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Atypical hemolytic-uremic syndrome with I factor anomaly(AHUS3)

MedGen UID:
414542
Concept ID:
C2752039
Finding
Synonyms: AHUS, SUSCEPTIBILITY TO, 3; Atypical hemolytic-uremic syndrome 3; HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 3
 
Gene (location): CFI (4q25)
 
Monarch Initiative: MONDO:0013041
OMIM®: 612923

Disease characteristics

Excerpted from the GeneReview: Genetic Atypical Hemolytic-Uremic Syndrome
Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. The onset of atypical HUS (aHUS) ranges from the neonatal period to adulthood. Genetic aHUS accounts for an estimated 60% of all aHUS. Individuals with genetic aHUS frequently experience relapse even after complete recovery following the presenting episode; 60% of genetic aHUS progresses to end-stage renal disease (ESRD). [from GeneReviews]
Authors:
Marina Noris  |  Elena Bresin  |  Caterina Mele, et. al.   view full author information

Additional description

From MedlinePlus Genetics
Atypical hemolytic-uremic syndrome is a disease that primarily affects kidney function. This condition, which can occur at any age, causes abnormal blood clots (thrombi) to form in small blood vessels in the kidneys. These clots can cause serious medical problems if they restrict or block blood flow. Atypical hemolytic-uremic syndrome is characterized by three major features related to abnormal clotting: hemolytic anemia, thrombocytopenia, and kidney failure.

Hemolytic anemia occurs when red blood cells break down (undergo hemolysis) prematurely. In atypical hemolytic-uremic syndrome, red blood cells can break apart as they squeeze past clots within small blood vessels. Anemia results if these cells are destroyed faster than the body can replace them. Anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate.

Thrombocytopenia is a reduced level of circulating platelets, which are cells that normally assist with blood clotting. In people with atypical hemolytic-uremic syndrome, fewer platelets are available in the bloodstream because a large number of platelets are used to make abnormal clots. Thrombocytopenia can cause easy bruising and abnormal bleeding.

Atypical hemolytic-uremic syndrome should be distinguished from a more common condition called typical hemolytic-uremic syndrome. The two disorders have different causes and different signs and symptoms. Unlike the atypical form, the typical form is caused by infection with certain strains of Escherichia coli bacteria that produce toxic substances called Shiga-like toxins. The typical form is characterized by severe diarrhea and most often affects children younger than 10. The typical form is less likely than the atypical form to involve recurrent attacks of kidney damage that lead to ESRD.

As a result of clot formation in small blood vessels, people with atypical hemolytic-uremic syndrome experience kidney damage and acute kidney failure that lead to end-stage renal disease (ESRD) in about half of all cases. These life-threatening complications prevent the kidneys from filtering fluids and waste products from the body effectively.  https://medlineplus.gov/genetics/condition/atypical-hemolytic-uremic-syndrome

Clinical features

From HPO
Anuria
MedGen UID:
358
Concept ID:
C0003460
Disease or Syndrome
Absence of urine, clinically classified as below 50ml/day.
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine).
Hemolytic-uremic syndrome
MedGen UID:
42403
Concept ID:
C0019061
Disease or Syndrome
A thrombotic microangiopathy with presence of non-immune, intravascular hemolytic anemia, thrombocytopenia and acute kidney injury. A vicious cycle of complement activation, endothelial cell damage, platelet activation, and thrombosis is the hallmark of the disease.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Acute kidney injury
MedGen UID:
388570
Concept ID:
C2609414
Injury or Poisoning
Sudden loss of renal function, as manifested by decreased urine production, and a rise in serum creatinine or blood urea nitrogen concentration (azotemia).
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Microangiopathic hemolytic anemia
MedGen UID:
65120
Concept ID:
C0221021
Disease or Syndrome
Acquired anemia due to destruction of red blood cells by physical trauma such as FIBRIN strands in the blood vessels, artificial heart valve, AORTIC COARCTATION. I can also be associated with hematologic diseases such as DISSEMINATED INTRAVASCULAR COAGULATION; HEMOLYTIC-UREMIC SYNDROME; and THROMBOTIC THROMBOCYTOPENIC PURPURA.
Decreased circulating complement C3 concentration
MedGen UID:
332469
Concept ID:
C1837512
Finding
Concentration of the complement component C3 in the blood circulation below the lower limit of normal.
Increased blood urea nitrogen
MedGen UID:
760252
Concept ID:
C0151539
Finding
An increased amount of nitrogen in the form of urea in the blood.
Elevated circulating creatinine concentration
MedGen UID:
148579
Concept ID:
C0700225
Finding
An increased amount of creatinine in the blood.

