ESPN 51th Annual Meeting

ESPN 2018


 
Complement factor H mutation in C3 glomerulopathy with initial presentation as hemolytic uremic syndrome: A case report
NURDAN YILDIZ 1 MEHTAP SAK 1 ISIN KILICASLAN 2 NESLIHAN CICEK 1 IBRAHIM GOKCE 1 HARIKA ALPAY 1

1- MARMARA UNIVERSITY MEDICAL SCHOOL DIVISION OF PEDIATRIC NEPHROLOGY
2- ISTANBUL UNIVERSITY ISTANBUL MEDICAL SCHOOL, DIVISION OF PATHOLOGY
 
Introduction:

Dysregulation of the alternative complement cascade plays a crucial role in the pathogenesis of atypic hemolytic uremic syndrome(HUS) and complement mediated membranoproliferative glomerulonephritis (MPGN)/C3 glomerulopathy(C3G). Many cases who were initially diagnosed as having different type of glomerulonephritis later developed aHUS or aHUS and C3G developed concurrently.

Here, we present a patient that initially diagnosed as diarrhea (+)HUS and developed MPGN four years later during the follow-up, and we intend to discuss possible common pathophysiological mechanisms of these diseases.

Material and methods:

 Case report

Results:

 Case:A 17 year-old boy admitted to our clinic with hematuria and proteinuria. The past medical history revealed that he was diagnosed as diarrhea (+)HUS, treated by peritoneal dialyses for three months and recovered with normal renal functions when he was 1 year old. At the age of five, he admitted on the same clinic with swelling on the face and legs. Laboratory investigation revealed hypoalbuminemia, hyperlipidemia and nephrotic range proteinuria. He was diagnosed as nephrotic syndrome and kidney biopsy was performed due to steroid resistance. Light and electron microscopic examination of the renal tissue showed MPGN and immunofluorescence staining demonstrated marked granular mesangial C3 deposition. Glomerular C1q and immunoglobulins were negative. He admitted to our clinic with microscopic hematuria and proteinuria at the age of six. He was on alternate day steroid therapy and his serum creatinine was 0.82 mg/dL, albumin 5 g/dl, GFR 62.4 mg/dk/1.73 m2 and 24-hour urine protein excretion was 59.8 mg/m2/h. Serologic tests were negative for anti-nuclear antibodies, cytoplasmic anti-neutrophil antibodies, hepatitis B, hepatitis C and human immunodeficiency viruses, and C3 and C4 levels were normal. During the follow-up, his serum creatinine and albumin levels were stable and proteinuria regressed to 10-15 mg/m2/h on oral prednisolone and angiotensin converting enzyme inhibitor therapy. In 2015, based on new literature, we reevaluated the biopsy findings and diagnosed him as C3G. Genetic testing revealed heterozygote c.A3148T mutation in complement factor H gene which is associated with C3G. After the first episode, the patient did not have any HUS attack, proteinuria remained in nephritic range and serum albumin in normal range,however, serum creatinine increased to 1.75 mg/dl.

Conclusions:

Our case confirms that mutations in the CFH gene may be responsible for two distinct diseases, aHUS and MPGN/C3G, which are associated with alternative complement pathway defect. A transition between these diseases can occur in the same patient and support common pathophysiology.