Recurrent haemolytic uraemic syndrome and acquired hypomorphic variant of the third component of complement

Roodhooft, A. M.; McLean, Robert H.; Elst, Evelyne M.; Acker, K. J. Van

doi:10.1007/bf00858631

Cited by 40 publications

(24 citation statements)

References 8 publications

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“…Decreased C3 levels also occur in the acute stage of typical HUS [10,11,36]. Atypical HUS associated with persistent hypocomplementemia has been reported previously [8,9,[37][38][39]. In the type of hereditary atypical HUS presented here, low C3 levels were found in the 9 patients that could be examined.…”

Section: Discussionmentioning

confidence: 57%

Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H

Ohali

Shalev

Schlesinger

et al. 1998

Pediatric Nephrology

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We describe the clinical course, complement components, and pathological findings of 10 infants with autosomal recessive hemolytic uremic syndrome (HUS). All patients were members of one extended highly inbred Bedouin kindred. The median age of presentation was 2 weeks (range 1-20 weeks). Eight patients died, 2 patients are alive, on dialysis. Renal biopsies revealed thrombotic microangiopathy with a predominant early arteriolar involvement and subsequent development of ischemic glomerular changes. Immunofluorescence was positive for C3 in glomeruli. All patients had low complement components levels during and between relapses, and in some this was evident soon after birth and prior to the onset of symptoms. This deficiency could not be normalized by repeated plasma transfusions. Biosynthetic labelling of patients' fibroblasts demonstrated normal rates of C3 protein synthesis. Serum factor H levels were greatly decreased or absent in 4 patients tested and moderately decreased in 15 of 23 healthy unaffected siblings and patients. This defect may cause complement activation and consumption, possibly at the endothelial cell level.

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Section: Discussionmentioning

confidence: 57%

Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H

Ohali

Shalev

Schlesinger

et al. 1998

Pediatric Nephrology

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“…This is not unexpected as IF, like CFH, is predominantly synthesized by the liver and thus a renal allograft will not correct the underlying defect. From individuals reported in the literature and unpublished from our own cohort, the recurrence rate in those with CFH mutations and/or CFH deficiency is approximately 80% (2,4,6,7,(25)(26)(27)(28)(29)(30).…”

Section: Discussionmentioning

confidence: 97%

Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome

Kavanagh¹,

Kemp²,

Mayland³

et al. 2005

Journal of the American Society of Nephrology

312

168

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Mutations in the plasma complement regulator factor H (CFH) and the transmembrane complement regulator membrane co-factor protein (MCP) have been shown to predispose to atypical hemolytic uremic syndrome (HUS). Both of these proteins act as co-factors for complement factor I (IF). IF is a highly specific serine protease that cleaves the ␣-chains of C3b and C4b and thus downregulates activation of both the classical and the alternative complement pathways. This study looked for IF mutations in a panel of 76 patients with HUS. Mutations were detected in two patients, both of whom had reduced serum IF levels. A heterozygous bp change, c.463 G>A, which results in a premature stop codon (W127X), was found in one, and in the other, a heterozygous single base pair deletion in exon 7 (del 922C) was detected. Both patients had a history of recurrent HUS after transplantation. This is in accordance with the high rate of recurrence in patients with CFH mutations. Patients who are reported to have mutations in MCP, by contrast, do not have recurrence after transplantation. As with CFH-and MCPassociated HUS, there was incomplete penetrance in the family of one of the affected individuals. This study provides further evidence that atypical HUS is a disease of complement dysregulation.

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“…Of the 11 patients, 5 lost their graft because of HUS recurrence (sporadic case in [8]-patient F34 and F39 and sporadic case in [36], previously published in [37], case 1 in [40]). Another patient lost his graft on day 27 from either vascular rejection or recurrence of HUS [38]. The 5 other patients had no recurrence of HUS after transplantation, although 2 lost their graft from early vascular rejection with some thrombotic microangiopathy lesions in 1 (P. Niaudet, unpublished data), without thrombotic microangiopathy lesions in the other [39].…”

Section: The Risk Of Hus Recurrence In Patients With Hus Associated Wmentioning

confidence: 92%

“…Eleven patients (7 in the literature [8,36,37,38,39,40], 3 in Hôpital des Enfants-Malades, P. Niaudet, unpublished data, 1 in Hôpital Robert Debré, C. Loirat, unpublished data) with HUS associated with factor H deficiency have a documented post-transplant course (Tables 3 and 4). HUS started during infancy or childhood in 8, during adulthood in 3.…”

Section: The Risk Of Hus Recurrence In Patients With Hus Associated Wmentioning

confidence: 94%

The risk of recurrence of hemolytic uremic syndrome after renal transplantation in children

Loirat

Niaudet

2003

Pediatric Nephrology

136

105

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We reviewed the literature to analyze the risk of recurrence of hemolytic uremic syndrome (HUS) after renal transplantation in children. Among 118 children transplanted after post-diarrheal (D+) HUS, 1 (0.8%) had recurrence with graft loss. Among 63 children transplanted after HUS not associated with a prodrome of diarrhea (D-) of unknown mechanism, 13 (21%) had recurrence with graft loss. Of 11 patients with HUS associated with factor H deficiency who were transplanted, 5 lost the graft because of recurrence. Of 7 patients with HUS associated with normal factor H concentration but mutations in factor H gene who were transplanted, probably 2 had recurrence. Three patients with HUS associated with low serum C3, but no factor H deficiency or mutation lost their graft because of recurrence. The risk of recurrence in the autosomal recessive forms of HUS of unknown mechanism is not documented in children, but is around 60% in adults. A similar risk has been reported in the autosomal dominant forms. The only transplant patient with a constitutional deficiency of von Willebrand factor-cleaving protease had recurrence. Further efforts to document the post-transplant course of patients with D- HUS and progress in the understanding of the mechanisms and genetics of the disease are needed to allow more accurate prediction of the recurrence risk and to define therapeutic approaches.

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Recurrent haemolytic uraemic syndrome and acquired hypomorphic variant of the third component of complement

Cited by 40 publications

References 8 publications

Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H

Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H

Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome

The risk of recurrence of hemolytic uremic syndrome after renal transplantation in children

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