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Kidney Week

Abstract: SA-PO591

A Rare Genetic Cause of Steroid Resistant Nephrotic Syndrome

Session Information

  • Pediatric Nephrology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1800 Pediatric Nephrology

Authors

  • Carter, Jessamyn S., Nationwide Children's Hospital, Columbus, Ohio, United States
  • Spencer, John David, Nationwide Children's Hospital, Columbus, Ohio, United States
Introduction

MIRAGE syndrome, named for Myelodysplasia, Infection, growth Restriction, Adrenal hypoplasia, Genital phenotypes, and Enterpoathy, is a rare genetic disorder caused by autosomal dominant mutations in SAMD9 and which is sometimes associated with adaptive monosomy 7 leading to myelodysplasia. However, there is significant genotypic and phenotypic variation with an increase in identified mutations and presentations in recent years. We present here a case of focal segmental glomerulosclerosis in a patient with MIRAGE syndrome associated with a novel SAMD9 mutation.

Case Description

A 3 year old boy with history of intrauterine growth restriction, cryptorchidism, and intermittent thrombocytopenia presented for persistent proteinuria (urine protein:creatinine ratio, or UPCR, of 3.4) with normal serum albumin. Renal biopsy showed segmental sclerosis in 2 out of 20 glomeruli, and he completed a prednisone course with no improvement of proteinuria. He was then started on enalapril and spironolactone with improvement of UPCR to 1 and has remained on renin-angiotensin-aldosterone system blockade since that time for management of his proteinura. His hematologic course progressed to myelodysplastic syndrome with transient monosomy 7 and he underwent bone marrow transplant at age 8. That year, while on tacrolimus from BMT, he developed edema and hypoalbuminemia prompting repeat renal biopsy which again showed focal segmental glomerulosclerosis. Immunosuppression with curcumin was given with improvement in UPCR from 4.4 to 1.6 initially but with recurrent increase over the next two years. He has since received no other immunosuppression and maintains on lisinopril and spironolactone with variable but persistent proteinuria and intermittent episodes of edema. UPCR was 6.8 during most recent follow up at age 15.

Discussion

MIRAGE syndrome is a rare but increasingly recognized genetic disease impacting many organ systems. The immunologic and hematologic manifestations are most notable because of potential lethality, but scattered evidence suggests MIRAGE syndrome can be associated with glomerular disease. Though not definitive, people with MIRAGE syndrome may have structural anomalies in the endosomal system, which could trigger dysfunctional endocytosis in podocytes and lead to proteinuria.