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IgA nephropathy associated with a novel N-terminal mutation in factor H

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Abstract

Most patients with IgA nephropathy exhibit complement deposition in the glomerular mesangium. Certain cases of IgA nephropathy have been associated with reduced levels of complement factor H. A recent study could not demonstrate mutations at the C-terminal of factor H. We describe a novel heterozygous mutation in factor H, position A48S (nucleotide position 142 G > T, alanine > serine), detected in exon 2 of a 14-year-old girl with IgA nephropathy. The patient exhibited reduced levels of C3 and factor H, the latter suggesting that the mutation affected factor H secretion. The patient developed initial signs and symptoms of glomerulonephritis at the age of 9 years but presented again at the age of 14 years with weight gain, renal failure, nephrotic-range proteinuria and malignant hypertension. Blood tests suggested the development of microangiopathic hemolytic anemia (MAHA) but the renal biopsy was mostly indicative of chronic changes associated with IgA nephropathy as well as vascular changes associated with malignant hypertension. Immunofluorescence exhibited deposits of IgA, C3, and IgM. Screening of the factor H gene revealed, in addition to the mutation, three heterozygous hemolytic uremic syndrome -associated risk polymorphisms (−257 c/t, 2089 a/g, and 2881 g/t) which may have increased the patient’s susceptibility to the occurrence of MAHA triggered by malignant hypertension. The combined clinical picture of IgA nephropathy and MAHA may have been partly related to the alterations in factor H.

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Acknowledgements

This study was supported by grants from The Swedish Research Council (K2010-65X-14008-10-3), The Torsten and Ragnar Söderberg Foundation, The fund for Renal Research, Crown Princess Lovisa’s Society for Child Care, Konung Gustaf V:s 80-årsfond, Fanny Ekdahl’s Foundation (all to DK), funding from Region Skåne (to RS and DK); grants from Kristianstad Högskola and the Samariten Foundation (to RS). Diana Karpman is the recipient of a clinical-experimental research fellowship from the Royal Swedish Academy of Sciences.

Conflicts of interest

The authors declare that they do not have any conflicts of interest and no financial relationships that might have influenced the present work.

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  1. Magnus Söderberg

    Present address: AstraZeneca R&D, Södertälje, Sweden

Authors and Affiliations

  1. Department of Pediatrics, Clinical Sciences Lund, Lund University, 22185, Lund, Sweden

    Roland Schmitt, AnnCharlotte Kristoffersson & Diana Karpman

  2. Division of Pediatrics, Department for Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden

    Rafael T. Krmar

  3. Department of Pathology, Karolinska University Hospital, Huddinge, Sweden

    Magnus Söderberg

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  1. Roland Schmitt
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  2. Rafael T. Krmar
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  3. AnnCharlotte Kristoffersson
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  4. Magnus Söderberg
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  5. Diana Karpman
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Correspondence to Diana Karpman.

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Schmitt, R., Krmar, R.T., Kristoffersson, A. et al. IgA nephropathy associated with a novel N-terminal mutation in factor H. Eur J Pediatr 170, 107–110 (2011). https://doi.org/10.1007/s00431-010-1279-3

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  • DOI: https://doi.org/10.1007/s00431-010-1279-3

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