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At a glance

It is a lysosomal glycoprotein storage disease characterized by 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 cerebral dysfunction, severe ataxia, deafness, scoliosis, rheumatoid arthritis, hypotonia, and muscle pain. Two types have been described: α and β mannosidosis. The α-Mannosidosis displays clinical heterogeneity, ranging from very serious to very mild forms. The β-Mannosidosis causes a severe disorder that affects the peripheral and central nervous systems.

Synonym

Lysosomal Mannosidosis Deficiency Syndrome.

History

It was 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 recurrent infections.

Classifications

There are two types of mannosidosis that consists of:

  • α-Mannosidosis: It is divided into three subtypes, ie, I to III. Type III is the most severe with an onset within the first few months of infancy. Clinical features include quick progression toward severe mental retardation, hepato- and splenomegaly, hearing loss, respiratory infections, and skeletal abnormalities. A milder form of α-mannosidosis involves mild-to-moderate intellectual disability that develops during childhood or adolescence. This disease belongs to a larger group of lysosomal storage disorder and is caused by a deficiency in the enzyme alpha-D-mannosidase. It is inherited as an autosomal recessive genetic mutation.

  • β-Mannosidosis (Lysosomalβ-Mannosidase Deficiency): It is a very rare form of mannosidosis involving a defect in the metabolism of oligosaccharide as a result of a decreased activity of the enzyme β-mannosidase. Clinically, individuals affected appear normal at birth. Within few months, severe neurodegeneration progressing to intellectual disability associated with hearing loss and angiokeratomas are seen. The exact incidence and international distribution remains unknown.

Incidence

The worldwide incidence of α-mannosidosis is established at 1:500,000 to 1:1,000,000 in the general population. It is found in all ethnic groups in Europe, America, Africa, and Asia. There are approximately 100 cases of α-mannosidosis and 15 cases of β-mannosidosis reported in the literature.

Genetic inheritance

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.

Pathophysiology

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.

Diagnosis

Usually made by measuring enzyme activity in white blood cells and eventually by measuring certain substances in urine. Increased ...

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