Abstract: SA-PO799
Complement-Mediated Hemolytic Uremic Syndrome due to CD46 Pathogenic Variant Unmasked by COVID-19
Session Information
- Genetic Diseases: Glomerulopathies - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Rosario-Falero, Jessica M., Tulane University School of Medicine, New Orleans, Louisiana, United States
- Yosypiv, Ihor V., Tulane University School of Medicine, New Orleans, Louisiana, United States
Introduction
Complement-mediated hemolytic uremic syndrome (HUS) is rare, with an estimated incidence of 10 cases per 1,000,000 children in the U.S. Only 5 to 10 percent of these cases are from CD46 gene variants. We report the case of a pediatric patient with a history of COVID-19 infection, presenting with severe thrombocytopenia, anemia and renal dysfunction who was found to have an extremely rare mutation in CD46.
Case Description
A previously healthy 3 y/o male presented with fever, abdominal pain, anorexia, and dark colored urine for 5 days. He had recent history of COVID-19. Mother denied him having had diarrhea. He had no prior history of kidney diseases and family history was non-contributory. Physical exam was remarkable for scleral icterus, and diffuse abdominal tenderness. Laboratory workup showed anemia (hemoglobin: 6.4 g/dL), thrombocytopenia (21 x 103μL), acute kidney injury (BUN 102 mg/dL, plasma creatinine 2.45 mg/dL), and schistocytes in peripheral blood smear. He also had hyperbilirubinemia (total bilirubin 2.4 mg/dL, direct bilirubin 1.7 mg/dL), elevated lactate dehydrogenase (2,991 U/L), gross hematuria and nephrotic range proteinuria (urine protein to creatinine ratio 4.6 mg/mg). Clinical picture was consistent with thrombotic microangiopathy. Further workup revealed a negative direct antiglobulin test, normal complement C3 and C4 levels, and normal ADAMTS13 activity level. Stool was negative for Shiga toxin. We suspected this was a case of atypical HUS (aHUS) in the setting of recent viral infection (COVID-19). Genetic panel for aHUS was ordered, and patient was started on Eculizumab (human anti-C5 monoclonal antibody).
Discussion
Patient’s clinical status significantly improved after the first dose of Eculizumab. Platelet count and BUN normalized. Hemoglobin and plasma creatinine improved significantly (8.5 g/dL and 0.8 mg/dL respectively). LDH was down trending by the time of discharge (1238 U/L). Genetic panel revealed an extremely rare heterozygous nonsense variant in exon 5 of the CD46 (c.486T>A, p.Cys162Stop) confirming our working diagnosis.
This case demonstrates the importance of prompt recognition of aHUS, early genetic/functional testing for complement-mediated aHUS and early initiation of Eculizumab to reduce the risk of permanent kidney damage. It also shows that COVID-19 infection may act as trigger for complement-mediated aHUS.