Format

Send to:

Choose Destination

Hemolytic uremic syndrome, atypical, susceptibility to, 1(AHUS1)

MedGen UID:
412743
Concept ID:
C2749604
Finding
Synonyms: AHUS, SUSCEPTIBILITY TO, 1; Atypical hemolytic-uremic syndrome 1
 
Genes (locations): CFH (1q31.3); CFHR1 (1q31.3); CFHR3 (1q31.3)
 
Monarch Initiative: MONDO:0009335
OMIM®: 235400

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
Typical hemolytic uremic syndrome is characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia associated with distorted erythrocytes ('burr cells'). The vast majority of cases (90%) are sporadic, occur in children under 3 years of age, and are associated with epidemics of diarrhea caused by verotoxin-producing E. coli. The death rate is very low, about 30% of cases have renal sequelae, and there is usually no relapse of the disease. This form of HUS usually presents with a diarrhea prodrome (thus referred to as D+HUS) and has a good prognosis in most cases. In contrast, a subgroup of patients with HUS have an atypical presentation (aHUS or D-HUS) without a prodrome of enterocolitis and diarrhea and have a much poorer prognosis, with a tendency to relapse and frequent development of end-stage renal failure or death. These cases tend to be familial. Both autosomal recessive and autosomal dominant inheritance have been reported (Goodship et al., 1997; Taylor, 2001; Veyradier et al., 2003; Noris et al., 2003). Noris and Remuzzi (2009) provided a detailed review of atypical HUS. Genetic Heterogeneity of Atypical Hemolytic Uremic Syndrome Atypical HUS is a genetically heterogeneous condition. Susceptibility to the development of the disorder can be conferred by mutations in various components of or regulatory factors in the complement cascade system (Jozsi et al., 2008). See AHUS2 (612922), AHUS3 (612923), AHUS4 (612924), AHUS5 (612925), and AHUS6 (612926). AHUS7 (see 615008) is caused by mutation in the DGKE gene (601440), which is not part of the complement cascade system. AHUS8 (301110) is caused by mutation in the C1GALT1C1 gene (300611), encoding a molecular chaperone with an essential role in mucin-type O-glycan biosynthesis, on chromosome Xq23.  http://www.omim.org/entry/235400
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.
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.
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.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Aphasia
MedGen UID:
8159
Concept ID:
C0003537
Mental or Behavioral Dysfunction
An acquired language impairment of some or all of the abilities to produce or comprehend speech and to read or write.
Coma
MedGen UID:
1054
Concept ID:
C0009421
Disease or Syndrome
The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli.
Hemiparesis
MedGen UID:
6783
Concept ID:
C0018989
Finding
Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a complete loss of strength, whereas hemiparesis refers to an incomplete loss of strength.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Cognitive impairment
MedGen UID:
90932
Concept ID:
C0338656
Mental or Behavioral Dysfunction
Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Reticulocytosis
MedGen UID:
60089
Concept ID:
C0206160
Finding
An elevation in the number of reticulocytes (immature erythrocytes) in the peripheral blood circulation.
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.
Schistocytosis
MedGen UID:
576247
Concept ID:
C0344386
Laboratory or Test Result
The presence of an abnormal number of fragmented red blood cells (schistocytes) in the blood.
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.
Decreased circulating complement factor H concentration
MedGen UID:
409784
Concept ID:
C1969222
Finding
Concentration of the complement component factor H in the blood circulation below the lower limit of normal.
Decreased circulating complement factor I concentration
MedGen UID:
370868
Concept ID:
C1970257
Finding
Concentration of the complement component factor I in the blood circulation below the lower limit of normal.
Decreased circulating complement factor B concentration
MedGen UID:
867275
Concept ID:
C4021636
Finding
Concentration of the complement component factor B in the blood circulation below the lower limit of normal.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Hyperlipidemia
MedGen UID:
5692
Concept ID:
C0020473
Disease or Syndrome
An elevated lipid concentration in the blood.
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.
Purpura
MedGen UID:
19584
Concept ID:
C0034150
Disease or Syndrome
Purpura (from Latin

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
Nagarajah S, Tepel M, Nielsen C, Assing K, Palarasah Y, Andersen LLT, Lange LB, Bistrup C
BMC Nephrol 2019 Aug 7;20(1):307. doi: 10.1186/s12882-019-1469-9. PMID: 31390992Free PMC Article

Recent clinical studies

Etiology

Moscvin M, Liacos CI, Chen T, Theodorakakou F, Fotiou D, Hossain S, Rowell S, Leblebjian H, Regan E, Czarnecki P, Bagnoli F, Bolli N, Richardson P, Rennke HG, Dimopoulos MA, Kastritis E, Bianchi G
Blood Cancer J 2023 Feb 27;13(1):31. doi: 10.1038/s41408-023-00802-0. PMID: 36849497Free PMC Article
Lingwood C
Front Cell Infect Microbiol 2020;10:123. Epub 2020 Mar 31 doi: 10.3389/fcimb.2020.00123. PMID: 32296648Free PMC Article
Bowen EE, Coward RJ
Am J Physiol Renal Physiol 2018 Mar 1;314(3):F454-F461. Epub 2017 Nov 22 doi: 10.1152/ajprenal.00376.2017. PMID: 29167171Free PMC Article
Bruel A, Kavanagh D, Noris M, Delmas Y, Wong EKS, Bresin E, Provôt F, Brocklebank V, Mele C, Remuzzi G, Loirat C, Frémeaux-Bacchi V, Fakhouri F
Clin J Am Soc Nephrol 2017 Aug 7;12(8):1237-1247. Epub 2017 Jun 8 doi: 10.2215/CJN.00280117. PMID: 28596415Free PMC Article
Zuber J, Le Quintrec M, Sberro-Soussan R, Loirat C, Frémeaux-Bacchi V, Legendre C
Nat Rev Nephrol 2011 Jan;7(1):23-35. Epub 2010 Nov 23 doi: 10.1038/nrneph.2010.155. PMID: 21102542

