Alpha-Mannosidosis is an inherited lysosomal storage disease characterized by immune deficiency, facial and skeletal abnormalities, hearing impairment, and intellectual deficit.
It occurs in approximately 1 in 500,000 live births.
The disease is caused by a deficiency of lysosomal alpha-mannosidase. Alpha-Mannosidosis is hereditary, is transmitted in an autosomal recessive manner and is caused by mutations in the MAN2B1 gene, located on chromosome 19 (19 p13.2-q12).
The diagnosis is established by measuring the activity of acid alpha-mannosidase in leukocytes or other nucleated cells and can be confirmed by genetic testing. The increase in high mannose oligosaccharides in urine is indicative (nondiagnostic) disease.
The differential diagnosis includes other lysosomal storage diseases, such as various forms of mucopolysaccharidosis.
Genetic counseling should be proposed to explain the nature of the disease and locate individuals carrying the mutation.
Prenatal diagnosis is possible, based on both biochemical and genetic methods.
Affected infants appear normal at birth, but his health gets progressively worse. However, some children are born with clubfoot or develop hydrocephalus in the first year of life. The main manifestations are: immune deficiency (manifested by recurrent infections, particularly in the first ten years of life), skeletal anomalies (multiple disostosis, mild to moderate scoliosis and deformation of the sternum), hearing impairment (sensorineural hearing loss of moderate to severe), progressive disorder of mental functions and speech, and often, periods of psychosis.
Disorders of motor functions include: muscle weakness, joint abnormalities and ataxia.
The facial dysmorphism is characterized by large head with prominent forehead, rounded eyebrows, flat nasal bridge, macroglossia, widely spaced teeth, and prognathism. Often a slight strabismus. Is significant clinical variability that represents a continuous within gravity.
Management of the affected person should be proactive, to prevent complications and treat symptoms. Frequent infections should be treated. Often treatment of Otolaryngology of fluid buildup in the middle ear is necessary and, in some cases, is required the use of hearing aids.
Early support is required for the development of social skills, and physiotherapy is important to improve bodily functions.
Moreover, orthopedic surgery may be necessary.
Gene or region studied