A lysosomal storage disorder characterized by ☞Hurler-like facial features, moderate-to-severe mental retardation, recurrent pulmonary infections, reduced hearing, immunodeficiency, skeletal abnormalities, and primary central nervous system disease. It is also frequently associated with corneal opacities, aseptic destructive arthritis, and metabolic myopathy. Communicating hydrocephalus can occur at any age. Cardiac and renal complications are rarely encountered. Alpha-mannosidosis is insidiously progressive. Individuals may live into the sixth decade.
Lysosomal Alpha-D-Mannosidase Deficiency; Alpha-Mannosidase B Deficiency; Mannosidosis.
The prevalence of Alpha-Mannosidosis is in the range of 1 to 3 in 1,000,000. The disease is not limited to any ethnic group as individuals from all parts of the world have been described.
Autosomal recessive. About 40 different mutations have been described that affect the gene for the lysosomal enzyme Alpha-Mannosidase, class 2B, member 1 (MAN2B1, MANB), which has been mapped to chromosome 19p13.13.
There are three different types of Alpha-Mannosidosis:
Type I (Mild Form): Mild form delineated by clinical recognition of the disease after 10 years of age, with a lack of skeletal abnormalities, myopathy, and slow progression.
Type II (Moderate Form): Moderate form with clinical recognition before the age of 10 years, with presence of skeletal abnormalities, myopathy, and slow progression with development of ataxia in the third decade of life. This is the most common type.
Type III (Severe Form): Severe form immediately recognized with obvious progression, leading to early death due to primary central nervous system involvement and/or severe infections (eg, pneumonia, gastroenteritis, urinary tract infections).
Alpha-Mannosidosis belongs to a group of inherited disorders known as lysosomal storage disorders. The enzyme defect within the lysosomes affects the normal turnover and breakdown of glycoproteins, which normally are processed by proteinases and glycosidases into fragments and then either transported to the cytosol for reuse or excreted. The lack or deficiency of Alpha-Mannosidase results in the progressive accumulation of undigested oligosaccharides in lysosomes throughout the body.
The diagnosis relies on demonstration of deficient acid alpha-mannosidase enzyme activity in peripheral blood leukocytes or other nucleated cells, such as fibroblasts, amniocytes, or the trophoblast. The diagnosis can be confirmed by measuring the presence of urinary oligosaccharides. Alpha-Mannosidase is needed in the catabolism of several oligosaccharides and glycoproteins. Prenatal testing for at risk families is possible.
Infiltration of tissues with oligosaccharides and glycoproteins results in tall stature, metabolic myopathy, muscular hypotonia, mental retardation, dilated cerebral ventricles and raised intracranial pressure, cerebellar atrophy, ataxia, macro-/hydrocephaly, thickened calvaria, coarse facial features (Hurler-like [but often less pronounced] with frontal bossing, midface hypoplasia, prognathism, macroglossia), low anterior hairline, thick eyebrows, sensorineural hearing loss, flat nose, large ears, cataract, widely spaced teeth with ...