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01-07-2013 | Brief Report

Atypical glomerulopathy associated with the cblE inborn error of vitamin B₁₂ metabolism

Authors: Erin A. Paul, Marta Guttenberg, Paige Kaplan, David Watkins, David S. Rosenblatt, James R. Treat, Bernard S. Kaplan

Published in: Pediatric Nephrology | Issue 7/2013

Abstract

Background

The cblE disorder is an inherited disorder of vitamin B₁₂ metabolism that results in elevated levels of homocysteine and decreased methionine in body fluids. Renal complications have been reported in patients with cblC disease, but not in those with cblE disease. The renal complications of cblC disease include thrombotic microangiopathy (TMA), neonatal hemolytic uremic syndrome, chronic renal failure, tubulointerstitial nephritis and proximal renal tubular acidosis. Previously, we reported a patient with cblC disease who had an atypical glomerulopathy that manifested with proteinuria and progressive renal insufficiency.

Case-Diagnosis/Treatment

Studies were done on cultured fibroblasts. Renal biopsy tissue was examined by light and electron microscopy. There was decreased incorporation of labeled methyltetrahydrofolate and decreased synthesis of methylcobalamin. Complementation analysis placed the patient into the cblE complementation group. The findings from the histological and ultrastructural studies of renal biopsy were similar, but not identical, to those of idiopathic membranoproliferative glomerulonephritis (MPGN) and overlapped with those of TMA.

Conclusions

We describe a patient with cblE disease who had an atypical glomerulopathy similar to MPGN. Additional findings included migraine headaches, hypothyroidism and livedo reticularis.

Carmel R, Green R, Rosenblatt DS, Watkins D (2003) Update on cobalamin, folate, and homocysteine. Hematol Am Soc Hematol Educ Program 62–81

Watkins D, Rosenblatt DS (2012) Update and new concepts in vitamin responsive disorders of folate transport and metabolism. J Inherit Metab Dis 35:665–670PubMedCrossRef

Watkins D, Rosenblatt DS (2011) Inherited disorders of folate and cobalamin transport and metabolism. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A (eds) The online metabolic and molecular bases of inherited disease. McGraw-Hill, New York. Chapter 155, pp 1–6. doi:10.1036/ommbid.187

Coelho D, Kim JC, Miousse IR, Fung S, Du Moulin M, Buers I, Suormala T, Burda P, Frapolli M, Stucki M, Nürnberg P, Thiele H, Robenek H, Höhne W, Longo N, Pasquali M, Mengel E, Watkins D, Shoubridge EA, Majewski J, Rosenblatt DS, Fowler B, Rutsch F, Baumgartner M (2012) Mutations in ABCD4 cause a new inborn error of vitamin B₁₂ metabolism. Nature Genet 44:1152–1155PubMedCrossRef

Vilaseca MA, Vilarinho L, Zavadakova P, Vela E, Cleto E, Pineda M, Coimbra E, Suormala T, Fowler B, Kozich V (2003) CblE type of homocystinuria: mild clinical phenotype in two probands homozygous for a novel mutation in the MTRR gene. J Inherit Metab Dis 26:361–369PubMedCrossRef

Steen C, Rosenblatt DS, Scheying H, Braeuer HC, Kohlschutter A (1997) Cobalamin E (cblE) disease: a severe neurological disorder with megaloblastic anaemia, homocystinuria and low serum methionine. J Inherit Metab Dis 20:705–706PubMedCrossRef

Yamada K, Gravel RA, Toraya T, Matthews RG (2006) Human methionine synthase reductase is a molecular chaperone for human methionine synthase. Proc Natl Acad Sci USA 103:9476–9481PubMedCrossRef

Wahlstedt-Fröberg V, Pettersson T, Aminoff M, Dugué B, Gräsbeck R (2003) Proteinuria in cubilin-deficient patients with selective vitamin B₁₂ malabsorption. Pediatr Nephrol 18:417–421PubMed

Russo P, Doyon J, Sonsino E, Ogier H, Saudubray JM (1992) A congenital anomaly of vitamin B12 metabolism: a study of three cases. Hum Pathol 23:504–512PubMedCrossRef

10.

Sharma AP, Greenberg CR, Prasad AN, Prasad C (2007) Hemolytic uremic syndrome (HUS) secondary to cobalamin C (cblC) disorder. Pediatr Nephrol 22:2097–2103PubMedCrossRef

11.

