One explanation could be that Fabry patients often have a low reaction to insect bites, probably part of an autonomic dysfunction [22]. reintroduced, leading to a second anaphylactoid shock episode. Enzyme replacement therapy was stopped and the patient was treated with symptomatic therapy only. This case was referred to the pharmacovigilance department. CONCLUSION The negativity of immunological tests Hydroquinidine (specific anti-agalsidase IgE antibodies and skin tests) does not rule out the risk of repeated anaphylactoid shock following agalsidase infusion. Keywords: agalsidase, enzyme therapy, Fabry disease, IgG antibodies, pharmacovigilance WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Fabry disease is an X-linked lysosomal storage disorder related to -galactosidase A deficiency. Two enzyme replacement therapies were approved by the European Medicines Agency in 2001: agalsidase-alfa and agalsidase-beta. Patients with Fabry disease and treated with agalsidase-alfa or -beta can develop antibodies against the protein infused. IgG antibodies against agalsidase-alfa and IgG and IgE antibodies against agalsidase-beta were previously described. WHAT THIS STUDY ADDS Despite two successive treatments with agalsidase in our patient, kidney function declined. Cross-reactivity between the two enzymes could be demonstrated. Negative IgE antibodies and skin tests results do not necessarily equate with safety and the ability to continue with enzyme replacement therapies. Fabry disease (FD) (OMIM 301 500) is an X-linked metabolic disorder characterized by a defect in the degradation of glycosphingolipids with terminal -galactose residues that leads to progressive intralysosomal accumulation of globotriaosylceramide (GL-3) in various tissues [1]. The underlying cause is a mutation in the gene encoding the lysosomal enzyme -galactosidase A (alphaGAL). Manifestations of the disease occur mostly in affected hemizygous men but also in heterozygous (carrier) women [2C4]. Severe morbidity is caused by heart failure, arrhythmias, stroke or end-stage renal disease. In the absence of enzyme replacement therapy (ERT), life expectancy is about 50 years for men and 70 years for women. Case report A 40-year-old male patient was referred in 2004 because of left foot oedema. He had experienced acroparaesthesia and hypohidrosis from the age of eight. Physical examination showed distal limb lymphoedema, angiokeratoma and telangiectasies. Blood pressure was normal. Because of such symptoms and familial history C a brother also affected C FD was suspected. Ophthalmological examination revealed cornea verticillata. Echocardiography revealed left ventricular hypertrophy with no diastolic dysfunction. Brain magnetic resonance imaging revealed high signal on T2-weighted images in the posterior part of both thalami (pulvinar), a typical finding of FD [5]. Hydroquinidine Measured glomerular filtration rate (GFR) by Iohexol method was 63 ml min?1 1.73 m?2 and the daily proteinuria level was 1 g. Hydroquinidine A renal biopsy was not performed. Chest X-ray revealed two dorsal vertebral fractures. Dual energy X-ray absorptiometry confirmed osteoporosis with a T score below ?4 SD in both lumbar and femoral sites. FD was confirmed by a leucocyte-specific activity of -galactosidase A of 2 nmol h?1 mg?1 of protein (normal range 25C55). The missense mutation D266E in exon 5 of -galactosidase A gene has been identified. Successive GFR measurements, daily proteinuria and titres of antibodies against ERT are summarized in Figure 1. Open in a separate window Number 1 Successive glomerular filtration rate (GFR) measurements, daily proteinuria and titres of antibodies. GFR (ml/min/1.73 m2) (); Proteinuria (g/day time) (); lgG Antibodies level (titre) (?) Ramipril 1.25 mg dayC1 was started. Enzyme alternative therapy was initiated in May Rabbit Polyclonal to SRY 2005. The patient received an agalsidase-alfa infusion of 0.2 mg kgC1, biweekly. Hydroquinidine In July 2005, during the fifth infusion, the patient had an acute reaction with bronchial spasm, which was treated with intravenous (i.v.) corticosteroids and antihistaminic therapy. The patient then received premedication therapy with 60 mg of i.v. methylprednisolone and 5 mg of i.v. dexchlorpheniramine before the following infusions and tolerance was good. In June 2006, GFR was unchanged at 60 ml min?1 1.73 m?2. Antibodies against agalsidase-alfa were bad. ERT was pursued with premedication therapy, but the patient suffered sweats, asthenia, dysaesthesia in hands, and peripheral vasoconstriction at the end of each infusion. In July 2007, serum IgG antibodies against agalsidase-alfa were positive (titre 200; average < 100). Agalsidase-alfa infusions were continued biweekly.
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