Achieving Congruence among Reference Laboratories for Absolute Abundance Measurement of Analytes for Rare Diseases: Psychosine for Diagnosis and Prognosis of Krabbe Disease.

Hamid Khaledi,Michael H. Gelb,Zackary Herbst,Coleman T. Turgeon,Sara Smith,Patrick D. DeArmond,Nancy B. Shoemaker,Dietrich Matern,Chad Biski,Joseph Orsini

doi:10.3390/ijns6020029

Abstract

Measurement of the absolute concentration of the biomarker psychosine in dried blood spots (DBS) is useful for diagnosis and prognosis of Krabbe disease and to support newborn screening of this leukodystrophy. As for assays for more common diseases, it is important to achieve congruence when multiple clinical laboratories provide testing. Four clinical laboratories, one research laboratory, and a commercial vendor collaborated with the goal to achieve congruence in quantitative psychosine measurement in DBS. A set of DBS calibrators was prepared by a single vendor and used in each reference laboratory to make a standard curve of measured psychosine in DBS versus the stated calibrator psychosine level. Congruence between the participating five laboratories was achieved using the psychosine DBS calibrators. This allowed application of disease-specific reference ranges obtained by the reference laboratory with the most extensive data by the other reference laboratories. Congruence between multiple reference laboratories in the measurement of the absolute concentration of biomarkers in DBS (and by extension other samples) is possible by the use of a common set of DBS calibrators.

Highlights

The glycosylsphingolipid psychosine has emerged as a biomarker for diagnosis and prognosis of Krabbe disease, a rare lysosomal storage disorder caused by deficiency of galactocerebrosidase (GALC) [1,2,3]
Psychosine measurement cannot yet replace GALC activity as a primary newborn screening test because it requires a mass spectrometer with a limit of detection lower than those typically used in newborn screening laboratories
Given the reference ranges for psychosine that have been established using dried blood spots (DBS) from confirmed patients with Krabbe disease with early and late onset symptoms [8], it is critical for reference laboratories to achieve precise measurement of absolute levels of psychosine in DBS

Summary

Introduction

The glycosylsphingolipid psychosine has emerged as a biomarker for diagnosis and prognosis of Krabbe disease, a rare lysosomal storage disorder caused by deficiency of galactocerebrosidase (GALC) [1,2,3]. Krabbe disease typically have psychosine values in be on low GALC activity alone is not sufficient for newborn screening. A few newborn screening laboratories include because it requires a mass spectrometer with a limit of detection lower than those typically used in psychosine analysis as a second-tier method [6], but most programs refer patients to diagnostic centers newborn screening laboratories.

Results

Conclusion