Elevation of urinary globotriaosylceramide (GL3) in infants with Fabry disease.
BACKGROUND
Fabry disease is caused by a deficiency of α-galactosidase A (α-Gal A), which results in the accumulation of globotriaosylceramide (GL3) and related glycosphingolipids in different organs. Urinary GL3 levels increase in symptomatic Fabry disease patients, but it is not clear whether urinary GL3 excretion also increases in young or pre-symptomatic patients.


METHODS
Eighty-nine newborns with leukocyte α-Gal A activities of less than 30% of the normal mean were discovered by newborn screening. Urine samples were collected on filter paper, and GL3 levels were measured using liquid chromatography-tandem mass spectrometry.


RESULTS
Five newborns with classic Fabry disease mutations all had elevated urinary GL3 levels (mean=5.2 mg/mmol creatinine (creat.), range=0.80-14.39, normal <0.6). Among the 84 newborns with later-onset mutations, 45 (54%) had a mild elevation of urinary GL3 levels (mean=1.1 mg/mmol creat., range=0.60-3.07, normal <0.6). The urinary GL3 levels decreased in all newborns over the course of a three-year follow-up period. However, four children with classic mutations and seven with IVS4+919G>A mutations still had elevated GL3 levels at the end of the study.


CONCLUSIONS
Elevated urinary GL3 levels can be present at birth in Fabry disease patients, suggesting an early involvement of the kidneys in this disease. The increased urinary GL3 excretion in those with later-onset mutations supports a pathogenic role for these mutations.
Chien
Yin-Hsiu
YH
Department of Medical Genetics and Pediatrics, National Taiwan University Hospital and National Taiwan University School of Medicine, Taipei, Taiwan.
Olivova
Petra
P
Zhang
Xiaokui Kate
XK
Chiang
Shu-Chuan
SC
Lee
Ni-Chung
NC
Keutzer
Joan
J
Hwu
Wuh-Liang
WL
D000328:Adult; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D000795:Fabry Disease / Q000175:diagnosis / Q000652:urine*; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D009154:Mutation; D053719:Tandem Mass Spectrometry; D014281:Trihexosylceramides / Q000652:urine*; D000519:alpha-Galactosidase / Q000097:blood / Q000235:genetics
D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase