizin	Aachen
Germany	Charité - Universitätsmedizin Berlin, Leitung Sozialpädiatrisches Zentrum, Klinik für Pädiatrie m.S. Neurologie	Berlin
Germany	Carl-Thiem-Klinikum Cottbus GmbH, Klinik für Kinder und Jugendmedizin	Cottbus
Germany	Universitätsklinikum Essen, Klinik für Hals-Nasen und Ohrenheilkunde	Essen
Germany	Universitätsklinikum Gießen, Zentrum für Kinderheilkunde und Jugendmedizin, Abteilung für Kinderneurologie, Sozialpädiatrie und Epileptologie	Gießen
Germany	Universitätsklinikum Halle Universitätsklinik und Poliklinik für Pädiatrie I	Halle
Germany	UKE - Universitätsklinikum Hamburg-Eppendorf Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde	Hamburg
Germany	Evangelisches Krankenhaus Hamm, Klinik für Kinder-und Jugendmedizin	Hamm
Germany	Medizinische Hochschule Hannover, Deutsches HörZentrum Hannover	Hannover
Germany	Universitätsklinikum Jena, Klinik für Hals-, Nasen- und Ohrenheilkunde	Jena
Germany	Universitätsklinikum Jena, Klinik für Neuropädiatrie	Jena
Germany	UNIVERSITÄTSKLINIKUM LEIPZIG AöR, Klinik und Poliklinik für Hals-, Nasen-, Ohrenheilkunde	Leipzig
Germany	Sozialpädiatrisches Zentrum der HTZ Neuwied gGmbH	Neuwied
Germany	Evangelisches Krankenhaus Oberhausen, Sozialpädiatrisches Zentrum	Oberhausen
Germany	Elblandkliniken Stiftung & Co. KG - Elblandklinkum Riesa Sozialpädiatrisches Zentrum und Frühförderstelle	Riesa
Germany	Klinik für Kinder-und Jungendmedizin des Universitätsklinikums Ulm	Ulm
Germany	Zentrum für Kinder und Jugendliche Sozialpädiatrisches Zentrum (SPZ) im Marien-Hospital	Wesel
Switzerland	HNO-Universitätsklinik, Universitätsspital Basel	Basel
Switzerland	Inselspital Bern Universitätsklinik für Neurologie	Bern

Sponsors (1)

Lead Sponsor	Collaborator
CENTOGENE GmbH Rostock

Countries where clinical trial is conducted

Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epidemiological analysis of the prevalence of Alpha-Mannosidosis disease in a cohort of patients with suspicion for Alpha-Mannosidosis, based on their clinical symptoms.	Number of identified Alpha-Mannosidosis patients, showing a mutation/pathogenic variant in the MAN2B1-Gene, within a cohort of 1000 suspected cases using respective patient's dry-blood sample for confirmatory genetic testing (NGS-based sequencing of MAN2B1-gene)	3 years
Secondary	Establishment of biomarker/s in MAN2B1 positive cohort.	Alpha-Mannosidosis-positive samples will be validated for the identification of potential biomarkers (based on MS/MS-Tandem spectroscopy) and compared with the merged control samples in order establish a disease-specific biomarker.	3 years

External Links

•   CENTOGENE is a rare disease company focused on transforming clinical, genetic, and biochemical data into medical solutions for patients