Leistner S, Young E, Meaney C, Winchester B
Division of Biochemistry and Genetics, Institute of Child Health, London, UK.
J Inherit Metab Dis. 1995;18(6):710-6. doi: 10.1007/BF02436761.
A benign deficiency (pseudodeficiency) of the lysosomal enzyme arylsulphatase A (ASA) (EC 3.1.6.8) towards synthetic substrates complicates the diagnosis of metachromatic leukodystrophy (MLD). The pseudodeficiency is due to a single base substitution in the 3'-untranslated region of the ASA gene (1524+95 A-->G) and it has been reported that this mutation (PD2) always occurs on a chromosome carrying a second mutation in the ASA gene (PD1), which abolishes an N-glycosylation site (N350S). Analysis of the two PD mutations in the ASA gene separately was carried out in a large group of subjects with neurological symptoms and low ASA activity, including close relatives and MLD patients. The relationship between ASA enzyme activity and the different genotypes identified is presented. Evidence for the existence of an allele containing the PD2 mutation alone is presented. A strategy for cases with low ASA activity and neurological symptoms in families carrying a PD allele or both PD and MLD alleles is proposed.
溶酶体酶芳基硫酸酯酶A（ASA）（EC 3.1.6.8）对合成底物的良性缺陷（假缺陷）使异染性脑白质营养不良（MLD）的诊断变得复杂。这种假缺陷是由于ASA基因3'-非翻译区的单个碱基替换（1524 + 95 A→G）引起的，并且据报道这种突变（PD2）总是发生在携带ASA基因第二个突变（PD1）的染色体上，该突变消除了一个N-糖基化位点（N350S）。在一大组有神经症状且ASA活性低的受试者中，包括近亲及MLD患者，分别对ASA基因中的两种PD突变进行了分析。呈现了ASA酶活性与所鉴定的不同基因型之间的关系。提供了仅含有PD2突变的等位基因存在的证据。针对携带PD等位基因或同时携带PD和MLD等位基因的家族中ASA活性低且有神经症状的病例，提出了一种策略。
