Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Analysis of Lyso-Globotriaosylsphingosine in Dried Blood Spots

  • Johnson, Britt (Division of Clinical and Translational Genetics, Department of Human Genetics, University of Miami, Miller School of Medicine) ;
  • Mascher, Hermann (Pharm-analyt Laboratories Inc.) ;
  • Mascher, Daniel (Pharm-analyt Laboratories Inc.) ;
  • Legnini, Elisa (University Children's Hospital) ;
  • Hung, Christina Y. (Division of Clinical and Translational Genetics, Department of Human Genetics, University of Miami, Miller School of Medicine) ;
  • Dajnoki, Angela (Division of Clinical and Translational Genetics, Department of Human Genetics, University of Miami, Miller School of Medicine) ;
  • Chien, Yin-Hsiu (National Taiwan University Hospital) ;
  • Marodi, Laszlo (Lysosomal Storage Disease Unit, Department of Infectious and Pediatric Immunology, Medical and Health Science Center, University of Debrecen) ;
  • Hwu, Wuh-Liang (National Taiwan University Hospital) ;
  • Bodamer, Olaf A. (Division of Clinical and Translational Genetics, Department of Human Genetics, University of Miami, Miller School of Medicine)
  • Published : 2013.07.01
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Abstract

Recently, lyso-globotriaosylsphingosine (lyso-Gb3) was found to be elevated in plasma of treatment naive male patients and some female patients with Fabry Disease (FD). This study tested whether lyso-Gb3 could be analyzed in dried blood spots (DBS) from filter cards and whether concentrations are elevated in newborn infants with FD. Lyso-Gb3 concentrations were analyzed in DBS following extraction using a novel HPLC-mass spectrometry (MS)/MS method. Lyso-Gb3 levels in DBS were above the lower limit of quantitation (0.28 ng/mL) in 5/17 newborn FD infants (16 males; range: 1.02-8.81 ng/mL), but in none of the newborn controls, in all 13 patients (4 males) with classic FD (range: 2.06-54.1 ng/mL), in 125/159 Taiwanese individuals with symptomatic or asymptomatic FD who carry the late onset ${\alpha}$-galactosidase A (GLA) mutation c.936+919G>A (IVS4+919G>A) ($3.75{\pm}0.69ng/mL$; range: 0.418-3.97 ng/mL) and in 20/29 healthy controls ($0.77{\pm}0.24ng/mL$; range: 0.507-1.4 ng/mL). The HPLC-MS/MS method for analysis of lyso-Gb3 is robust and yields reproducible results in DBS in patients with FD. However, concentrations of lyso-Gb3 were below the limit of quantitation in most newborn infants with FD rendering this approach not suitable for newborn screening. In addition, most females with the late onset mutation have undetectable lyso-Gb3 concentrations.

Keywords

References

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