(Hamburger disease, radish disease, Gasser disease, Moschowitz syndrome, HUS)

First cause of renal failure in children under 3 years of age.

Clinical presentation:

• typical form [MIM 235 400]: renal microangiopathy appearing in general 1 - 2 weeks after a bloody gastroenteritis due to verotoxins producing E coli (mostly the O157:H7 strain), more rarely in case of Streptococcus pneumoniae, Shigella or Salmonella dysenteriae gastroenteritis. It especially affects children from 1 to 10 years old. The bacterial endotoxin produces an endothelial alteration resulting in hemolytic anemia (schistocytes) and consumption of platelets resulting in occlusion of the renal arterioles. Clinical signs : pallor, lethargy, purpura, oligoanuria, hypertension, edema, sometimes convulsions caused by hypertension; sometimes: hemorrhagic colitis (32%), rectal prolapse, intussusception (3 %), heart failure (due to hypervolemia or  myocardial microangiopathy), hepatic cytolysis, pancreatitis. Symptomatic treatment: transfusions, peritoneal dialysis or hemodialysis, fresh frozen plasma, antihypertensive drugs. Renal function normalizes in 1-2 weeks in 95 % of cases. Some (4-5 %) children develop chronic renal failure.

• atypical form: more rare (approximately 5-10 % of cases). Triad of microangiopathic anemia, thrombocytopenia and renal impairment but, in general, absence of a preceding diarrheal episode. Evolution either with outbreaks of hemolysis  or to progressive renal failure.  The diuresis is often preserved with hematuria, proteinuria and arterial hypertension (50 %). Hereditary or sporadic.

Possible causes of atypical forms:

*          atypical HUS 1 (20-30 %): dysfunction of factor H [MIM 609 814, 235 400] due to a mutation in the HF1, CFHR3 or CFHR1 genes (1q31.3): loss of regulation of activation of the alternate complement pathway by factor H: recurrent infections by encapsulated bacteria such as H influenzae or S. pneumoniae; onset before 3 months of age; rapidly terminal renal failure

*         atypical HUS 2 (10-15 %): dysfunction of a CD46 membrane cofactor protein [MIM 612 922], due to a mutation of the MCP gene (1q32.2)

*  atypical HUS 3 (10 %): dysfunction of factor I [MIM 612 923], due to a mutation of the CFI gene (4q25): onset before 3 months of age; rapidly terminal renal failure

*         atypical HUS 4 (1 %): dysfunction of the factor B [MIM 612 924], due to a mutation of the CFB gene (6p21.33) 

*         atypical HUS  5: C3 dysfunction (10 %) [MIM 612 925], du to a C3 or ARMD9 gene due to a mutation (19p13.3): onset in early childhood

*         HUS atypical 6: dyfunction of thrombomodulin (5 %) [MIM 612 926], due to a mutation of the THBD gene (20p11.21): onset in early childhood

*         HUS atypical 7 [MIM 615 008]; mutation of the RONA7275 gene (17q 22), causing episodes of HUS in the first year of life and a nephrotic syndrome in the first decade; picture of membranoproliferative glomerulonephritis

*         deficiency in the metalloprotease responsible for the cleavage of the von Willebrand factor; autosomal recessive transmission of the ADAMTS gene (9q34.2)  [ MIM 274 150]: onset in early childhood

*         abnormal metabolism of vitamin B12 (cobalamin C mutations), autosomal recessive transmission: functional deficiency in methylcobalamin CoAmutase and methionine synthase due to a mutation of the MMACHC gene (1p23.2) causing methylmalonic acidemia with homocystinuria (see these topics). An early (first months of life) HUS is present in approximately 25 % of cases. Treatment: vitamin B12, folic acid and betaine. Sometimes arterial pulmonary lesions.

*         autoimmune form with autoantibodies against facteur H (10 %): treatment with corticosteroids and immunosuppressive drugs 

*         drug-induced forms

Some patients present also a problem touching the larger arteries (gangrene). Progression to chronic renal failure in the majority of cases with, in 60 % of cases, recurrence of the disease after renal transplantation. 

Treatment: in case of anomaly of the complement, infusions of plasma (+ antibiotics and gamma globulins if necessary) and early onset of treatment by eculizumab (Soliris®) (recombinant monoclonal antibody that inhibits the cleavage of C5 into C5b). Longterm treatment by eculizumab  stabilizes the disease and prevents its recurrence in the transplanted kidney. In this case, an antimeningococcal vaccination should be planned !

Anesthetic implications: 

-        typical: check hemoglobin, platelets count and renal function; check cardiac function (echocardiography) because there is a risk of fluid overload but also of ischemia by coronary artery microangiopathy; control of blood pressure (risk of cerebral hemorrhage or  thrombosis); risk of cardiac arrest at the time of the release of an abdominal compartment syndrome.

-         atypical: check hemoglobin, platelets count and renal function; avoid N2O in case of abnormal metabolism of vitamin B12; preoperative plasmapheresis and/or infusion of plasma to increase the level of factor H during surgery; if possible, avoidance of situations that may result in complement activation (infection, hypotension...)

References : 

-        Tobias JD. 
Hemolytic-uremic syndrome and myocardial dysfunction in a 9-month-old boy. 
Pediatr Anesth 2007; 17: 584-7.

-         Malina m, Gulati A, Baga A, Majid MA, Simkova E, Schaefer F. 
Peripheral gangrene in children with atypical hemolytic uremic syndrome. 
Pediatrics 2013 ; 131 : e331-5.

-        Loirat C, Mariani-Kurkdjian P, Fremeaux-Bacchi V. 
Le syndrome hémolytique-urémique en 2013. 
Arch Pédiatr 2013 ; 20 : 827-30.

-         Ben Abdallah Chabchoub R, Boukedi A, BenSalah A, Maalej B et al. 
Syndrome hémolytique et urémique atypique et déficit en ADAMTS13. 
Arch Pédiatr 2013 ; 20 : 853-7.

-         Park S-H, Kim G-S. 
Anesthetic management of living donor liver transplantation for complement factor H deficiency hemolytic uremic syndrome: a case report. 
Korean J Anesthesiol 2014; 6: 481-5. 

-        Bridier T, Lavedan P, Tafer N, Ouattara A.
Refractory cardiogenic shock complicating hemolytic uremic syndrome treated by extracorporeal life support and balloon atrial septostomy. A case report.
Pediatric Anesthesia and Critical Care J 2021; 9: 48-53

Updated: May 2022