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. 2017 Aug;62(8):763-768.
doi: 10.1038/jhg.2017.36. Epub 2017 Mar 30.

Successful newborn screening for Gaucher disease using fluorometric assay in China

Lulu Kang  1 , Xia Zhan  1 , Xuefan Gu  1 , Huiwen Zhang  1
Affiliations

Successful newborn screening for Gaucher disease using fluorometric assay in China

Lulu Kang et al. J Hum Genet. 2017 Aug.

Abstract

Gaucher disease (GD) is an inherited metabolic disorder that involves accumulation of glycolipid glucocerebroside in monocyte-macrophage cells, which can result in multiple organ damage. Enzyme replacement and substrate reduction therapies have improved the potential for early diagnosis and treatment. Determining the true incidence of this rare disease is critical for relevant policy establishment. Newborn screening allows for early diagnosis and an comparatively accurate incidence of GD. A fluorometric method to detect acid β-glucocerebrosidase (GBA) activity on a dried blood spot punch was developed. Validity and feasibility of the fluorometric method was demonstrated by examining 116 healthy controls, 19 confirmed GD patients and 19 obligate carriers. GBA activity was measured on dried blood spots of 80 855 newborns. Samples from positively screened newborns were reanalyzed by a leukocyte GBA activity test and GBA gene analysis. Plasma glucosylsphingosine level was determined as a biomarker of the pathophysiology of GD. GD patients were distinguished from healthy controls and obligate carriers using the fluorometric method. Mean GBA activity in newborn screening specimens was 145.69±44.76 μmol l-1 h-1 (n=80 844). Three children had low GBA activity, of which one child had low GBA activity on the second dried blood spot specimen. Leukocyte, genetic and biomarker analysis confirmed the diagnosis and indicated that this child was in the early stages of GD. In conclusion, the incidence of GD in Shanghai of China is approximately 1 in 80 855. Screening for GD by fluorometric analysis of GBA activity is an efficient and feasible technology in newborns.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Enzyme activities in dried blood spots among healthy controls, obligate carriers and confirmed patients. Boxes represent interquartile ranges. Top and bottom bars indicate limits of the ranges and central bars within the boxes represent median values. A full color version of this figure is available at the Journal of Human Genetics journal online.
Figure 2
Figure 2
Enzyme activities in newborns. Dotted line represents threshold for normal activity. Boxes represent interquartile ranges. Top and bottom bars indicate limits of the ranges and central bars represent median values. A full color version of this figure is available at the Journal of Human Genetics journal online.
Figure 3
Figure 3
Flowchart of Gaucher disease screening.
See this image and copyright information in PMC

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