SP012COMPLETE ELIMINATION OF RENAL GLYCOSPHINGOLIPID DEPOSITION BY 3 YEARS OF TREATMENT WITH AGALSIDASE BETA IN A BOY WITH FABRY DISEASE

Abstract

Introduction: Enzyme replacement therapy (ERT) using agalsidase is a unique and effective therapy against Fabry disease. However, early diagnosis is difficult if there is a lack of family history. A delay in diagnosis often results in irreversible organ damage, but initiation of ERT in children or young adults without apparent organ involvement is still controversial. We report here the clinical course and renal pathological findings in a boy with Fabry disease before and 3 years after ERT. Results: A 10-year-old boy was referred to our hospital because of pain on the soles of his feet since 7 years old. The pain was intermittent, but sometimes endurable, and disturbed his school life and sleep. Despite many consultations with pediatricians and orthopedists, he was undiagnosed. However, we suspected Fabry disease and performed biochemical and genetic analysis. His serum globotriaosylceramide (GL3) level was markedly increased. His alpha-galactosidase A activity was also markedly reduced (2.5 AgalU; normal (male) <17 AgalU) because of a truncated M1T mutation in the GLA gene. We found that he also suffered from hypohidrosis and angiokeratoma on his foot and hips. Although he showed neither a decreased eGFR nor microalbuminemia, his renal biopsy showed typical features of Fabry disease, with GL3 accumulation in podocytes, endothelial cells, mesangial cells, and tubules. Partial foot process effacement of podocytes was characteristic, suggesting podocytopathy. We treated him with 1.0 mg/kg of agalsidase beta, pregabalin, and carbamazepine biweekly. Three years after initiation of ERT, the pain on his soles had disappeared and his hypohidrosis had improved. His daily and school activities favorably compared with healthy children of the same age. Renal biopsy showed complete elimination of GL3 from podocytes, endothelial cells, mesangial cells, and tubules. Foot process effacement had also disappeared. Conclusion: Appropriate timing of initiation of ERT is still controversial. However, a recent report on a 5-year high dose of ERT (0.4-1.0 mg/kg/2W) showed a marked reduction in renal GL3 accumulation, including podocytes, in children or young adults. Our patients also showed that early indication of high-dose ERT for male children with truncated mutation might improve their prognosis and quality of life. Therefore, awareness of early clinical signs by pediatricians and orthopedists could be indispensable for early diagnosis and treatment.