Analysis of lyso-globotriaosylsphingosine in dried blood spots

Britt Johnson, Hermann Mascher, Daniel Mascher, Elisa Legnini, Christina Y. Hung, Angela Dajnoki, Yin Hsiu Chien, László Maródi, Wuh Liang Hwu, Olaf A. Bodamer

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 a-galactosidase A (GLA) mutation c.936+919G<A (IVS4+919G<A) (3.75 ±0.69 ng/mL; range: 0.418-3.97 ng/mL) and in 20/29 healthy controls (0.77±0.24 ng/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.

Original languageEnglish
Pages (from-to)274-278
Number of pages5
JournalAnnals of Laboratory Medicine
Volume33
Issue number4
DOIs
StatePublished - Jul 24 2013

Fingerprint

Fabry Disease
Blood
Newborn Infant
Mass spectrometry
Tandem Mass Spectrometry
High Pressure Liquid Chromatography
Galactosidases
Asymptomatic Diseases
Mutation
globotriaosyl lysosphingolipid
Screening
Plasmas

Keywords

  • Dried blood spot
  • Fabry disease
  • Filter card
  • Tandem mass spectrometry

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Johnson, B., Mascher, H., Mascher, D., Legnini, E., Hung, C. Y., Dajnoki, A., ... Bodamer, O. A. (2013). Analysis of lyso-globotriaosylsphingosine in dried blood spots. Annals of Laboratory Medicine, 33(4), 274-278. https://doi.org/10.3343/alm.2013.33.4.274

Analysis of lyso-globotriaosylsphingosine in dried blood spots. / Johnson, Britt; Mascher, Hermann; Mascher, Daniel; Legnini, Elisa; Hung, Christina Y.; Dajnoki, Angela; Chien, Yin Hsiu; Maródi, László; Hwu, Wuh Liang; Bodamer, Olaf A.

In: Annals of Laboratory Medicine, Vol. 33, No. 4, 24.07.2013, p. 274-278.

Research output: Contribution to journalArticle

Johnson, B, Mascher, H, Mascher, D, Legnini, E, Hung, CY, Dajnoki, A, Chien, YH, Maródi, L, Hwu, WL & Bodamer, OA 2013, 'Analysis of lyso-globotriaosylsphingosine in dried blood spots', Annals of Laboratory Medicine, vol. 33, no. 4, pp. 274-278. https://doi.org/10.3343/alm.2013.33.4.274
Johnson B, Mascher H, Mascher D, Legnini E, Hung CY, Dajnoki A et al. Analysis of lyso-globotriaosylsphingosine in dried blood spots. Annals of Laboratory Medicine. 2013 Jul 24;33(4):274-278. https://doi.org/10.3343/alm.2013.33.4.274
Johnson, Britt ; Mascher, Hermann ; Mascher, Daniel ; Legnini, Elisa ; Hung, Christina Y. ; Dajnoki, Angela ; Chien, Yin Hsiu ; Maródi, László ; Hwu, Wuh Liang ; Bodamer, Olaf A. / Analysis of lyso-globotriaosylsphingosine in dried blood spots. In: Annals of Laboratory Medicine. 2013 ; Vol. 33, No. 4. pp. 274-278.
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