Postoperative Atypical Hemolytic Uremic Syndrome Associated with Complement C3 Mutation

Atypical hemolytic uremic syndrome (aHUS) can be distinguished from typical or Shiga-like toxin-induced HUS. The clinical outcome is unfavorable; up to 50% of affected patients progress to end-stage renal failure and 25% die during the acute phase. Multiple conditions have been associated with aHUS, including infections, drugs, autoimmune conditions, transplantation, pregnancy, and metabolic conditions. aHUS in the nontransplant postsurgical period, however, is rare. An 8-month-old boy underwent surgical repair of tetralogy of Fallot. Neurological disturbances, acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia developed 25 days later, and aHUS was diagnosed. Further evaluation revealed that his complement factor H (CFH) level was normal and that anti-FH antibodies were not detected in his plasma. Sequencing of his CFH, complement factor I, membrane cofactor protein, complement factor B, and thrombomodulin genes was normal. His ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin-1 repeats 13) activity was also normal. However, he had a potentially causative mutation (R425C) in complement component C3. Restriction fragment length polymorphism analysis revealed that his father and aunt also had this mutation; however, they had no symptoms of aHUS. We herein report a case of aHUS that developed after cardiovascular surgery and was caused by a complement C3 mutation.

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Novel Complement Factor H mutation, a case report of atypical hemolytic uremic syndrome

Case Reports in Internal Medicine ◽

10.5430/crim.v4n2p13 ◽

2017 ◽

Vol 4 (2) ◽

pp. 13 ◽

Cited By ~ 1

Author(s):

Rodrigo Andrés Sepúlveda ◽

Rodrigo Tagle ◽

Aquiles Jara

Keyword(s):

Renal Failure ◽

Hemolytic Uremic Syndrome ◽

Alternative Pathway ◽

Atypical Hemolytic Uremic Syndrome ◽

Factor H ◽

Complement Factor H ◽

Complement Factor ◽

Severe Renal Failure ◽

Uremic Syndrome ◽

I Factor

Atypical hemolytic uremic syndrome (aHUS) is a rare but catastrophic disease. It is characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. When the aHUS is primary, the cause is due to mutations in proteins that regulate the alternative pathway of complement, such as Factor H, Factor I, Factor B, C3, Membrane Co-Factor Protein and Thrombomodulin. Usually primary aHUS is associated with other amplifiers complement factors. We present a case of aHUS in a 25-year-old female patient; she presented with malignant hypertension and severe renal failure. After a widespread study, the etiology of the aHUS was a mutation in the complement factor H, not previously described in the literature (p.Tyr1177His). After treatment with Eculizumab (C5 inhibitor monoclonal antibody), she recovered renal function with not hemodialysis requirements.

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Phenotypic manifestation of homozygous partial deletion of the chromosome 1 segment spanning CFHR3 region

Medical Immunology (Russia) ◽

10.15789/1563-0625-pmo-1901 ◽

2020 ◽

Vol 22 (3) ◽

pp. 569-576

Author(s):

I. A. Tuzankina ◽

M. A. Bolkov ◽

N. S. Zhuravleva ◽

Yu. O. Vaseneva ◽

Kh. Shinvari ◽

...

Keyword(s):