Diagnosis

Abu Jawdeh BG, Khan MA
Clin Nephrol 2023 Aug;100(2):75-81. doi: 10.5414/CN111160. PMID: 37288831
Moscvin M, Liacos CI, Chen T, Theodorakakou F, Fotiou D, Hossain S, Rowell S, Leblebjian H, Regan E, Czarnecki P, Bagnoli F, Bolli N, Richardson P, Rennke HG, Dimopoulos MA, Kastritis E, Bianchi G
Blood Cancer J 2023 Feb 27;13(1):31. doi: 10.1038/s41408-023-00802-0. PMID: 36849497Free PMC Article
Xu B, Kang Y, Du Y, Guo W, Zhu L, Zhang H
Front Immunol 2022;13:755694. Epub 2022 Jan 21 doi: 10.3389/fimmu.2022.755694. PMID: 35126388Free PMC Article
Wong EKS, Kavanagh D
Semin Immunopathol 2018 Jan;40(1):49-64. Epub 2018 Jan 11 doi: 10.1007/s00281-017-0663-8. PMID: 29327071Free PMC Article
Kavanagh D, Goodship T
Nephron Clin Pract 2011;118(1):c37-42. Epub 2010 Nov 11 doi: 10.1159/000320901. PMID: 21071971

Therapy

Abu Jawdeh BG, Khan MA
Clin Nephrol 2023 Aug;100(2):75-81. doi: 10.5414/CN111160. PMID: 37288831
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
Merrill SA, Brodsky RA
Hematology Am Soc Hematol Educ Program 2018 Nov 30;2018(1):371-376. doi: 10.1182/asheducation-2018.1.371. PMID: 30504334Free PMC Article
Bruel A, Kavanagh D, Noris M, Delmas Y, Wong EKS, Bresin E, Provôt F, Brocklebank V, Mele C, Remuzzi G, Loirat C, Frémeaux-Bacchi V, Fakhouri F
Clin J Am Soc Nephrol 2017 Aug 7;12(8):1237-1247. Epub 2017 Jun 8 doi: 10.2215/CJN.00280117. PMID: 28596415Free PMC Article
Zuber J, Le Quintrec M, Sberro-Soussan R, Loirat C, Frémeaux-Bacchi V, Legendre C
Nat Rev Nephrol 2011 Jan;7(1):23-35. Epub 2010 Nov 23 doi: 10.1038/nrneph.2010.155. PMID: 21102542

Prognosis

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
Wu D, Chen J, Ling C, Chen Z, Fan J, Sun Q, Meng Q, Liu X
Nephron 2021;145(4):415-427. Epub 2021 Apr 19 doi: 10.1159/000513009. PMID: 33873197
Bowen EE, Coward RJ
Am J Physiol Renal Physiol 2018 Mar 1;314(3):F454-F461. Epub 2017 Nov 22 doi: 10.1152/ajprenal.00376.2017. PMID: 29167171Free 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
Kavanagh D, Goodship T
Nephron Clin Pract 2011;118(1):c37-42. Epub 2010 Nov 11 doi: 10.1159/000320901. PMID: 21071971

Clinical prediction guides

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
May O, Merle NS, Grunenwald A, Gnemmi V, Leon J, Payet C, Robe-Rybkine T, Paule R, Delguste F, Satchell SC, Mathieson PW, Hazzan M, Boulanger E, Dimitrov JD, Fremeaux-Bacchi V, Frimat M, Roumenina LT
Front Immunol 2018;9:3008. Epub 2018 Dec 20 doi: 10.3389/fimmu.2018.03008. PMID: 30619356Free PMC Article
Gavriilaki E, Yuan X, Ye Z, Ambinder AJ, Shanbhag SP, Streiff MB, Kickler TS, Moliterno AR, Sperati CJ, Brodsky RA
Blood 2015 Jun 4;125(23):3637-46. Epub 2015 Apr 10 doi: 10.1182/blood-2015-02-629683. PMID: 25862562Free PMC Article
Kavanagh D, Goodship T
Nephron Clin Pract 2011;118(1):c37-42. Epub 2010 Nov 11 doi: 10.1159/000320901. PMID: 21071971
Sullivan M, Erlic Z, Hoffmann MM, Arbeiter K, Patzer L, Budde K, Hoppe B, Zeier M, Lhotta K, Rybicki LA, Bock A, Berisha G, Neumann HP
Ann Hum Genet 2010 Jan;74(1):17-26. doi: 10.1111/j.1469-1809.2009.00554.x. PMID: 20059470

Recent systematic reviews

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...