title: Enzyme replacement therapy in two Japanese siblings with Fabry disease, and its effectiveness on angiokeratoma and neuropathic pain.
abstract: Enzyme replacement therapy (ERT) for Fabry disease does not show a clear benefit in angiokeratoma. We describe two Japanese siblings with Fabry disease, who were diagnosed when angiokeratomas were found on the older sibling at the age of 13 years. Neither of the boys complained of pain, while both suffered from hypohidrosis. We evaluated the safety and efficacy of ERT with recombinant human agalsidase alfa (Replagal®, Dainippon-Sumitomo Pharma. Co., Osaka, Japan) in these siblings over a 5-year period. In both siblings, sweating was observed 3 months after the initiation of ERT, which motivated them to adhere to ERT. Pain sensation was regained after 12 to 36 months of ERT, followed by a decrease after 48 to 60 months. Angiokeratomas on the lateral side of the knee of the older sibling partially disappeared after 48 months of ERT. Although the height of both siblings at baseline was lower than the corresponding average age-related heights in the normal Japanese population, during ERT they were within, or close to, the average +1 standard deviation in the non-Fabry population. Their growth rate seemed to indicate catch-up growth. Other clinical symptoms were maintained at baseline levels. Immunoglobulin G anti-agalsidase alfa antibodies were not detected in both sibling during ERT, and no infusion-associated reaction was observed. The treatment was generally well tolerated. ERT was a safe and effective treatment for angiokeratoma and neuropathic pain for these two siblings with Fabry disease.
authors.affiliation: Department of Pediatrics, Okayama Medical Center, Okayama, Japan. Electronic address: fuhkun@okayama3.hosp.go.jp.
authors.forename: Mahoko
authors.initials: M
authors.lastname: Furujo
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kubo
authors.forename: Masahisa
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Toya
authors.initials: T
authors.lastname: Ohashi
mesh_terms: D000293:Adolescent; D000794:Angiokeratoma / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D056947:Enzyme Replacement Therapy / Q000009:adverse effects; D000795:Fabry Disease / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D010375:Pedigree; D035781:Siblings; D016896:Treatment Outcome; D014281:Trihexosylceramides / Q000097:blood / Q000652:urine; D000519:alpha-Galactosidase / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase
keywords: Agalsidase alpha; BPI; Brief Pain Inventory; Child; Cre; EF; ERT; Enzyme replacement therapy (ERT); Fabry disease; GSL; Gb3; LVMI; MRI; creatinine; eGFR; ejection fraction; enzyme replacement therapy; estimated glomerular filtration rate; globotriaosyl ceramide; glycosphingolipids; left ventricular mass index; magnetic resonance imaging