Renal Failure ◽

Hemolytic Uremic Syndrome ◽

Clinical Case ◽

Atypical Hemolytic Uremic Syndrome ◽

Clinical Manifestations ◽

Factor H ◽

Complement Factor H ◽

Chromosome 1 ◽

Complement Factor ◽

Uremic Syndrome

This article presents two clinical cases of patients with a homozygous deletion of segment of chromosome 1, which covers regions of genes associated with complement factor H, in particular CFHR3. Patients underwent in-depth clinical studies, heredity assessment, laboratory, instrumental and genetic diagnostics. The first clinical case describes a clinical case with deleted chromosome 1 segment in a 9-year-old girl who was diagnosed with atypical hemolytic-uremic syndrome. This is a complement-dependent disease that affects both adults and children. It is known that a defect in any proteins included in the alternative complement activation pathway can lead to atypical hemolytic-uremic syndrome. However, this syndrome is most often caused by defects in chromosome 1 region, including gene sequences associated with complement factor H – CFHR1 and CFHR3. Modern treatment of atypical hemolytic uremic syndrome involves targeted pathogenetic treatment, therefore, the genetic diagnosis seems to be a necessary step for differential diagnosis and confirmation. The patient had fairly typical clinical symptoms, including signs of thrombotic microangiopathy, thrombocytopenia, hemolytic anemia and increasing renal failure. It is also known that her mother had congenital hydronephrosis, and the pregnancy proceeded against a background of ureaplasma, mycoplasma, cytomegalovirus infection, chronic pyelonephritis, and preeclampsia.The second clinical case of a deleted chromosome 1 region, involving the CFHR3 gene, is a description of the disease in a boy of 8 years old, while the disease manifested with alopecia at the age of 4. Intermittent alopecia was the main symptom, while there were no signs of renal failure, thrombocytopenic purpura, and other symptoms characteristic of atypical hemolytic-uremic syndrome. The boy also revealed some congenital defects of the urinary system: bladder diverticulum, unilateral ureterohydronephrosis, and bilateral dilatation of the pyelocaliceal system. The detected genetic defect is usually associated with atypical hemolytic uremic syndrome. However, the phenotype, i.e., clinical manifestations, determined a completely different diagnosis – primary immunodeficiency, a group of complement defects, and a deficiency of complement factor H-related protein. After analyzing the given clinical cases, we can conclude that clinical manifestations may vary significantly in carriers of same gene mutations. This suggests that there are additional factors (genetic or environmental) that can influence the formation of various phenotypic manifestations of this pathology.

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COVID-19: a trigger for severe thrombotic microangiopathy in a patient with complement gene variant

Romanian Journal of Internal Medicine ◽

10.2478/rjim-2021-0040 ◽

2022 ◽

Vol 0 (0) ◽

Author(s):

Larisa Pinte ◽

Bogdan Marian Sorohan ◽

Zoltán Prohászka ◽

Mihaela Gherghiceanu ◽

Cristian Băicuş

Keyword(s):

Hemolytic Uremic Syndrome ◽

Thrombotic Microangiopathy ◽

Alternative Pathway ◽

Atypical Hemolytic Uremic Syndrome ◽

Factor H ◽

Complement C3 ◽

Uncontrolled Hypertension ◽

Complement Factor ◽

Uremic Syndrome ◽

Complement Gene

Abstract The evidence regarding thrombotic microangiopathy (TMA) related to Coronavirus Infectious Disease 2019 (COVID-19) in patients with complement gene mutations as a cause of acute kidney injury (AKI) are limited. We presented a case of a 23-year-old male patient admitted with an asymptomatic form of COVID-19, but with uncontrolled hypertension and AKI. Kidney biopsy showed severe lesions of TMA. In evolution patient had persistent microangiopathic hemolytic anemia, decreased level of haptoglobin and increased LDH level. Decreased complement C3 level and the presence of schistocytes were found for the first time after biopsy. Kidney function progressively decreased and the patient remained hemodialysis dependent. Complement work-up showed a heterozygous variant with unknown significance in complement factor I (CFI) c.-13G>A, affecting the 5' UTR region of the gene. In addition, the patient was found to be heterozygous for the complement factor H (CFH) H3 haplotype (involving the rare alleles of c.-331C>T, Q672Q and E936D polymorphisms) reported as a risk factor of atypical hemolytic uremic syndrome. This case of AKI associated with severe TMA and secondary hemolytic uremic syndrome highlights the importance of genetic risk modifiers in the alternative pathway dysregulation of the complement in the setting of COVID-19, even in asymptomatic forms.

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Infection triggered anti complement factor H (CFH) positive atypical Hemolytic Uremic Syndrome in children: lessons for the clinical nephrologist

Journal of Nephrology ◽

10.1007/s40620-020-00913-y ◽

2021 ◽

Author(s):

Rakesh Kumar Pilania ◽

Deepanjan Bhattacharya ◽

Neelam Taneja ◽

Amit Rawat ◽

Deepti Suri ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Atypical Hemolytic Uremic Syndrome ◽

Factor H ◽

Complement Factor H ◽

Complement Factor ◽

Uremic Syndrome

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Atypical Hemolytic Uremic Syndrome Associated with Complement Factor H Mutation and IgA Nephropathy: A Case Report Successfully Treated with Eculizumab

Nephron ◽

10.1159/000485194 ◽

2017 ◽

Vol 138 (4) ◽

pp. 324-327 ◽

Cited By ~ 6

Author(s):

Hironori Nakamura ◽

Mariko Anayama ◽

Mutsuki Makino ◽

Yasushi Makino ◽

Katsuhiko Tamura ◽

...

