Elevation of urinary globotriaosylceramide (GL3) in infants with Fabry disease |
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| Authors: | Yin-Hsiu Chien Petra Olivova Xiaokui Kate Zhang Shu-Chuan Chiang Ni-Chung Lee Joan Keutzer Wuh-Liang Hwu |
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| Institution: | 1. Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan;2. Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan;3. Pathology Division, Gifu University Hospital, Gifu, Japan;1. New York State Dept. of Health, Wadsworth Center, Albany, NY 12201-0509, United States;2. Genzyme Corporation, 1 Mountain Rd., Framingham, MA 01701-09322, United States;3. Thomas Jefferson University, Department of Neurology, Philadelphia, PA 19107, United States;1. Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, USA;2. Agilent Technologies, Inc., Wakefield, MA, USA;3. Laboratory of Genetic Metabolic Disease, Academic Medical Center, University of Amsterdam, The Netherlands;4. Medical Genetics Service, HCPA and Department of Genetics, UFRGS, Porto Alegre, Brazil;5. Department of Pediatrics, Faculty of Medicine University of the Ryukyus, Okinawa, Japan;6. Department of Pediatrics, Shimane University, Izumo, Japan;7. Medical Education Development Center, Gifu University, Gifu, Japan;8. Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan |
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| Abstract: | BackgroundFabry 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 methodsEighty-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.ResultsFive 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.ConclusionElevated 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. |
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