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Atypical hemolytic-uremic syndrome with B factor anomaly(AHUS4)

MedGen UID:
416691
Concept ID:
C2752038
Finding
Synonyms: AHUS, SUSCEPTIBILITY TO, 4; Atypical hemolytic-uremic syndrome 4; HEMOLYTIC UREMIC SYNDROME, ATYPICAL, SUSCEPTIBILITY TO, 4
 
Gene (location): CFB (6p21.33)
 
Monarch Initiative: MONDO:0013042
OMIM®: 612924

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 descriptions

From OMIM
Atypical hemolytic uremic syndrome-4 (AHUS4) is characterized by thrombocytopenia, Coomb test-negative microangiopathic hemolytic anemia, and acute renal failure, in the absence of E. coli infection (summary by Goicoechea de Jorge et al., 2007). For a general phenotypic description and a discussion of genetic heterogeneity of aHUS, see AHUS1 (235400).  http://www.omim.org/entry/612924
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.

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.

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.

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.  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.
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.

Recent clinical studies

Etiology

Sánchez-Moreno A, de la Cerda F, Rodríguez-Barba A, Fijo J, Bedoya R, Arjona E, de Córdoba SR
Pediatr Transplant 2021 May;25(3):e13903. Epub 2020 Nov 20 doi: 10.1111/petr.13903. PMID: 33217135
Phillips EH, Westwood JP, Brocklebank V, Wong EK, Tellez JO, Marchbank KJ, McGuckin S, Gale DP, Connolly J, Goodship TH, Kavanagh D, Scully MA
J Thromb Haemost 2016 Jan;14(1):175-85. Epub 2016 Jan 11 doi: 10.1111/jth.13189. PMID: 26559391Free PMC Article
Bresin E, Rurali E, Caprioli J, Sanchez-Corral P, Fremeaux-Bacchi V, Rodriguez de Cordoba S, Pinto S, Goodship TH, Alberti M, Ribes D, Valoti E, Remuzzi G, Noris M; European Working Party on Complement Genetics in Renal Diseases
J Am Soc Nephrol 2013 Feb;24(3):475-86. Epub 2013 Feb 21 doi: 10.1681/ASN.2012090884. PMID: 23431077Free PMC Article
Le Quintrec M, Zuber J, Moulin B, Kamar N, Jablonski M, Lionet A, Chatelet V, Mousson C, Mourad G, Bridoux F, Cassuto E, Loirat C, Rondeau E, Delahousse M, Frémeaux-Bacchi V
Am J Transplant 2013 Mar;13(3):663-75. Epub 2013 Jan 28 doi: 10.1111/ajt.12077. PMID: 23356914
Westra D, Volokhina E, van der Heijden E, Vos A, Huigen M, Jansen J, van Kaauwen E, van der Velden T, van de Kar N, van den Heuvel L
Nephrol Dial Transplant 2010 Jul;25(7):2195-202. Epub 2010 Jan 26 doi: 10.1093/ndt/gfq010. PMID: 20106822

Diagnosis

Wu H, Su S, Li L, Zhang L
Medicine (Baltimore) 2021 Mar 19;100(11):e25069. doi: 10.1097/MD.0000000000025069. PMID: 33725982Free PMC Article
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
Phillips EH, Westwood JP, Brocklebank V, Wong EK, Tellez JO, Marchbank KJ, McGuckin S, Gale DP, Connolly J, Goodship TH, Kavanagh D, Scully MA
J Thromb Haemost 2016 Jan;14(1):175-85. Epub 2016 Jan 11 doi: 10.1111/jth.13189. PMID: 26559391Free PMC Article
Polito MG, Kirsztajn GM
J Bras Nefrol 2010 Jul-Sep;32(3):303-15. PMID: 21103695

Prognosis

Phillips EH, Westwood JP, Brocklebank V, Wong EK, Tellez JO, Marchbank KJ, McGuckin S, Gale DP, Connolly J, Goodship TH, Kavanagh D, Scully MA
J Thromb Haemost 2016 Jan;14(1):175-85. Epub 2016 Jan 11 doi: 10.1111/jth.13189. PMID: 26559391Free PMC Article
Bresin E, Rurali E, Caprioli J, Sanchez-Corral P, Fremeaux-Bacchi V, Rodriguez de Cordoba S, Pinto S, Goodship TH, Alberti M, Ribes D, Valoti E, Remuzzi G, Noris M; European Working Party on Complement Genetics in Renal Diseases
J Am Soc Nephrol 2013 Feb;24(3):475-86. Epub 2013 Feb 21 doi: 10.1681/ASN.2012090884. PMID: 23431077Free PMC Article
Le Quintrec M, Zuber J, Moulin B, Kamar N, Jablonski M, Lionet A, Chatelet V, Mousson C, Mourad G, Bridoux F, Cassuto E, Loirat C, Rondeau E, Delahousse M, Frémeaux-Bacchi V
Am J Transplant 2013 Mar;13(3):663-75. Epub 2013 Jan 28 doi: 10.1111/ajt.12077. PMID: 23356914
Westra D, Volokhina E, van der Heijden E, Vos A, Huigen M, Jansen J, van Kaauwen E, van der Velden T, van de Kar N, van den Heuvel L
Nephrol Dial Transplant 2010 Jul;25(7):2195-202. Epub 2010 Jan 26 doi: 10.1093/ndt/gfq010. PMID: 20106822

Clinical prediction guides

Phillips EH, Westwood JP, Brocklebank V, Wong EK, Tellez JO, Marchbank KJ, McGuckin S, Gale DP, Connolly J, Goodship TH, Kavanagh D, Scully MA
J Thromb Haemost 2016 Jan;14(1):175-85. Epub 2016 Jan 11 doi: 10.1111/jth.13189. PMID: 26559391Free PMC Article
Bresin E, Rurali E, Caprioli J, Sanchez-Corral P, Fremeaux-Bacchi V, Rodriguez de Cordoba S, Pinto S, Goodship TH, Alberti M, Ribes D, Valoti E, Remuzzi G, Noris M; European Working Party on Complement Genetics in Renal Diseases
J Am Soc Nephrol 2013 Feb;24(3):475-86. Epub 2013 Feb 21 doi: 10.1681/ASN.2012090884. PMID: 23431077Free PMC Article
Le Quintrec M, Zuber J, Moulin B, Kamar N, Jablonski M, Lionet A, Chatelet V, Mousson C, Mourad G, Bridoux F, Cassuto E, Loirat C, Rondeau E, Delahousse M, Frémeaux-Bacchi V
Am J Transplant 2013 Mar;13(3):663-75. Epub 2013 Jan 28 doi: 10.1111/ajt.12077. PMID: 23356914
Westra D, Volokhina E, van der Heijden E, Vos A, Huigen M, Jansen J, van Kaauwen E, van der Velden T, van de Kar N, van den Heuvel L
Nephrol Dial Transplant 2010 Jul;25(7):2195-202. Epub 2010 Jan 26 doi: 10.1093/ndt/gfq010. PMID: 20106822

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