PDF(Pubmed)
Abstract：
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by deficiency of arylsulfatase A (ARSA), leading to an accumulation of sulfatides. Sulfatides have been quantified in urine, dried blood spots (DBS), and tissues of patients with MLD. Newborn screening (NBS) for MLD has already been proposed based on a two-tier approach with the quantification of sulfatides in DBS followed by the quantification of ARSA by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Prenatal screening for MLD is also crucial, and sulfatide quantification in amniotic fluid (AF) can aid diagnosis. The prenatal study was initiated due to a family history of MLD at 19 weeks of gestation. ARSA was quantified in cultured amniocytes. C16:0 sulfatide was quantified by LC-MS/MS in the supernatant of AF. Molecular analysis of the ARSA gene was performed in cultured amniocytes. ARSA was deficient in fetal cells, and C16:0 sulfatides were significantly elevated in comparison to age-matched controls (3-fold higher). Genetic studies identified the c.465+1G>A variant in homozygosis in the ARSA gene. Our study shows that sulfatides can be quantified in the supernatant of AF of MLD fetuses, and it could potentially aid in a faster and more accurate diagnosis of MLD patients.
摘要：
转移性脑白质营养不良(MLD)是一种由芳基硫酸酯酶A(ARSA)缺乏引起的常染色体隐性遗传性溶酶体疾病,导致硫苷脂的积累。尿中的硫化物已经定量,干血斑（DBS），和MLD患者的组织。已经提出了针对MLD的新生儿筛查（NBS）基于两层方法，该方法对DBS中的硫酸盐进行定量，然后通过液相色谱-串联质谱法（LC-MS/MS）对ARSA进行定量。产前筛查MLD也至关重要,羊水（AF）中的硫苷脂定量可以帮助诊断。由于妊娠19周时有MLD家族史，因此开始了产前研究。在培养的羊膜细胞中定量ARSA。通过LC-MS/MS在AF的上清液中定量C16:0硫苷脂。在培养的羊膜细胞中进行ARSA基因的分子分析。ARSA缺乏胎儿细胞,与年龄匹配的对照组相比，C16：0硫酸盐显着升高（高3倍）。遗传研究鉴定了ARSA基因中纯合性的c.465+1G>A变体。我们的研究表明，可以在MLD胎儿AF的上清液中定量硫酸盐，它可能有助于更快，更准确地诊断MLD患者。