Professional guidelines

PubMed

Gastoldi S, Aiello S, Galbusera M, Breno M, Alberti M, Bresin E, Mele C, Piras R, Liguori L, Santarsiero D, Benigni A, Remuzzi G, Noris M
Front Immunol 2023;14:1112257. Epub 2023 Feb 9 doi: 10.3389/fimmu.2023.1112257. PMID: 36845135Free PMC Article
Raina R, Krishnappa V, Blaha T, Kann T, Hein W, Burke L, Bagga A
Ther Apher Dial 2019 Feb;23(1):4-21. Epub 2018 Oct 29 doi: 10.1111/1744-9987.12763. PMID: 30294946
Sawai T, Nangaku M, Ashida A, Fujimaru R, Hataya H, Hidaka Y, Kaname S, Okada H, Sato W, Yasuda T, Yoshida Y, Fujimura Y, Hattori M, Kagami S; Joint Committee of the Japanese Society of Nephrology and the Japan Pediatric Society
Clin Exp Nephrol 2014 Feb;18(1):4-9. doi: 10.1007/s10157-013-0911-8. PMID: 24343712

Recent clinical studies

Etiology

Savige J, Amos L, Ierino F, Mack HG, Symons RC, Hughes P, Nicholls K, Colville D
Ophthalmic Genet 2016 Dec;37(4):369-376. Epub 2016 Feb 25 doi: 10.3109/13816810.2015.1101777. PMID: 26915021
Loirat C, Frémeaux-Bacchi V
Orphanet J Rare Dis 2011 Sep 8;6:60. doi: 10.1186/1750-1172-6-60. PMID: 21902819Free PMC Article
Kavanagh D, Goodship TH
Curr Opin Hematol 2010 Sep;17(5):432-8. doi: 10.1097/MOH.0b013e32833cae86. PMID: 20613506
Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G
Clin J Am Soc Nephrol 2010 Oct;5(10):1844-59. Epub 2010 Jul 1 doi: 10.2215/CJN.02210310. PMID: 20595690Free PMC Article
Lämmle B, Kremer Hovinga JA, Alberio L
J Thromb Haemost 2005 Aug;3(8):1663-75. doi: 10.1111/j.1538-7836.2005.01425.x. PMID: 16102032

Diagnosis

Lemaire M, Noone D, Lapeyraque AL, Licht C, Frémeaux-Bacchi V
Clin J Am Soc Nephrol 2021 Jun;16(6):942-956. Epub 2021 Feb 3 doi: 10.2215/CJN.11830720. PMID: 33536243Free PMC Article
Yoshida Y, Kato H, Ikeda Y, Nangaku M
J Atheroscler Thromb 2019 Feb 1;26(2):99-110. Epub 2018 Nov 2 doi: 10.5551/jat.RV17026. PMID: 30393246Free PMC Article
Raina R, Krishnappa V, Blaha T, Kann T, Hein W, Burke L, Bagga A
Ther Apher Dial 2019 Feb;23(1):4-21. Epub 2018 Oct 29 doi: 10.1111/1744-9987.12763. PMID: 30294946
Loirat C, Frémeaux-Bacchi V
Orphanet J Rare Dis 2011 Sep 8;6:60. doi: 10.1186/1750-1172-6-60. PMID: 21902819Free PMC Article
Lämmle B, Kremer Hovinga JA, Alberio L
J Thromb Haemost 2005 Aug;3(8):1663-75. doi: 10.1111/j.1538-7836.2005.01425.x. PMID: 16102032

