A case of rapid progression of Fabry nephropathy with remarkable glomerulomegaly: a case report and mini literature review of weak response to enzyme replacement therapy (ERT)

Abstract

Background: Fabry disease is a rare X-linked hereditary disorder (Xq22) caused by a deficiency in alphagalactosidase (α-GAL) activity. This enzyme deficit results in the systemic accumulation of glycophospholipids, leading to multi-organ failure including the heart, kidneys, and brain. Enzyme replacement therapy (ERT) improves the prognosis of patients with Fabry disease. We describe a case showing progressive renal failure despite ERT.Case presentation: An 18-year-old obese male patient (body mass index (BMI) 29.9 kg/m 2 ) was admitted for detailed examination of mild degree hypertension (150/65 mmHg) and proteinuria occurring for 2 years prior to admittance. Laboratory tests revealed mostly normal kidney function (serum creatinine 0.5 mg/dL, estimated glomerular filtration rate 181 mL/min/m 2 ) with low α-GAL activity, a significant level of proteinuria (0.5-1.0 g/day), and the presence of mulberry cells in the urinary sediment. Renal biopsy demonstrated marked glomerulomegaly with diffuse vacuolization of the glomerular epithelial cells and focal segmental glomerulosclerosis. Electron microscopy revealed typical zebra bodies in the glomerular epithelial cells and effacement of foot processes of the epithelium. We could not find any cause of glomerulomegaly except for obesity. α-GAL gene analysis revealed a missense mutation in R301Q. Although ERT with agalsidase α was initiated, his renal function declined, and hemodialysis was initiated at 22 years of age. Conclusions:We present a case of rapid progression of Fabry nephropathy despite ERT. As with other renal diseases, obesity may aggravate the progression of Fabry nephropathy.

Role of Sphingolipid Signaling in Glomerular Diseases: Focus on DKD and FSGS

“…Another reported therapy targeting sphingolipids is enzyme replacement therapy (ERT), which currently represents a standard of therapy for Fabry disease, or lipid storage disease. In a recent case report of a Japanese man with FSGS and low activity of alpha-galactosidase (with mutation in M296I), ERT in association with immunotherapy with steroids and cyclosporine A [ 111 ] improved proteinuria levels, while in another case report of an obese male with histologically proven FSGS and low activity of alpha-galactosidase (with missense mutation in R310Q) no improvement in renal function despite ERT was described [ 112 ]. Thus, while ERT may be a very promising therapy for the treatment of lipid storage disease, its therapeutic potential in the treatment of patients with FSGS warrants further investigation.…”

Autopsy Findings of Heterozygous Fabry Disease with the Severe Phenotype: A Case Report

“…Additionally, we discussed why the patient's FD progressed so rapidly and if it was only caused by her hereditary factor. Reportedly, the role of acquired factors in patients with FD has been discussed [21]. In this case, the patient had obesity and dyslipidemia with a predominantly elevated low-density lipoprotein cholesterol level.…”

Clinical Diversity in Patients with Anderson-fabry Disease with the R301Q Mutation

“…As epigenetic abnormalities contribute to the development of certain cancers and autoimmune diseases, AFD may also be affected by epigenetic changes ( 15 ). In addition, acquired factors, such as hypertension, diabetes mellitus, and obesity, may contribute to the clinical manifestations of AFD, although this point remains to be fully elucidated ( 16 ). In the present study, due to the small number of patients, we were unable to address this point.…”