Abstract: TH-PO508
Influenza B Triggering Atypical Hemolytic Uremic Syndrome (aHUS) in a Patient with Cobalamin C (CblC) Disease Carrier State and a Complement Factor H (CFH) Mutation
Session Information
- Genetic Kidney Diseases: Genotypes and Phenotypes in Cases
October 24, 2024 | Location: Exhibit Hall, 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
- Aponte Becerra, Laura, Yale University, New Haven, Connecticut, United States
- Moeckel, Gilbert W., Yale University, New Haven, Connecticut, United States
- Gunasekaran, Deepthi, Yale University, New Haven, Connecticut, United States
Introduction
AHUS is driven by abnormalities in genes coding for alternative complement pathway regulators triggering increased activity of the membrane attack complex. This causes endothelial damage, platelet adhesion and formation of microthrombi with subsequent thrombocytopenia, intravascular destruction of erythrocytes and acute kidney injury; termed thrombotic microangiopathy (TMA). We report a rare environmental trigger for aHUS in a patient with rare mutations in cobalamin uptake and CFH gene.
Case Description
A 59-year-old woman presented with upper respiratory symptoms and tested positive for Influenza B. Laboratory showed AKI, thrombocytopenia, hemolytic anemia with schistocytes and nephrotic range proteinuria. Creatinine at admission was 2.14mg/dL (from a normal baseline) and peaked at 8.67mg/dL with hyperkalemia requiring hemodialysis. C3 was low. C4, ADAMTS13 activity and Vitamin B12 were normal and methylmalonic acid level was mildly elevated. Acute kidney injury progressed and patient required initiation of hemodialysis. Kidney biopsy showed lobular accentuation of glomeruli, increased matrix deposition, karyorrhectic debris and red blood cell fragments in the mesangium and fibrinoid necrosis of an arteriole. Eculizumab was initiated and six days later renal function recovered, and dialysis was discontinued. Genetic testing revealed heterozygous p. Arg161Gly missense variant in the metabolism of cobalamin associated C (MMACHC gene) and heterozygous p. Thr724Lys missense variant in the CFH gene classified as a variant of unknown significance.
Discussion
MMACHC gene mutations cause autosomal recessive methylmalonic aciduria and homocystinuria (CblC disease) which rarely presents as aHUS. CblC disease is usually reported in children and none in the carrier state. Additional CFH high-risk haplotype and environmental factors increased the risk for aHUS in this case, with influenza being a known trigger but influenza B being very rare. This case highlights the importance of suspecting aHUS in older adults with identifiable triggers and low threshold to initiate complement blockade.