P23—New Guidelines for the Evaluation and Management of Fabry Disease in Children

Abstract

AND MANAGEMENT OF FABRY DISEASE IN CHILDREN A. Tylki-Szymanska; R.J. Hopkin; M. Banikazemi; D.P. Germain; M. Mauer; D.G. Warnock; and W.A. Wilcox Children’s Memorial Health Institute, Warsaw, Poland; Cincinnati Children’s Hospital, Cincinnati, Ohio; Columbia University College of Physicians and Surgeons, New York, New York; University of Versailles, Hopital Raymond Poincare, Garches, France; University of Minnesota, Minneapolis, Minnesota; University of Alabama at Birmingham, Birmingham, Alabama; and Medical Genetics Institute, Cedars-Sinai Medical Center, and Department of Pediatrics, UCLA School of Medicine, Los Angeles, California Introduction: Fabry disease (FD) is an X-linked lysosomal storage disorder, characterized by decreased or absent activity of lysosomal -galactosidase A. As a result of this enzyme deficiency, globotriaosylceramide (GL-3) and other glycosphingolipids accumulate within various tissues and eventually impair vital organ function, putting patients with FD at risk for developing renal failure, cardiovascular dysfunction, and stroke. The initial signs and symptoms of FD, including neuropathic pain in the extremities, hypohidrosis, angiokeratomas, and gastrointestinal discomfort, generally appear during childhood. More serious complications of FD can also occur during childhood, including proteinuria, valvular dysfunction, conduction abnormalities, left ventricular hypertrophy and arrhythmia. Aim & Methods: In view of the growing recognition that significant manifestations of FD can occur during childhood, an international group of physicians who have pediatric patients enrolled in the Fabry Registry developed a set of specific guidelines for assessing FD in children based on evidence from the Fabry Registry and published literature. Results: The general types of assessments recommended for children with FD include: medical/family history (gastrointestinal, pain, sweating; heat/cold intolerance); physical examination (vital signs, height, weight, blood pressure); patient-reported outcomes (quality of life, fatigue, pain); laboratory testing (measured glomerular filtration rate, albuminuria/proteinuria); diagnostic testing (enzyme activity, genotype); specialized laboratory testing (antibodies, plasma GL-3); ophthalmology (slit-lamp examination); other studies (audiologic evaluation, cranial magnetic resonance imaging [T1, T2, FLAIR], echocardiography and ECG); and treatment/medication history (enzyme-replacement therapy status, concurrent medications). Conclusions: This new Pediatric Minimum Recommended Schedule of Assessments will increase the medical community’s awareness of the burden of FD in children, assist with monitoring, and improve the outcome for these young patients.