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CONTEXT. Fabry disease is an X-linked multisystem disorder. Enzyme-replacement therapy in adults has limited efficacy in treating major sequelae of advanced Fabry disease, such as kidney failure or stroke. This prompted a study of the safety and efficacy of enzyme replacement at an earlier stage of Fabry disease. OBJECTIVES. Our purpose with this work was to evaluate safety and to explore efficacy of enzyme treatment with agalsidase alfa in pediatric patients with Fabry disease. METHODS. We conducted a 6-month open-label study at 3 tertiary care centers with 24 children (19 boys and 5 girls) with a mean age of 11.8 (range: 6.5-18) years, to examine safety parameters, including infusion reactions and antiagalsidase alfa antibodies. RESULTS. Agalsidase alfa was well tolerated, and all of the patients completed the study. Six boys and 1 girl had mild-to-moderate infusion reactions. One boy developed transient immunoglobulin G antibodies against agalsidase alfa. The boys showed a significant reduction in plasma globotriaosylceramide on treatment. Mean estimated glomerular filtration rate, cardiac structure, and function were normal and did not change over 26 weeks. Heart rate variability, as determined by 2-hour ambulatory monitoring, was decreased in the boys compared with the girls at baseline. All indices of heart rate variability improved significantly in the boys. Three patients with anhidrosis, as determined by quantitative sudomotor axon reflex testing, developed sweating. Six of 11 patients could reduce or cease their use of antineuropathic analgesics. CONCLUSIONS. Enzyme replacement with agalsidase alfa was safe in this study. The exploratory efficacy analysis documented increased clearance of globotriaosylceramide and improvement of autonomic function. Prospective long-term studies are needed to assess whether enzyme replacement initiated early in patients with Fabry disease is able to prevent major organ failure in adulthood. Key Words lysosomal storage disease, therapy, stroke, pediatric, cardiac disease Abbreviations FD--Fabry disease GALA--[alpha]-galactosidase A [Gb.sub.3]--globotriaosylceramide ERT--enzyme-replacement therapy QoL--quality of life eGFR--estimated glomerular filtration rate mean RR--mean beat-to-beat interval SDNN--SD of all normal beat to normal beat intervals SDNN-l--mean of the SD of all filtered RR intervals for all 5-minute segments of the analysis SDANN-i--SD of the means of all filtered RR intervals for all S-minute segments of the analysis r-MSSD--square root of the mean of the sum of squares of differences between adjacent filtered RR intervals for the length of the analysis pNN50--percentage of differences between adjacent filtered RR intervals that are >50 milliseconds for the whole analysis HUI--Health Utility Index QSART--quantitative sudomotor axon reflex test BPI--brief pain inventory Ig--immunoglobulin LVM--left ventricular mass LVM/h--left ventricular mass indexed for height, FABRY DISEASE (FD) is a lysosomal storage disease caused by a deficiency of the activity of the lysosomal enzyme [alpha]-galactosidase A (GALA), resulting from mutations of the [alpha]-galactosidase A gene [...]

Abstract Fabry disease is a lysosomal storage disorder with kidney involvement. The initial manifestation of kidney disease is often impaired urinary concentrating ability in adolescence or young adulthood. We describe [...]

Fabry's disease is an inherited enzyme disorder that affects males, causing numbness or tingling in the hands and feet, warty growths on the skin, corneal opacity, and an inability to sweat normally. The heart muscle is also involved, with certain individuals experiencing angina pectoris (chest pain caused by transient reductions in blood flow to the heart) and abnormal electrocardiogram results. The disease is progressive, and complications involving the heart, kidneys, and blood circulation in the brain are common. After kidney dialysis became available, these patients began to live longer than the previous average of 41 years. Atypical variants of the disease include one in which only the heart muscle (myocardium) is affected. The case of a 54-year-old man with angina is presented, and a genetic study of the patient and members of his family is detailed. Fabry's disease can manifest itself in a variety of ways, with patients having only one or any combinations of symptoms. In one case, a man with no symptoms at all was identified accidentally. In the case presented in this article, symptoms of Fabry's disease only occurred after most patients would have died of the disease, and were probably the result of a mild variant form of the disease. The physiology of the mechanism of the variant is discussed. Patients with cardiac symptoms such as angina or exercise intolerance, and who have no underlying coronary artery disease or other evident cause, usually remain undiagnosed. In such cases, Fabry's disease should be considered. (Consumer Summary produced by Reliance Medical Information, Inc.)

