A Unique Presentation of Fabry Disease with Progressive Bilateral Hearing Loss

Introduction: Fabry disease is the second most prevalent lysosomal storage disease and can affect multiple organs, including the kidneys and the vertebrobasilar system. Fabry Nephropathy presents with proteinuria and progressive renal failure. We present a case of a patient who presented with nephrotic range proteinuria and progressive hearing loss, who was found to have Fabry disease. Case Description: A 32-year-old male with a past medical history of progressive bilateral hearing loss, initially presented for evaluation of nephrotic range proteinuria. He attributed his hearing loss to a traumatic ear injury and reports "compensating with his other ear". He also reports a history of acroparasthesias in his hands triggered by cold weather, generalized fatigue, and a single episode of self-limiting hematuria which occurred a year prior. The patient was referred for a UACR of 3.2g with Creatinine within normal range and GFR>60. Given the concern for Alport disease, a renal biopsy was performed. The biopsy demonstrated numerous podocyte inclusions concerning for Fabry disease. There was also evidence of glomerulomegaly, thickened GBM, and segmental sclerosis likely due to hyperfiltration/proteinuria. Genetic testing done was positive for GLA mutation and enzyme testing showed deficiency in alpha galactosidase, confirming the diagnosis of Fabry disease. The patient was started on Fabrazyme infusions. Proteinuria (UPCR of 0.5g), paresthesia, and fatigue all improved significantly after starting enzyme replacement therapy. The patient reported improvement in hearing loss, but still required the use of hearing aids. Discussion: This is a case of Fabry disease with an atypical presenting symptom. Fabry disease is an X-linked disorder and results in accumulation of globotriaosylceramide (Gb3) within lysosomes in a wide variety of cells. Multiple organs, including the kidneys, can be affected. Proteinuria and progressive renal decline occur secondary to accumulation of Gb3 in the glomeruli, distal tubule, and vascular smooth muscle cells. It is essential to keep a high index of suspicion of unexplained nephrotic range proteinuria accompanied by paresthesia in patients. Our case demonstrated the importance of early diagnosis with kidney biopsy leading to resolution of proteinuria and symptoms after initiation of enzyme replacement.