Penzien J M, Kappler J, Herschkowitz N, Schuknecht B, Leinekugel P, Propping P, Tønnesen T, Lou H, Moser H, Zierz S
Department of Pediatrics, University of Berne, Switzerland.
Am J Hum Genet. 1993 Mar;52(3):557-64.
Several allelic mutations at the arylsulfatase A (ASA) locus cause substantial deficiencies of this lysosomal enzyme. Depending on the genetically determined degree of the deficiency, the clinical outcome may be very different--either metachromatic leukodystrophy (MLD), a lethal lysosomal storage disorder affecting the nervous system, or, more frequently, the so-called pseudodeficiency (PD), which has no apparent clinical consequence. Because of compound heterozygosity for MLD and PD, 1/1,000 individuals in the population have low residual enzyme activities, which are intermediate between those of MLD patients and those of PD homozygous normal individuals. In order to assess whether PD/MLD compound heterozygotes bear a health risk, we examined clinically and biochemically 16 individuals with this genotype. Of these subjects, two had neurological symptoms and two showed lesions, without clinical symptoms, in magnetic resonance imaging of the brain. None of these symptoms was progressive, nor did they resemble those of MLD. Nerve conduction velocities were normal in these probands, and they secreted only low amounts of sulfatide in the urine. We conclude that the observed neurological symptoms are unrelated to the ASA genotype and that PD/MLD compound heterozygotes are not at an increased risk for developing progressive nervous system diseases.
芳基硫酸酯酶A（ASA）基因座上的几个等位基因突变会导致这种溶酶体酶的严重缺乏。根据基因决定的缺乏程度，临床结果可能大不相同——要么是异染性脑白质营养不良（MLD），一种影响神经系统的致命性溶酶体贮积症，要么更常见的是所谓的假缺陷（PD），它没有明显的临床后果。由于MLD和PD的复合杂合性，人群中每1000人中有1人具有低残留酶活性，其活性介于MLD患者和PD纯合正常个体之间。为了评估PD/MLD复合杂合子是否存在健康风险，我们对16名具有这种基因型的个体进行了临床和生化检查。在这些受试者中，两人有神经症状，两人在脑部磁共振成像中显示有病变但无临床症状。这些症状均无进展，也不像MLD的症状。这些先证者的神经传导速度正常，且他们尿液中仅分泌少量硫脂。我们得出结论，观察到的神经症状与ASA基因型无关，且PD/MLD复合杂合子发生进行性神经系统疾病的风险并未增加。