Byline: Leyla Tumer (1), Fatih S. Ezgu (1), Alev Hasanoglu (1), Buket DalgA+-c (2), Sevcan A. Bakkaloglu (3), Leyla MemiA (4), AyAe Dursun (4) Keywords: Fabry disease; Celiac disease; Enzyme therapy Abstract: We present a patient with Fabry disease with remarkable diagnostic findings and gluten-sensitive enteropathy. An 11-year-old girl was admitted to hospital with weight loss, anorexia, nausea, vomiting, flank pain, acroparesthesia, and painful extremities. Her mother had end-stage renal failure secondary to Fabry disease. On physical examination, she had growth retardation. Ophthalmological examination showed characteristic whorl-like corneal opacities and Fabry disease was confirmed with low [alpha]-galactosidase A ([alpha]-gal A) activity. Her painful attacks were treated with carbamazepine, but vomiting and nausea continued. Laboratory studies revealed positive serum anti-endomysium and anti-gliadin antibodies. Small intestinal biopsy showed subtotal villous atrophy compatible with gluten-sensitive enteropathy. Following treatment with a gluten-free diet, her gastrointestinal symptoms completely disappeared within a few weeks and then she had catch-up growth. In her long-term follow-up, proteinuria appeared and renal involvement was confirmed by characteristic renal biopsy findings. Following these clinicopathological findings, enzyme replacement therapy was started. In conclusion, although heterozygous females can be asymptomatic or are expected to have a mild course of the disease, a severe clinical course in our patient in the 2nd decade is of particular interest. In addition, Fabry disease occurring with gluten-sensitive enteropathy, a very rare co-existence, is emphasized. Author Affiliation: (1) Department of Pediatric Metabolism and Nutrition, Faculty of Medicine, Gazi University, Besevler, Ankara 06500, Turkey (2) Department of Pediatric Gastroenterology, Faculty of Medicine, Gazi University, Besevler, Ankara 06500, Turkey (3) Department of Pediatric Nephrology, Faculty of Medicine, Gazi University, Besevler, Ankara 06500, Turkey (4) Department of Pathology, Faculty of Medicine, Gazi University, Besevler, Ankara 06500, Turkey Article History: Registration Date: 25/02/2004 Received Date: 19/08/2003 Accepted Date: 13/02/2004 Online Date: 15/04/2004

Fabry's disease is an X linked inborn error of metabolism due to deficient activity of the lysosomal enzyme α galactosidase A. Previously unrecognised Fabry's disease presenting in a 52 year [...]

Byline: Amar. Surjushe, Saurabh. Jindal, Prajct. Sao, Sudhir. Medhekar, D. Saple Sir, Anderson-Fabry's disease also known as angiokeratoma corporis diffusum universale, is a disorder caused by the deficiency of the [...]

Fabry's disease is an inherited disorder of glycolipids (sugars linked to fatty molecular structures). Enzymes, specific proteins with singular activities, are required to build up and break down glycolipids, and deficiency of one such enzyme in Fabry's disease leads to glycolipid deposits in various organs, including the cardiovascular system. A number of heart dysfunctions have been found in Fabry's disease, but relatively few cases of dysfunction or block in the electrical conduction system which forms the pacemaker system have been reported. Two cases of Fabry's disease in two brothers are reported in which both had complete atrioventricular block (block between the pacemaker cells in the upper chamber and the lower pumping chamber). The men, who were 41 and 46 years old, had half the normal pulse rate. One brother also had abnormal pacemaker cell function as well. Both brothers were treated by implantation of permanent artificial pacemakers. Biopsies of heart tissue showed fatty deposits, and such deposits in the cells of the conduction system were apparently responsible for the heart dysfunction. (Consumer Summary produced by Reliance Medical Information, Inc.)

Angiokeratoma corporis diffusum (ACD), also called Fabry-Anderson's disease, is a very rare (about 3 cases per 1,000,000 births) inherited disease characterized by a deficiency in levels of an enzyme necessary to metabolize the carbohydrate breakdown products of cells. This deficiency eventually manifests itself with pain in the hands and feet, skin discolorations and growths, kidney dysfunction, and heart and brain damage. A case is presented of a patient with a history of lack of appetite, vomiting, weight loss, loose stools, and swollen ankles. Further examination indicated tiny brown raised spots on the abdomen, thighs, and buttocks. Urine tests, blood chemistry, microscopic examination of stools, and gastrointestinal tests failed to yield a conclusive diagnosis. Dental information revealed that two years previously, all teeth had been replaced by crowns to cover mottled yellow-brown enamel which was severely worn; other dental structures were normal. Conclusive diagnosis of ACD was made by measuring decreased serum levels of the enzyme x-galactosidase A. Investigation of family history revealed that a younger brother also suffered from ACD, with mild symptoms of pain in the extremities. In addition, the dental findings led to a diagnosis of hypoplastic amelogenesis imperfecta, another X-linked inherited disease. This is the first case of ACD reported with anorexia, weight loss, and diarrhea developing prior to limb pain onset. (Consumer Summary produced by Reliance Medical Information, Inc.)