Plasma globotriaosylsphingosine (lysoGb3) could be a biomarker for Fabry disease with a Chinese hotspot late-onset mutation (IVS4+919G>A).
BACKGROUND
Previous studies revealed a high incidence of late-onset Fabry disease mutation, IVS4+919G>A, in Taiwan. However, the natural course is largely unclear and suitable biomarkers for monitoring disease progress are unavailable.


RESULTS
Patients carrying IVS4+919G>A or classical Fabry mutations were enrolled in this study. The subjects ranged from newborn to eighty year old adults. Plasma globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3) were measured by LC-MS/MS in subjects to evaluate the sensitivity of these two biomarkers. All adult males and symptomatic females could be distinguished from healthy controls by an elevated plasma lysoGb3 level. The lysoGb3 level was also related to the left ventricular mass considering gender and age (p<0.01). Moreover, approximately 70% of male and 45% of female newborns already had an elevated plasma lysoGb3 level which increased gradually as the subjects got older (p<0.01).


CONCLUSIONS
Plasma lysoGb3 is a more sensitive and reliable biomarker than plasma Gb3. LysoGb3 also correlated with age and left ventricular mass index in Fabry patients with IVS4+919G>A mutation. Because lots of infants with the IVS4+919G>A mutation already had elevated lysoGb3 levels at birth, that indicates that the development of hypertrophic cardiomyopathy may require a long and insidious course after lysoGb3 accumulation.
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Chinese Foundation of Health, Section of Newborn Screening Center, Taipei, Taiwan; Taiwan Clinical Trial Consortium in Fabry Disease, Taiwan.
Hsuan-Chieh
HC
Liao
Yu-Hsiu
YH
Huang
Yann-Jang
YJ
Chen
Shu-Min
SM
Kao
Hsiang-Yu
HY
Lin
Chun-Kai
CK
Huang
Hao-Chuan
HC
Liu
Ting-Rong
TR
Hsu
Shuan-Pei
SP
Lin
Chia-Feng
CF
Yang
Cathy S J
CS
Fann
Pao-Chin
PC
Chiu
Kai-Sheng
KS
Hsieh
Yun-Ching
YC
Fu
Yu-Yuan
YY
Ke
Ching-Yuang
CY
Lin
Fuu-Jen
FJ
Tsai
Chung-Hsing
CH
Wang
Mei-Chyn
MC
Chao
Wen-Chung
WC
Yu
Chuan-Chi
CC
Chiang
Dau-Ming
DM
Niu
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D000795:Fabry Disease / Q000097:blood* / Q000201:enzymology / Q000235:genetics*; D005260:Female; D006017:Glycolipids / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013107:Sphingolipids / Q000097:blood*; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult; D000519:alpha-Galactosidase / Q000097:blood / Q000235:genetics
D015415:Biomarkers; D006017:Glycolipids; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid; D000519:alpha-Galactosidase
ERT; Fabry disease; Gb3; Hypertrophic cardiomyopathy; IVS4+919G>A; LC-MS/MS; LVMI; LysoGb3; Newborn screening; enzyme replacement therapy; globotriaosylceramide; globotriaosylsphingosine; high performance liquid chromatography mass spectrometry; left ventricular mass index