title: Fabry disease in children and the effects of enzyme replacement treatment.
abstract: Fabry disease is a rare, X-linked inborn error of glycosphingolipid catabolism caused by a deficiency in the activity of the lysosomal enzyme, alpha-galactosidase A. In affected patients, the enzyme substrate, globotriaosylceramide (Gb3), accumulates in cells of various tissues and organs. Lysosomal accumulation of Gb3 begins in utero, and signs and symptoms of Fabry disease emerge in childhood and adolescence. The earliest presenting symptoms are typically neuropathic pain and gastrointestinal problems, which can have a substantial impact on health-related quality of life. Life-threatening major organ involvement is rare in young patients, but signs of kidney dysfunction (e.g., proteinuria), left ventricular hypertrophy, and stroke have been reported in children. There are two enzyme preparations for therapy: agalsidase alfa and beta. In two clinical trials of enzyme replacement therapy (ERT) with agalsidase alfa, including 37 children, boys demonstrated reductions in plasma Gb3 levels, and both boys and girls reported reductions in neuropathic pain and in the use of neuropathic pain medications. Heart rate variability, which is reduced in boys with Fabry disease, was statistically significantly improved with 6 months of agalsidase alfa treatment. In a single clinical study of agalsidase beta in children (n =16), skin Gb3 deposits and plasma Gb3 levels were reduced in boys. Differences exist in the administration and the safety profile of these two enzyme formulations. Follow-up of these cohorts and additional studies will be necessary to fully evaluate long-term efficacy of ERT in children with Fabry disease.
authors.affiliation: Department of Pediatrics, University Hospital Germans Trias i Pujol Badalona, Universitat Autònoma de Barcelona, Catalonia, Spain. gpintos.germanstrias@gencat.cat
authors.forename: Guillem
authors.initials: G
authors.lastname: Pintos-Morell
authors.forename: Michael
authors.initials: M
authors.lastname: Beck
mesh_terms: D001341:Autonomic Nervous System / Q000187:drug effects; D009202:Cardiomyopathies / Q000188:drug therapy; D002648:Child; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D000795:Fabry Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D005767:Gastrointestinal Diseases / Q000188:drug therapy; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000627:therapeutic use*; D007677:Kidney Function Tests; D008297:Male; D010146:Pain / Q000188:drug therapy; D011788:Quality of Life; D011994:Recombinant Proteins; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase; C459420:agalsidase beta