CLINICAL-ANALYSIS AND BIOCHEMICAL-ANALYSIS OF 2 FAMILIES WITH TYPE-I AND TYPE-II MANNOSIDOSIS

We report on two unrelated patients with different presentations of ma nnosidosis. One patient was affected in early childhood with a severe phenotype characteristic of type I mannosidosis. The other was diagnos ed with type II mannosidosis only after the onset of progressive neuro logic deterioration in late adulthood, Both were detected by non-invas ive urinary screening of oligosaccharides. Lymphoblasts transformed fr om both patients' blood cells had markedly reduced lysosomal alpha-man nosidase activity, Kinetic analyses showed that alpha-mannosidase from the type I patient had a 400-fold reduction in affinity while that fr om the type II patient was reduced 40-fold, Lymphoblasts from all 4 pa rents had reduced alpha-mannosidase activity, but there were overlappi ng activities among these type I and type II obligate heterozygotes. W e conclude that screening urinary oligosaccharides will detect mannosi dosis over a wide range of phenotypes, that lymphoblasts transformed f rom affected heterozygotes have decreased enzymatic activity, and that the severity of clinical expression is related to the degree of enzym e impairment. (C) 1995 Wiley-Liss, Inc.