A 34-year-old male patient with Fabry disease (OMIM 301500) commenced enzyme replacement therapy (ERT) with Agalsidase alfa, with positive clinical response. Infusion reactions, initially mild and easily managed, commenced during his 13th infusion, and continued over the next 3 years. Severity of reactions subsequently increased despite very slow infusion, extended prophylactic medication and attempted desensitisation, requiring regular intensive care unit (ICU) admissions. Facial oedema and flushing, throat tightness, headache and joint pain typically occurred 4-36 h after completion of most infusions, responding rapidly to subcutaneous adrenaline. Low titre specific IgG seroconversion was noted at 12 months, with subsequent reversion to negative after 5 years, despite persistence of infusion reactions. Specific IgE and skin testing was negative. Trial of ERT product switch to Agalsidase-beta resulted in no improvement in reactions. At 5 years, ERT was ceased in the face of recurrent ICU readmissions. In the face of progressive clinical deterioration, he underwent tracheostomy to allow recommencement of ERT. Two years later, he has clinically improved on regular attenuated dose Agalsidase-beta, administered by slow infusion in a local hospital setting.
Case ReportDiagnosed in early childhood following proband identification, the patient endured severe disabling neuropathic pain and diarrhoea during childhood and adolescence, truncating his educational and employment opportunities. Serum and WBC a-Galactosidase (GLA) levels were measured as 0.03 nmol/min/mg (normal range 0.4-2.0), and genotype was identified as G128E. At the time of enzyme replacement therapy (ERT) commencement at age 34, his BMI was 20.1 kg/m 2 . His baseline pain was partially controlled on phenytoin, but frequent exacerbations occurred with infections and weather changes, sometimes requiring hospitalisation and narcotics. Diarrhoea was intractable, depression was significant, exercise capacity was limited to getting through his workday, and proteinuria had reached 800 mg/ day, although Cr-EDTA GFR, ECG and echocardiogram were normal.The first 12 infusions of ERT (Agalsidase alfa 0.2 mg/ kg/fortnight over 40 min) were uneventful. The 13th infusion, delayed for 3 months for logistic reasons, was complicated by facial flushing and subjective throat tightness, without change in temperature or blood pressure. Symptoms resolved rapidly with cessation of infusion, intravenous hydrocortisone and promethazine.All subsequent infusions were given under prophylaxis with hydrocortisone, combined variably with antihistamine (promethazine or certrizine), oral prednisolone and paracetamol. Over the next 3 years, reactions were occasional and mild, but accelerated in severity and frequency throughout JIMD Reports
