Francis G S, Bonni A, Shen N, Hechtman P, Yamut B, Carpenter S, Karpati G, Chang P L
Department of Neurology, McGill University, Montreal, Quebec, Canada.
Ann Neurol. 1993 Aug;34(2):212-8. doi: 10.1002/ana.410340218.
Metachromatic leukodystrophy is due to deficient activity of arylsulfatase A, an enzyme important in myelin catabolism. The deficiency can be caused by different point mutations in the gene coding for arylsulfatase A (nonfunctional alleles). In addition, certain mutations result in low levels of enzyme activity detectable with artificial substrates in vitro but no clinical dysfunction (pseudodeficiency alleles). The described family has various combinations of normal, nonfunctional, and pseudodeficiency alleles that presented diagnostic and counseling dilemmas which were resolved at the genomic level. We find no evidence that compound heterozygote individuals have subclinical involvement of the nervous system. We report the clinical, pathological, electrophysiological, imaging, biochemical, and genetic data of this family and discuss the difficulties in analyzing such pedigrees.
异染性脑白质营养不良是由于芳基硫酸酯酶A活性不足所致，该酶在髓鞘分解代谢中起重要作用。这种缺陷可能由编码芳基硫酸酯酶A的基因中的不同点突变（无功能等位基因）引起。此外，某些突变导致在体外用人造底物可检测到的酶活性水平较低，但无临床功能障碍（假缺陷等位基因）。所描述的家族具有正常、无功能和假缺陷等位基因的各种组合，这带来了诊断和咨询方面的难题，而这些难题在基因组水平上得到了解决。我们没有发现复合杂合子个体存在神经系统亚临床受累的证据。我们报告了这个家族的临床、病理、电生理、影像学、生化和遗传学数据，并讨论了分析此类家系的困难。
