Immune-Negative Focal Segmental Nephrotic Syndrome Disclosing a Novel Mutation of Autosomal Dominant Alport’s in a Female

Abstract

Background: Alport syndrome (AS) is a rare genetic disease characterized by progressive renal failure due to glomerulopathy, variable high-frequency sensorineural deafness, and variable ocular anomalies. The case : A 33-year-old woman was referred for evaluation of progressive lower limb oedema for 2 weeks following 1 week after receiving the second dose of the Oxford–AstraZeneca COVID19 vaccine. She had hypertension, hematuria, and nephrotic syndrome with serum albumin at 19 g/L and 6 g/day proteinuria. Her parents did not have renal disease. She had no clinical, laboratory, radiological, or serological evidence of autoimmune disease or infections. Kidney biopsy showed focal and segmental glomerulosclerosis with negative immunostains, yet electron microscopy showed a basket-weave appearance of the glomerular basement membrane. Genetic testing disclosed an autosomal pattern with a novel pathogenic mutation in COL4A3 c.3829G>A p.(Gly1277Ser), and COL4A5 had a c.4436C>T sequence change, replacing alanine with valine at codon 1479 protein (p.Ala1479Val). She did not respond to 2 months of therapy with diet, Losartan, and diuretics (Furosemide and Spironolactone). Since acute nephrotic state was present, Mycophenolate mofetil and Tacrolimus were selected for treatment. By 1 month later, her proteinuria decreased to 1.9 g/day, and serum albumin increased to 34 g/L. By 5 months (3 months after Mycophenolate mofetil and Tacrolimus therapy), proteinuria reached 870 mg/day and serum albumin reached 39 g/L. Hence, these were replaced by yearly Rituximab infusions. Up to 2 years of follow-up, the patient remained clinically stable and with normal serum creatinine, albumin, and proteinuria at 530 mg/day. Conclusion : A new-onset and novel mutation of AS can present with nephrotic syndrome after a trigger that was amenable to immunosuppressive therapy. The genetic disorder may not be cured, yet autoimmunity may have a role in its acute flares in certain phenotypes.