european alpha-mannosidosis participant

Conditions: Immunodeficiency; Skeletal Abnormalities; Deafness; Mental Retardation; Gingival Hypertrophy; Facial Dysmorphism

Summary: international, multicenter, observational, longitudinal monitoring study to investigate the prevalence of alpha-mannosidosis in participants at risk for alpha-mannosidosis.

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

Keywords: alpha-mannosidosis disease prevalence