J 2017

Lymphocyte Galactocerebrosidase Activity by LC-MS/MS for Post-Newborn Screening Evaluation of Krabbe Disease

LIAO, Hsuan-Chieh, Zdeněk SPÁČIL, Farideh GHOMASHCHI, Maria L. ESCOLAR, Joanne KURTZBERG et. al.

Basic information

Original name

Lymphocyte Galactocerebrosidase Activity by LC-MS/MS for Post-Newborn Screening Evaluation of Krabbe Disease

Authors

LIAO, Hsuan-Chieh (158 Taiwan), Zdeněk SPÁČIL (203 Czech Republic, guarantor, belonging to the institution), Farideh GHOMASHCHI (840 United States of America), Maria L. ESCOLAR (840 United States of America), Joanne KURTZBERG (840 United States of America), Joseph J. ORSINI (840 United States of America), Frantisek TURECEK (203 Czech Republic), C. Ronald SCOTT (840 United States of America) and Michael H. GELB (840 United States of America)

Edition

Clinical Chemistry, Washington, USA, AMER ASSOC CLINICAL CHEMISTRY, 2017, 0009-9147

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

20602 Medical laboratory technology ;

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 8.636

RIV identification code

RIV/00216224:14310/17:00097720

Organization unit

Faculty of Science

DOI

UT WoS

000406417600010

Keywords in English

UMBILICAL-CORD BLOOD; NEW-YORK-STATE; TRANSPLANTATION; SPOTS

Tags

Tags

International impact, Reviewed
Změněno: 6/4/2018 15:30, Ing. Nicole Zrilić

Abstract

V originále

BACKGROUND: Deficiency of the lysosomal enzyme galactosylcerebrosidase (GALC) causes Krabbe disease. Newborn screening for Krabbe disease is ongoing, but improved methods for follow-up analysis of screen-positive babies are needed to better advise families and to optimize treatment. We report a new assay for the enzymatic activity of GALC in lymphocytes. METHODS: T lymphocytes were isolated from venous blood by magnetic bead technology. The assay used a close structural analog of the natural substrate and LC-MS/MS to quantify the amount of product with the aid of a chemically identical internal standard. RESULTS: The analytical range of the assay (ratio of assay response for the QC high standard to that from all non-enzymatic-dependent processes) was 20-fold greater than that for the conventional radiometric GALC assay. The LC-MS/MS could distinguish cells that were null in GALC from those that contained traces of active enzyme (down to 0.3% of normal). There was a good correlation between the level of residual GALC activity in lymphocytes and the severity of Krabbe disease. CONCLUSIONS: The new assay can measure small amounts of residual GALC activity in leukocytes with high accuracy compared to previous assays and can contribute, along with genotyping, biomarker analysis, and neurological imaging, a better plan for post-newborn screening follow-up for Krabbe disease.