Leukocyte and Dried Blood Spot Arylsulfatase A Assay by Tandem Mass Spectrometry.
Xinying HongArun Babu KumarJessica DaikerFan YiMartin SadilekFabiola De MattiaFrancesca FumagalliValeria CalbiRoberta DamianoMaria Della BonaGiancarlo la MarcaAdeline L VanderverAmy T WaldmanLaura AdangOmar SherbiniSarah WoidillTeryn SuhrJoanne KurtzbergMaria L Beltran-QuinteroMaria EscolarAlessandro AiutiAlan FinglasAmber OlsenMichael H GelbPublished in: Analytical chemistry (2020)
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays were developed to measure arylsulfatase A (ARSA) activity in leukocytes and dried blood spots (DBS) using deuterated natural sulfatide substrate. These new assays were highly specific and sensitive. Patients with metachromatic leukodystrophy (MLD) and multiple sulfatase deficiency (MSD) displayed a clear deficit in the enzymatic activity and could be completely distinguished from normal controls. The leukocyte assay reported here will be important for diagnosing MLD and MSD patients and for monitoring the efficacy of therapeutic treatments. ARSA activity was measured in DBS for the first time without an antibody. This new ARSA DBS assay can serve as a second-tier test following the sulfatide measurement in DBS for newborn screening of MLD. This leads to an elimination of most of the false positives identified by the sulfatide assay.
Keyphrases
- high throughput
- liquid chromatography tandem mass spectrometry
- deep brain stimulation
- simultaneous determination
- tandem mass spectrometry
- solid phase extraction
- end stage renal disease
- high performance liquid chromatography
- liquid chromatography
- peripheral blood
- ejection fraction
- newly diagnosed
- chronic kidney disease
- high resolution
- ms ms
- peritoneal dialysis
- mass spectrometry
- nitric oxide