Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Hemolytic-Uremic Syndrome

This disease belongs to thrombotic microangiopathies. It is characterized by the presence of renal insufficiency and the absence of neurological signs not attributable to uremic encephalopathy.

Historical Aspects

in 1998 an association of atypical HUS and the RCA (regulators of complement activity) gene cluster was established.[Error: Macro 'ref' doesn't exist]

Test Strategy

Ancillary to the common laboratory investigations to confirm the diagnosis of thrombotic microangiopathy the measurement of factor H plasma levels are recommended. A mutation screening is required if the level is below normal. But cases have been reported in which normal plasma levels have been found despite of documented mutations. Consequently, if there were a family history of HUS, molecular genetic investigation would be indicated anyway.

Pathogenesis

Reduced plasma levels of factor H or dysfunction of this protein may lead to HUS. But there is evidence that other genetic factors also may induce HUS. The pathogenesis of H factor related HUS is deliniated on gene test description page.

Management

In cases where a CFH or CFI mutation is found combined liver and kidney transplantation can be considered. Also plasmaphereses after transpantation can reduce the risc of tranplantation associated HUS.[Error: Macro 'ref' doesn't exist]

Registry

Alexion aHUS registry

Systematic

Thrombotic microangiopathies
Hemolytic-Uremic Syndrome
ADAMTS13
C3
C4BPA
C4BPB
CD46
CFB
CFH
CFHR1
CFHR2
CFHR3
CFHR4
CFHR5
CFI
CLU
DGKE
Methylmalonic aciduria
Methylmalonic aciduria and homocystinuria cblC
MMACHC
Methylmalonic aciduria and homocystinuria cblD
MMADHC
Methylmalonic aciduria type mut
MUT
PIGA
PLG
THBD
Poor response to Eculizumab
Thrombotic Thrombocytopenic Purpura

References:

1.

Nürnberger J et al. (2009) Eculizumab for atypical hemolytic-uremic syndrome.

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2.

Warwicker P et al. (1998) Genetic studies into inherited and sporadic hemolytic uremic syndrome.

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3.

Noris M et al. (2010) Thrombotic microangiopathy after kidney transplantation.

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4.

Zipfel PF et al. (2001) Hemolytic uremic syndrome: how do factor H mutants mediate endothelial damage?

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5.

Shao C et al. (2004) Whole exon 5 and intron 5 replaced by RHCE in DVa(Hus).

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Update: Sept. 26, 2018