Measurement of sulfatides in the amniotic fluid supernatant: A useful tool in the prenatal diagnosis of metachromatic leukodystrophy

JIMD Reports

Zackary M. Herbst¹  Jose A. A. Magalhães²  Carolina Moura Fischinger de Souza³  Thiago Oliveira³  Franciele B. Trapp³  Sandra Leistner‐Segal³  Maira Graeff Burin³  Ana Carolina Brusius‐Facchin³  Rejane Gus³  Matheus V. M. B. Wilke³  Maria Teresa Sanseverino³  Kristiane Michelin‐Tirelli³  Alice B. O. Netto⁴  Francyne Kubaski⁴  Roberto Giugliani⁴ 

[1]Department of Chemistry University of Washington Seattle Washington USA

[2]Fetal Medicine Unit HCPA, UFRGS Porto Alegre Brazil

[3]Medical Genetics Service HCPA Porto Alegre Brazil

[4]PPGBM UFRGS Porto Alegre Brazil

关键词: arylsulfatase A;    metachromatic leukodystrophy;    prenatal analysis;    sulfatides;    tandem mass spectrometry;   

DOI  :  10.1002/jmd2.12270

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown