Elevation of urinary globotriaosylceramide (GL3) in infants with Fabry disease

Abstract 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. Subjects and 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 A mutations still had elevated GL3 levels at the end of the study. Conclusion 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.