Alpha-mannosidosis
Lysosomal deposition diseases are a group of inherited disorders characterized by the abnormal accumulation of substances in cellular lysosomes due to altered enzymes that degrade them. Alpha-mannosidosis is part of this group of pathologies and is caused by a deficiency of the enzyme alpha-mannosidase, which is encoded by the MAN2B1 gene.
Alpha-mannosidosis causes immunodeficiency, intellectual deficit and skeletal disorders, among other clinical manifestations.
Its prevalence is not well known, but it is estimated to affect one individual in every million live births.
Symptoms
Affected children appear normal at birth, but their health progressively worsens. In some cases clubfoot is observed and they develop hydrocephalus in the first year of life. The main manifestations are: immune deficiency (leading to recurrent infections, especially in the first ten years of life), skeletal abnormalities (defective ossification, mild to moderate scoliosis and sternal deformities), hearing impairment (hearing loss), progressive impairment of mental functions and speech.
Facial alterations include large head size with prominent forehead and rounded eyebrows, flat nasal bridge, thickened tongue or macroglossia, widely spaced teeth and prognathism. Mild strabismus may often be present.
At the motor level, patients with alpha-mannosidosis often show muscle weakness, joint abnormalities and ataxia.
Prevention
Treatments focus on preventing complications and improving patients' quality of life. For example, antibiotics are used for bacterial infections, hearing aids for hearing loss, physiotherapy treatments and assistance from speech therapists and educators to facilitate learning and the proper development of social skills.
Velmanase alfa (Lamzede®) is a drug that has been approved by the EMA (European Medicines Agency) for the specific treatment of patients with alpha-mannosidosis with mild to moderate non-neurological symptoms.
Genes analyzed
