Elevation of urinary globotriaosylceramide (GL3) in infants with Fabry disease
Journal
Molecular Genetics and Metabolism
Journal Volume
102
Journal Issue
1
Pages
57-60
Date Issued
2011
Author(s)
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 <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. 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. ? 2010 Elsevier Inc.
SDGs
Other Subjects
alpha galactosidase; creatinine; globotriaosylceramide; article; enzyme activity; Fabry disease; female; gene mutation; human; liquid chromatography; major clinical study; male; newborn; newborn screening; priority journal; tandem mass spectrometry; urinary excretion; urine level; Adult; alpha-Galactosidase; Case-Control Studies; Chromatography, Liquid; Fabry Disease; Follow-Up Studies; Humans; Infant, Newborn; Leukocytes; Male; Mutation; Tandem Mass Spectrometry; Trihexosylceramides
Type
journal article