Keyword(s):

Case Report ◽

Hemolytic Uremic Syndrome ◽

Iga Nephropathy ◽

Atypical Hemolytic Uremic Syndrome ◽

Factor H ◽

Complement Factor H ◽

Complement Factor ◽

Uremic Syndrome ◽

Factor H Mutation

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Impact of compound heterozygous complement factor H mutations on development of atypical hemolytic uremic syndrome—A pedigree revisited

Molecular Immunology ◽

10.1016/j.molimm.2009.12.001 ◽

2010 ◽

Vol 47 (7-8) ◽

pp. 1585-1591 ◽

Cited By ~ 7

Author(s):

S.A. Johnson ◽

J.M. Williams ◽

S. Hakobyan ◽

A. Richards ◽

S.J. Perkins ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Atypical Hemolytic Uremic Syndrome ◽

Factor H ◽

Complement Factor H ◽

Compound Heterozygous ◽

Complement Factor ◽

Uremic Syndrome

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Case Report: Lipoprotein Glomerulopathy Complicated by Atypical Hemolytic Uremic Syndrome

Frontiers in Medicine ◽

10.3389/fmed.2021.679048 ◽

2021 ◽

Vol 8 ◽

Author(s):

Lara Kollbrunner ◽

Patricia Hirt-Minkowski ◽

Javier Sanz ◽

Elena Bresin ◽

Thomas J. Neuhaus ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Atypical Hemolytic Uremic Syndrome ◽

Factor H ◽

Complement Factor ◽

Inherited Disease ◽

Lipoprotein Glomerulopathy ◽

Gene Encoding ◽

Alternative Complement ◽

Uremic Syndrome ◽

The Complement System

Lipoprotein glomerulopathy (LPG) is a rare inherited disease caused by mutations in the APOE gene, encoding apolipoprotein E (apoE). Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by overactivation of the alternative complement pathway. Here we report the case of a 21-year-old man with LPG who developed aHUS. A functional complement assay demonstrated an overactivation of the complement system. Complementary genetic analysis revealed a homozygous aHUS risk allele for complement factor-H related 1 (CFHR1), CFHR1*B. To the best of our knowledge, this is the first report of an aHUS in a patient with LPG.

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Familial Atypical Hemolytic Uremic Syndrome with Positive pS1191L (c.3572C> T) Mutation in CFH A Single-Center Experience

10.21203/rs.2.13028/v1 ◽

2019 ◽

Author(s):

Fadime ERSOY DURSUN ◽

Gözde YESIL ◽

Hasan DURSUN ◽

Gülşah SASAK

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Family History ◽

Hemolytic Uremic Syndrome ◽

Atypical Hemolytic Uremic Syndrome ◽

Gene Mutations ◽

Factor H ◽

The Other ◽

History Of ◽

Uremic Syndrome

Abstract Background: Atypical hemolytic uremic syndrome is a condition characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, which can exhibit a poor prognosis. Gene mutations play a key role in this disease, which may be sporadic or familial. Methods: We studied, 13 people from the same family were investigated retrospectively for gene mutations of familial atypical hemolytic uremic syndrome after a patient presented to our emergency clinic with atypical hemolytic uremic syndrome and reported a family history of chronic renal failure. Results: The pS1191L mutation in the complement factor H gene was heterozygous in 6 people from the family of the patient with atypical hemolytic uremic syndrome. One of these people was our patient with acute renal failure and the other two are followed up by the Nephrology Clinic due to chronic renal failure. The other 3 persons showed no evidence of renal failure. The index case had a history of 6 sibling deaths; two of them died of chronic renal failure. Plasmapheresis and fresh frozen plasma treatment was given to our patient. When patient showed no response to this treatment, eculizumab therapy was started. Conclusions: The study demonstrated that a thorough family history should be taken in patients with atypical hemolytic uremic syndrome. These patients may have familial type of the disease and they should be screened genetically. Eculizumab should be the first choice in the treatment with plasmapheresis. It should be kept in mind that the use of eculizumab as prophylaxis in post-transplant therapy is extremely important for prevention of rejection.

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