Kappler J, Leinekugel P, Conzelmann E, Kleijer W J, Kohlschütter A, Tønnesen T, Rochel M, Freycon F, Propping P
Institut für Humangenetik der Universität, Bonn, Federal Republic of Germany.
Hum Genet. 1991 Mar;86(5):463-70. doi: 10.1007/BF00194634.
Arylsulfatase A (ASA) is a lysosomal enzyme that hydrolyzes sulfatide. Absence of ASA activity leads to metachromatic leukodystrophy (MLD). The clinical outcome resulting from ASA deficiency is highly variable with respect to age of onset and symptoms. So far the causes for the variability are poorly understood. We have studied the relationship between the ASA genotype and the clinical phenotype. Fibroblasts from a total of 34 subjects with low ASA activity were examined with immunoblotting, a sensitive ASA assay, and the sulfatide loading test in order to characterize low ASA activity further. By these methods, three different classes of ASA deficiency can be defined: homozygosity for the pseudodeficiency allele (ASAp), compound heterozygosity for the ASAp and MLD (ASA-) alleles, and ASA-/ASA- genotypes. These genotypes exhibit different levels of ASA residual activity. Only ASA-/ASA- genotypes are associated with MLD. For diagnostic purposes, however, the differentiation of the various ASA genotypes is essential.
芳基硫酸酯酶A（ASA）是一种可水解硫脂的溶酶体酶。ASA活性缺失会导致异染性脑白质营养不良（MLD）。ASA缺乏导致的临床结果在发病年龄和症状方面差异很大。到目前为止，这种变异性的原因还知之甚少。我们研究了ASA基因型与临床表型之间的关系。为了进一步表征低ASA活性，我们对总共34名ASA活性较低的受试者的成纤维细胞进行了免疫印迹、灵敏的ASA检测和硫脂负荷试验。通过这些方法，可以定义三种不同类型的ASA缺乏：假缺陷等位基因（ASAp）的纯合子、ASAp和MLD（ASA-）等位基因的复合杂合子以及ASA-/ASA-基因型。这些基因型表现出不同水平的ASA残余活性。只有ASA-/ASA-基因型与MLD相关。然而，出于诊断目的，区分各种ASA基因型至关重要。
