Mannosidosis

Lysosomal glycoprotein storage disease with mental retardation, hearing loss, and recurrent infections (upper or lower respiratory tract, and gastrointestinal tract). Other clinical features include coarse face, prominent forehead, prominent jaw, diffuse dysfunction of the brain, severe ataxia, deafness, scoliosis, rheumatoid arthritis, hypotonia, and muscle pain. Two types are described: α and β. α-Mannosidosis displays clinical heterogeneity, ranging from very serious to very mild forms. β-Mannosidosis causes a severe disorder that affects the peripheral and central nervous systems.

Lysosomal Mannosidosis Deficiency Syndrome.

First reported in 1967 by Oeckerman in Lund, Sweden, who described a boy affected with mental retardation, increased tissue total mannose concentration, and susceptibility to infection.

Rare; approximately 100 cases of α-mannosidosis and 10 to 15 cases of β-mannosidosis have been described. Found in all ethic groups in Europe, America, Africa, and Asia.

Autosomal recessive genetic disorder, 2.5:1 male preponderance. The α-mannosidase gene maps to chromosome 19p13.2-q12. The β-mannosidase gene is located at chromosome 4q22-25. Prenatal diagnosis is possible.

α-Mannosidosis is a disorder of glycoprotein catabolism associated with abnormal levels and excretion of mannose-rich oligosaccharides, caused by a deficiency of its catabolic enzyme α-mannosidase. β-Mannosidosis results from β-mannosidase deficiency with an increase in the corresponding oligosaccharide. Both enzymes are located in the lysosomes.

Usually made by measuring enzyme activity in white blood cells and eventually by measuring certain substances in urine. Increased urinary oligosaccharides as measured by thin-layer chromatography confirms the type. Measuring activity in lymphoblasts correlates with severity. Pathology shows multiple vacuoles in lymphocytes and hepatocytes. Clinical history and physical findings are considered important in the diagnosis.

Facies: The very typical facial characteristics of mannosidosis are a coarse face, a prominent forehead, a flattened nasal bridge, a small nose, and prominent jaw. Cerebral symptoms: The disease causes a diffuse dysfunction of the brain characterized by delayed early landmarks of neural development and severe ataxia. Hearing problems: Central and peripheral deafness. Immunodeficiency: Recurrent infections are a main feature of the disease. These infections are in the upper or lower respiratory tract, middle ear, or gastrointestinal tract. Skeletal: Scoliosis, rheumatoid arthritis, ataxia. Muscular: Muscular pain and weakness, which is caused by accumulation of storage material in the muscle and usually contributes to the immobilization of the patient.

α-Mannosidosis: Type I or severe infantile phenotype (onset between 3 and 12 months) includes rapid, progressive mental retardation, coarse facies resembling mucopolysaccharidosis, hepatosplenomegaly, dysostosis multiplex, recurrent bacterial infections with death between 3 and 12 years. Type II or juvenile-adult phenotype (onset between 1 and 4 years) is milder and slowly progressive with survival into adulthood. Other clinical features include spastic paraplegia (vertebral bodies abnormalities) and pancytopenia. In both types, deafness, cataracts, corneal opacifications, and vacuolated lymphocytes are present. Recurrent infections could be caused by a defect in leukocyte chemotaxis. Dysostosis multiplex causes skeletal dysplasia, ovoid configuration or flattening of the vertebral bodies, and kyphosis.