Clinical and biochemical analysis of two families with type I and type II mannosidosis.

Abstract

We report on two unrelated patients with different presentations of mannosidosis. One patient was affected in early childhood with a severe phenotype characteristic of type I mannosidosis. The other was diagnosed with type II mannosidosis only after the onset of progressive neurologic deterioration in late adulthood. Both were detected by non-invasive urinary screening of oligosaccharides. Lymphoblasts transformed from both patients' blood cells had markedly reduced lysosomal alpha-mannosidase activity. Kinetic analyses showed that alpha-mannosidase from the type I patient had a 400-fold reduction in affinity while that from the type II patient was reduced 40-fold. Lymphoblasts from all 4 parents had reduced alpha-mannosidase activity, but there were overlapping activities among these type I and type II obligate heterozygotes. We conclude that screening urinary oligosaccharides will detect mannosidosis over a wide range of phenotypes, that lymphoblasts transformed from affected heterozygotes have decreased enzymatic activity, and that the severity of clinical expression is related to the degree of enzyme impairment.

• Authors: J K Bennet, P P Dembure, L J Elsas
• Journal: American journal of medical genetics (Am J Med Genet) Vol. 55 Issue 1 Pg. 21-6 (Jan 02 1995) ISSN: 0148-7299 [Print] United States
• PMID: 7702090 (Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Oligosaccharides
• Mannosidases
• alpha-Mannosidase
• beta-N-Acetylhexosaminidases

Topics

• Adult
• Cells, Cultured
• Child
• Child, Preschool
• Clinical Enzyme Tests
• Female
• Genes, Recessive
• Humans
• Infant
• Kinetics
• Lymphocytes (enzymology)
• Male
• Mannosidases (deficiency)
• Oligosaccharides (urine)
• Substrate Specificity
• alpha-Mannosidase
• alpha-Mannosidosis (diagnosis, genetics)
• beta-N-Acetylhexosaminidases (blood)