Bennet J K, Dembure P P, Elsas L J
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Am J Med Genet. 1995 Jan 2;55(1):21-6. doi: 10.1002/ajmg.1320550108.
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.
我们报告了两名患有不同表现形式的甘露糖苷贮积症的无关患者。一名患者在幼儿期就受到影响，具有I型甘露糖苷贮积症的严重表型特征。另一名患者直到成年后期出现进行性神经功能恶化后才被诊断为II型甘露糖苷贮积症。两者均通过对寡糖进行非侵入性尿液筛查检测出来。从两名患者血细胞转化而来的成淋巴细胞的溶酶体α-甘露糖苷酶活性明显降低。动力学分析表明，I型患者的α-甘露糖苷酶亲和力降低了400倍，而II型患者的则降低了40倍。所有4名父母的成淋巴细胞的α-甘露糖苷酶活性均降低，但这些I型和II型 obligate杂合子之间存在重叠活性。我们得出结论，筛查尿液寡糖将在广泛的表型范围内检测出甘露糖苷贮积症，受影响杂合子转化而来的成淋巴细胞的酶活性降低，并且临床表达的严重程度与酶损伤程度有关。
