Evaluation of enzyme activity predictions for variants of unknown significance in Arylsulfatase A.

Continued advances in variant effect prediction are necessary to demonstrate the ability of machine learning methods to accurately determine the clinical impact of variants of unknown significance (VUS). Towards this goal, the ARSA Critical Assessment of Genome Interpretation (CAGI) challenge was designed to characterize progress by utilizing 219 experimentally assayed missense VUS in the () gene to assess the performance of community-submitted predictions of variant functional effects. The challenge involved 15 teams, and evaluated additional predictions from established and recently released models.

Predicting disease severity in metachromatic leukodystrophy using protein activity and a patient phenotype matrix.

Background: Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by mutations in the arylsulfatase A gene (ARSA) and categorized into three subtypes according to age of onset. The functional effect of most ARSA mutants remains unknown; better understanding of the genotype-phenotype relationship is required to support newborn screening (NBS) and guide treatment.

Results: We collected a patient data set from the literature that relates disease severity to ARSA genotype in 489 individuals with MLD.

Toward newborn screening of metachromatic leukodystrophy: results from analysis of over 27,000 newborn dried blood spots.

Purpose: Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulfatase A (ARSA), which results in the accumulation of sulfatides. Newborn screening for MLD may be considered in the future as innovative treatments are advancing. We carried out a research study to assess the feasibility of screening MLD using dried blood spots (DBS) from de-identified newborns.

Leukocyte and Dried Blood Spot Arylsulfatase A Assay by Tandem Mass Spectrometry.

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.

Developing a Newborn Resuscitation Telemedicine Program: A Follow-Up Study Comparing Two Technologies.

Early work has demonstrated that newborn resuscitation telemedicine programs (NRTPs) are feasible and improve the quality of high-risk newborn resuscitations in community settings. Research evaluating the telemedicine technology requirements for NRTPs is limited. To compare the quality and reliability of two telemedicine technologies for providing NRTP consults.