Therapy

Balwani MR, Pasari AS, Gurjar P, Bhawane A, Bawankule C, Tolani P, Kashiv P, Dubey S, Katekhaye VM
Transplant Proc 2023 Jun;55(5):1312-1315. Epub 2023 May 16 doi: 10.1016/j.transproceed.2023.02.066. PMID: 37202305
Garg N, Rennke HG, Pavlakis M, Zandi-Nejad K
Transplant Rev (Orlando) 2018 Jan;32(1):58-68. Epub 2017 Nov 4 doi: 10.1016/j.trre.2017.10.001. PMID: 29157988
Huerta A, Arjona E, Portoles J, Lopez-Sanchez P, Rabasco C, Espinosa M, Cavero T, Blasco M, Cao M, Manrique J, Cabello-Chavez V, Suñer M, Heras M, Fulladosa X, Belmar L, Sempere A, Peralta C, Castillo L, Arnau A, Praga M, Rodriguez de Cordoba S
Kidney Int 2018 Feb;93(2):450-459. Epub 2017 Sep 12 doi: 10.1016/j.kint.2017.06.022. PMID: 28911789
Verhave JC, Wetzels JF, van de Kar NC
Nephrol Dial Transplant 2014 Sep;29 Suppl 4:iv131-41. doi: 10.1093/ndt/gfu235. PMID: 25165180
Kavanagh D, Goodship TH
Curr Opin Hematol 2010 Sep;17(5):432-8. doi: 10.1097/MOH.0b013e32833cae86. PMID: 20613506

Prognosis

Piras R, Valoti E, Alberti M, Bresin E, Mele C, Breno M, Liguori L, Donadelli R, Rigoldi M, Benigni A, Remuzzi G, Noris M
Front Immunol 2022;13:1011580. Epub 2023 Jan 30 doi: 10.3389/fimmu.2022.1011580. PMID: 36793547Free PMC Article
Yoshida Y, Kato H, Ikeda Y, Nangaku M
J Atheroscler Thromb 2019 Feb 1;26(2):99-110. Epub 2018 Nov 2 doi: 10.5551/jat.RV17026. PMID: 30393246Free PMC Article
Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey MA, Ngo S, Moulin B, Servais A, Provot F, Rostaing L, Burtey S, Niaudet P, Deschênes G, Lebranchu Y, Zuber J, Loirat C
Clin J Am Soc Nephrol 2013 Apr;8(4):554-62. Epub 2013 Jan 10 doi: 10.2215/CJN.04760512. PMID: 23307876Free PMC Article
Loirat C, Frémeaux-Bacchi V
Orphanet J Rare Dis 2011 Sep 8;6:60. doi: 10.1186/1750-1172-6-60. PMID: 21902819Free PMC Article
Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G
Clin J Am Soc Nephrol 2010 Oct;5(10):1844-59. Epub 2010 Jul 1 doi: 10.2215/CJN.02210310. PMID: 20595690Free PMC Article

Clinical prediction guides

Khandelwal P, Krishnasamy S, Govindarajan S, Kumar M, Marik B, Sinha A, Hari P, Bagga A
Pediatr Nephrol 2022 Sep;37(9):2151-2156. Epub 2022 Jan 28 doi: 10.1007/s00467-021-05390-4. PMID: 35089377Free PMC Article
Menne J, Delmas Y, Fakhouri F, Licht C, Lommelé Å, Minetti EE, Provôt F, Rondeau E, Sheerin NS, Wang J, Weekers LE, Greenbaum LA
BMC Nephrol 2019 Apr 10;20(1):125. doi: 10.1186/s12882-019-1314-1. PMID: 30971227Free PMC Article
Yoshida Y, Kato H, Ikeda Y, Nangaku M
J Atheroscler Thromb 2019 Feb 1;26(2):99-110. Epub 2018 Nov 2 doi: 10.5551/jat.RV17026. PMID: 30393246Free PMC Article
Quiroga B, de Lorenzo A, Vega C, de Alvaro F
Am J Case Rep 2016 Dec 15;17:950-956. doi: 10.12659/ajcr.899764. PMID: 27974740Free PMC Article
Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G
Clin J Am Soc Nephrol 2010 Oct;5(10):1844-59. Epub 2010 Jul 1 doi: 10.2215/CJN.02210310. PMID: 20595690Free PMC Article

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