Van Hove JL, Van Damme-Lombaerts R, Grünewald S, Peters H, Van Damme B, Fryns JP, Arnout J, Wevers R, Baumgartner ER, Fowler B (2002) Cobalamin disorder Cbl-C presenting with late-onset thrombotic microangiopathy. Am J Med Genet 111:195–201PubMedCrossRef

12.

Guigonis V, Frémeaux-Bacchi V, Giraudier S, Favier R, Borderie D, Massy Z, Mougenot B, Rosenblatt DS, Deschênes G (2005) Late-onset thrombocytic microangiopathy caused by cblC disease: association with a factor H mutation. Am J Kidney Dis 45:588–595PubMedCrossRef

13.

Hörster F, Baumgartner MR, Viardot C, Suormala T, Burgard P, Fowler B, Hoffmann GF, Garbade SF, Kölker S, Baumgartner ER (2007) Long-term outcome in methylmalonic acidurias is influenced by the underlying defect (mut⁰, mut^-, cblA, cblB). Pediatr Res 62:225–230PubMedCrossRef

14.

Cosson MA, Benoist JF, Touati G, Déchaux M, Royer N, Grandin L, Jais JP, Boddaert N, Barbier V, Desguerre I, Campeau PM, Rabier D, Valayannopoulos V, Niaudet P, de Lonlay P (2009) Long-term outcome in methylmalonic aciduria: a series of 30 French patients. Mol Genet Metab 97:172–178PubMedCrossRef

15.

Brandstetter Y, Weinhouse E, Splaingard ML, Tang TT (1990) Cor pulmonale as a complication of methylmalonic acidemia and homocystinuria (Cb1-C type). Am J Med Genet 36:167–171PubMedCrossRef

16.

Brunelli SM, Meyers KE, Guttenberg M, Kaplan P, Kaplan BS (2002) Cobalamin C deficiency complicated by an atypical glomerulopathy. Pediatr Nephrol 17:800–803PubMedCrossRef

17.

Meyers KE, Strife CF, Witzleben C, Kaplan BS (1996) Discordant renal histopathologic findings and complement profiles in membranoproliferative glomerulonephritis type III. Am J Kidney Dis 28(6):804–810PubMedCrossRef

18.

Alchi B, Jayne D (2010) Membranoproliferative glomerulonephritis. Pediatr Nephrol 25:1409–1418PubMedCrossRef

19.

Bomback AS, Appel GB (2012) Pathogenesis of the C3 glomerulopathies and reclassification of MPGN. Nat Rev Nephrol 8:634–642PubMedCrossRef

20.

Morath MA, Hörster F, Sauer SW (2013) Renal dysfunction in methylmalonic acidurias: review for the pediatric nephrologist. Pediatr Nephrol 28:227–235

21.

Morath MA, Okun JG, Müller IB, Sauer SW, Hörster F, Hoffmann GF, Kölker S (2008) Neurodegeneration and chronic renal failure in methylmalonic aciduria—a pathophysiological approach. J Inherit Metab Dis 31:35–43PubMedCrossRef

22.

McCully KS (2009) Chemical pathology of homocysteine. IV. Excitotoxicity, oxidative stress, endothelial dysfunction, and inflammation. Ann Clin Lab Sci 39:219–232PubMed

23.

Ke XD, Foucault-Bertaud A, Genovesio C, Dignat-George F, Lamy E, Charpiot P (2010) Homocysteine modulates the proteolytic potential of human arterial smooth muscle cells through a reactive oxygen species dependant mechanism. Mol Cell Biochem 335:203–210PubMedCrossRef

24.

Dionisio N, Jardin I, Salido GM, Rosado JA (2010) Homocysteine. Intracellular signaling and thrombotic disorders. Curr Med Chem 17:3109–3119PubMedCrossRef

25.

Bouts AH, Roofthooft MT, Salomons GS, Davin JC (2010) CD46-associated atypical hemolytic uremic syndrome with uncommon course caused by cblC deficiency. Pediatr Nephrol 25:2547–2548PubMedCrossRef

Title: Atypical glomerulopathy associated with the cblE inborn error of vitamin B12 metabolism
Authors: Erin A. Paul
Marta Guttenberg
Paige Kaplan
David Watkins
David S. Rosenblatt
James R. Treat
Bernard S. Kaplan
Publication date: 01-07-2013
Publisher: Springer-Verlag
Published in: Pediatric Nephrology / Issue 7/2013
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-013-2443-6

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Atypical glomerulopathy associated with the cblE inborn error of vitamin B₁₂ metabolism

Abstract

Background

Case-Diagnosis/Treatment

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Case-Diagnosis/Treatment

Conclusions

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