Heart disease Other symptoms too? FABRY DISEASE IN PATIENTS WITH UNEXPLAINED HEART CONDITIONS You have been given this brochure because your heart condition may be linked to Fabry disease, which is a rare, potentially serious, genetic disorder. 1,2 When patients present with signs and symptoms of serious or unexplained heart conditions, it can be an indicator of more complex underlying causes, one of which could be Fabry disease. 3,4 This brochure aims to answer some of the questions you may have about the causes, inheritance and management of Fabry disease. www.fabrydisease.info
WHAT IS FABRY DISEASE? Fabry disease (or Anderson-Fabry disease) is a rare inherited disorder caused by the lack of activity of an enzyme called alpha-galactosidase A, as the result of a gene change (mutation). 5 7 This enzyme is responsible for breaking down a fatty substance, known as globotriaosylceramide (Gb 3 ), in the cells of the body. 7,8 The build-up of Gb 3 deposits in the cells interferes with their normal functions, leading to progressive damage to the body and resulting in a wide range of symptoms and complications. 5,9 Heart disease can arise as the result of Gb 3 deposits, in the presence or absence of other symptoms. 10,11 HOW IS FABRY DISEASE LINKED TO MY HEART CONDITION? Heart problems are common in Fabry disease 5,12 and may become progressively worse with age. 13 As Gb 3 accumulates within the cells of the heart or the walls of the blood vessels that supply the heart, damage may occur. Heart problems due to Fabry disease may include heart enlargement; poorly functioning heart valves; irregular heartbeat; heart attack; or heart failure. 1,7 HOW CAN MY DOCTOR DIAGNOSE FABRY DISEASE? Fabry disease can be very difficult to distinguish from more common conditions due to the wide range of symptoms, and some patients spend many years without a correct diagnosis. 5,14 However, once your doctor suspects that you might have Fabry disease, a diagnosis can be made with a simple blood test. 15
WHAT ARE THE SYMPTOMS? Fabry disease is a complex condition and each person can be affected by it in a different way, and can therefore experience varying degrees and combinations of symptoms. 16 The most common signs and symptoms include: 17 Hearing problems such as ringing in the ear or hearing loss Impaired ability to sweat, which in turn causes frequent fevers and a low tolerance to heat or exercise Changes in the eye such as clouding of the cornea* Heart More serious problems affecting the heart, kidney and nervous system can typically be seen in older patients as the disease advances Stomach problems such as pain, nausea, vomiting or diarrhoea Small raised dark red spots (called angiokeratomas) on your skin Depression and fatigue Pain and burning sensation in hands and feet HOW CAN I MANAGE FABRY DISEASE? Your heart doctor (cardiologist) will continue your treatment for your heart problems and its related symptoms. manage the disease, if appropriate for you. Please consult your doctor or healthcare professional for further information. Fabry disease is not a curable condition, however, treatments are available to help *typically not affecting vision
HOW DOES FABRY DISEASE RUN IN THE FAMILY? Fabry disease is not contagious, but it is a hereditary condition that children can genetically inherit from their parents, 18 in a pattern illustrated below. Every cell in the human body contains chromosomes, which are thread-like structures carrying genetic information. Females have two X chromosomes in each cell (an X from each parent), and males have one X and one Y chromosome (an X from their mother and a Y from their father). The faulty gene causing Fabry disease is located on the X chromosome only. 6,7 This means that men carrying this gene are always affected by the disease, whereas women may not have symptoms, or their symptoms may be less severe or appear later in life. 19 An affected father (XY) will pass the faulty gene to all of his daughters, but none of his sons. 18 An affected mother (XX) will have a 50% chance of passing the faulty gene to her children (whether son or daughter). 18 Father Mother Father Mother XY XX XY XX XX XY XX XY XX XY XX XY X Faulty gene Due to the hereditary nature of Fabry disease, a diagnosis not only has important health consequences for you, but may also have implications for your family. If you are diagnosed disease, your doctor or healthcare professional will perform a family history evaluation (also called Pedigree analysis ) with you, to determine the risk of your family members having the condition. 20
References 1. DESNICK, RJ. et al. Fabry disease, an under-recognized multisystemic disorder: Expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 2003; 138(4): 338 46. 2. WEIDEMANN, F. et al. Long-term outcome of enzymereplacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications. J Intern Med 2013; 274(4): 331 41. 3. ELLIOTT, PE. Anderson-Fabry disease: an important differential diagnosis in patients with unexplained left ventricular hypertrophy. Heart Metab 2006; 33: 25 9. 4. NAGUEH, SF. Anderson-Fabry disease and other lysosomal storage disorders. Circulation 2014; 130(13): 1081 90. 5. MEHTA, A. et al. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry outcome survey. Eur J Clin Invest 2004; 34(3): 236 42. 6. SCHÄFER, E. et al. Thirty-four novel mutations of the GLA gene in 121 patients disease. Hum Mutat 2005; 25(4): 412. 7. DESNICK, RJ. A-Galactosidase A deficiency: Fabry disease. In: Scriver, CR. et al (eds). The metabolic and molecular bases of inherited disease. New York: McGraw-Hill; 2001: 3733 74. 8. BRADY, RO. et al. Enzymatic defect in Fabry s disease ceramidetrihexosidase deficiency. N Engl J Med 1967; 276(21): 1163 7. 9. BARBEY, F. et al. Efficacy of enzyme replacement therapy in Fabry disease. Curr Med Chem Cardiovasc Hematol Agents 2004; 2(4): 277 86. 10. SEYDELMANN, N. et al. Fabry disease and the heart. Best Pract Res Clin Endocrinol Metab 2015; 29(2): 195 204. 11. ENG, CM. et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 2006; 8(9): 539 48. 12. MORRISSEY, RP. et al. Cardiac abnormalities in Anderson- Fabry disease and Fabry s cardiomyopathy. Cardiovasc J Afr 2011; 22(1): 38 44. 13. LINHART, A. et al. Cardiac manifestations of Anderson- Fabry disease: results from the international Fabry outcome survey. Eur Heart J 2007: 28(10): 1228 35. 14. MARCHESONI, CL. et al. Misdiagnosis in Fabry disease. J Pediatr 2010; 156(5): 828 31. 15. GAL, A. et al. Toward a consensus in the laboratory of diagnostics of Fabry disease recommendations of a European expert group. J Inherit Metab Dis 2011; 34(2): 509 14. 16. RIES, M. and GAL, A. Genotype phenotype correlation in Fabry disease. In: Mehta, A. et al (eds). Fabry disease: perspectives from 5 years of FOS. Oxford: Oxford PharmaGenesis; 2006. Chapter 34. 17. GERMAIN, DP. Fabry disease. Orphanet J Rare Dis 2010; 5: 30. 18. GERMAIN, DP. General aspects of X-linked diseases. In: Mehta, A. et al (eds). Fabry disease: perspectives from 5 years of FOS. Oxford: Oxford PharmaGenesis; 2006. Chapter 7. 19. MEHTA, A. et al. Fabry disease: a review of current management strategies. Q J Med 2010; 103(9): 641 59. 20. LANEY, DA. and FERNHOFF, PM. Diagnosis of Fabry disease via analysis of family history. J Genet Counsel 2008; 17(1): 79 83. Shire International GmbH, Zählerweg 10, 6301 Zug, Switzerland Prepared and funded by Shire. INTSP/C-ANPROM/FAB/16/0006a(1) 11/2016