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

Population

Participants at risk for Alpha-Mannosidosis

Brief Title

European Alpha-Mannosidosis Participant

Official Title

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

Brief Summary

International, multicenter, observational, longitudinal monitoring study to investigate the <br /> 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.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.