Clinical trial NCT03651245: European Alpha-Mannosidosis Participant
Official title: European Alpha-Mannosidosis Participant: An International, Multicenter, Epidemiological Protocol
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Immunodeficiency
Skeletal Abnormalities
Deafness
Mental Retardation
Gingival Hypertrophy
Facial Dysmorphism
Keywords: Alpha-Mannosidosis disease
prevalence
Lead sponsor: CENTOGENE GmbH Rostock
Sponsor class: INDUSTRY
First posted: 2018-08-29
Enrollment: 667
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants at risk for Alpha-Mannosidosis

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Epidemiological analysis of the prevalence of Alpha-Mannosidosis disease in a cohort of patients with suspicion for Alpha-Mannosidosis, based on their clinical symptoms.
timeFrame: 3 years
Secondary outcomes:
measure: Establishment of biomarker/s in MAN2B1 positive cohort.
timeFrame: 3 years
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen Klinik für Kinder- und Jugendmedizin
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Leitung Sozialpädiatrisches Zentrum, Klinik für Pädiatrie m.S. Neurologie
city: Cottbus
country: Germany
facility: Carl-Thiem-Klinikum Cottbus GmbH, Klinik für Kinder und Jugendmedizin
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Hals-Nasen und Ohrenheilkunde
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen, Zentrum für Kinderheilkunde und Jugendmedizin, Abteilung für Kinderneurologie, Sozialpädiatrie und Epileptologie
city: Halle
country: Germany
facility: Universitätsklinikum Halle Universitätsklinik und Poliklinik für Pädiatrie I
city: Hamburg
country: Germany
facility: UKE - Universitätsklinikum Hamburg-Eppendorf Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde
city: Hamm
country: Germany
facility: Evangelisches Krankenhaus Hamm, Klinik für Kinder-und Jugendmedizin
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Deutsches HörZentrum Hannover
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Klinik für Hals-, Nasen- und Ohrenheilkunde
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Klinik für Neuropädiatrie
city: Leipzig
country: Germany
facility: UNIVERSITÄTSKLINIKUM LEIPZIG AöR, Klinik und Poliklinik für Hals-, Nasen-, Ohrenheilkunde
city: Neuwied
country: Germany
facility: Sozialpädiatrisches Zentrum der HTZ Neuwied gGmbH
city: Oberhausen
country: Germany
facility: Evangelisches Krankenhaus Oberhausen, Sozialpädiatrisches Zentrum
city: Riesa
country: Germany
facility: Elblandkliniken Stiftung & Co. KG - Elblandklinkum Riesa Sozialpädiatrisches Zentrum und Frühförderstelle
city: Ulm
country: Germany
facility: Klinik für Kinder-und Jungendmedizin des Universitätsklinikums Ulm
city: Wesel
country: Germany
facility: Zentrum für Kinder und Jugendliche Sozialpädiatrisches Zentrum (SPZ) im Marien-Hospital
city: Basel
country: Switzerland
facility: HNO-Universitätsklinik, Universitätsspital Basel
city: Bern
country: Switzerland
facility: Inselspital Bern Universitätsklinik für Neurologie
Study officials:
affiliation: CENTOGENE GmbH
name: Peter Bauer, Prof. Dr.
role: STUDY_CHAIR
References: