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Alpha Mannosidosis: Information for Families & Professionals

Normal mannosidase

Until recently, the biochemical structure of normal mannosidase enzyme was unknown. In 1994, Tollersrud et al, extracted the enzyme from ox kidney and characterized the complete amino acid sequence and structure of human and the bovine and mannosidase molecule. Further work is published by Moremen et al. The human alpha-mannosidase is a big macromolecule of about 1000 amino acids, where 5 polypeptide chains are linked with disulphide bridges and supplied with sugar chains.

Abnormal mannosidase

Normal production of mannosidase would include the reading and translation of the DNA sequence and later modeling of the protein in the cell. Mannosidosis is due to a mutation which results in enhanced lysosomal degradation of the enzyme, changes in the active site or at the site of a cofactor. This results in the inability to attain an active conformation needed for enzymatic activity which is reduced or absent. Residual enzyme activity means the rest activity of the enzyme that is measured by analysis. In diseased cells of some patients, there is often a residual mannosidase activity of 1-10 % of normal.

 What can the residual activity of the enzyme tell us? In the literature, authors report confusing observation on the enzyme activity. The methods used in measuring enzyme activity may be different, the tissue where it is measured vary, there might be age differences, and the residual activity measured may not be lysosomal, but cytoplasmic or from the so-called Golgi apparatus. So therefore, it does not say much. One might think, that low activity means a worse, and high residual activity a better prognosis. This might be so, but we do not know if this is true. The correlation of genotype to phenotype is difficult. In the end hard data such as genotype or mannosidase activity must be correlated to phenotypic symptoms that are hard to quantify, such as immunodeficiency, morphological characteristics or IQ . From inbreed studies of Healy et al on Angus and Galloway cattle it is obvious that the mutations have various degree of severity. Berg et al have later depicted the mutation in Angus-cattle, and further found that this mutation is different from the Galloway. This further substantiates that there is an association between genotype and phenotype. In diseased cats, the same correlation between enzyme activity and survival is known.

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Page title: Clinical Information on Alpha Mannosidosis
URL: http://www.mannosidosis.org/alphaman/amanclinic.htm
Editor: Dag Malm; Webmaster: Paul Murphy
July 11, 2000