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. Eculizumab, a potent C5 inhibitor, is frequently used in therapy. A CFB inhibitor, iptacopan, is currently clinically tested.[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.

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

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

4.	Kavanagh D et al. (2023) Design and Rationale of the APPELHUS Phase 3 Open-Label Study of Factor B Inhibitor Iptacopan for Atypical Hemolytic Uremic Syndrome.

5.	None (2001) Hemolytic uremic syndrome: how do factor H mutants mediate endothelial damage?

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

7.	OMIM.ORG article Omim 235400

8.	Orphanet article Orphanet ID 2134

9.	Wikipedia article Wikipedia EN (Hemolytic-uremic_syndrome)