Alpha-mannosidosis

Read more about this disease, some with Classification – Types – Signs and symptoms – Genetics – Pathophysiology – Diagnosis – Screening – Prevention – Treatment and management – Cures and much more, some including pictures and video when available.

Alpha-mannosidosis is an autosomal recessive[1] lysosomal storage disorder [2] caused by deficient activity of the enzyme alpha-D-mannosidase.

A defective a-mannosidase enzyme, which normally helps to break down complex sugars derived from glycoproteins in the lysosome, causes sugar build up and impair cell function. Complete absence of functional enzyme leads to death during early childhood due to deterioration of the central nervous system. Enzyme with low residual activity leads to a milder type of the disease, with symptoms like reduced hearing, mental retardation, susceptibility to bacterial infections and skeletal deformities. The course of the disease is progressive.

Alpha-Mannosidosis is classified into types I through III based on severity and age of onset. In contrast to the usual classifications scheme of these disorders, type III is the most severe.

Symptoms range widely in their onset and severity. The onset of the most severe form, type III, begins within the first months of life and includes a quick progression of mental retardation, liver and spleen enlargement (splenomegaly), hearing loss, respiratory infections and skeletal abnormalities. Often the appearance of an affected individual includes the following coarse facial features: protruding forehead, leveled nasal bridge, small nose and wide mouth. Muscular weakness or spinal abnormalities can occur due to the build up of storage materials in the muscle. A milder form of Alpha-mannosidosis involves mild to moderate mental retardation which develops during childhood or adolescence.

A diagnosis is made by measuring the enzymatic activity of alpha-D-mannosidase in white blood cells. If there is a decreased level of the enzyme in comparison to standard levels, a diagnosis can be made. It is thought that this disorder might be under diagnosed for a few different reasons — the diagnosis is often made late in the disease’s progression, symptoms are often mild, or the biochemical diagnosis does not yield conclusive results.

The life expectancy in Alpha-mannosidosis is highly variable. Individuals with early onset severe disease often do not survive beyond childhood, whereas those with milder disorders may survive well into adult life.

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