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Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity

Methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type, is the most common genetic type of functional cobalamin (vitamin B(12)) deficiency. This metabolic disease is characterized by marked heterogeneity of neurocognitive disease (microcephaly, seizures, developmental delay, ataxia, hypo...

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Autores principales: Beck, Bodo B., van Spronsen, FrancJan, Diepstra, Arjan, Berger, Rolf M. F., Kömhoff, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368212/
https://www.ncbi.nlm.nih.gov/pubmed/27289364
http://dx.doi.org/10.1007/s00467-016-3399-0
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author Beck, Bodo B.
van Spronsen, FrancJan
Diepstra, Arjan
Berger, Rolf M. F.
Kömhoff, Martin
author_facet Beck, Bodo B.
van Spronsen, FrancJan
Diepstra, Arjan
Berger, Rolf M. F.
Kömhoff, Martin
author_sort Beck, Bodo B.
collection PubMed
description Methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type, is the most common genetic type of functional cobalamin (vitamin B(12)) deficiency. This metabolic disease is characterized by marked heterogeneity of neurocognitive disease (microcephaly, seizures, developmental delay, ataxia, hypotonia) and variable extracentral nervous system involvement (failure to thrive, cardiovascular, renal, ocular) manifesting predominantly early in life, sometimes during gestation. To enhance awareness and understanding of renal disease associated with cblC defect, we studied biochemical, genetic, clinical, and histopathological data from 36 patients. Consistent clinical chemistry features of renal disease were intravascular hemolysis, hematuria, and proteinuria in all patients, with nephrotic-range proteinuria observed in three. Renal function ranged from normal to renal failure, with eight patients requiring (intermittent) dialysis. Two thirds were diagnosed with atypical (diarrhea-negative) hemolytic uremic syndrome (HUS). Renal histopathology analyses of biopsy samples from 16 patients revealed glomerular lesions typical of thrombotic microangiopathy (TMA). Treatment with hydroxycobalamin improved renal function in the majority, including three in whom dialysis could be withdrawn. Neurological sequelae were observed in 44 % and cardiopulmonary involvement in 39 % of patients, with half of the latter group demonstrating pulmonary hypertension. Mortality reached 100 % in untreated patients and 79 and 56 % in those with cardiopulmonary or neurological involvement, respectively. In all patients presenting with unclear intravascular hemolysis, hematuria, and proteinuria, cblC defect should be ruled out by determination of blood/plasma homocysteine levels and/or genetic testing, irrespective of actual renal function and neurological status, to ensure timely diagnosis and treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00467-016-3399-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-53682122017-04-11 Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity Beck, Bodo B. van Spronsen, FrancJan Diepstra, Arjan Berger, Rolf M. F. Kömhoff, Martin Pediatr Nephrol Review Methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type, is the most common genetic type of functional cobalamin (vitamin B(12)) deficiency. This metabolic disease is characterized by marked heterogeneity of neurocognitive disease (microcephaly, seizures, developmental delay, ataxia, hypotonia) and variable extracentral nervous system involvement (failure to thrive, cardiovascular, renal, ocular) manifesting predominantly early in life, sometimes during gestation. To enhance awareness and understanding of renal disease associated with cblC defect, we studied biochemical, genetic, clinical, and histopathological data from 36 patients. Consistent clinical chemistry features of renal disease were intravascular hemolysis, hematuria, and proteinuria in all patients, with nephrotic-range proteinuria observed in three. Renal function ranged from normal to renal failure, with eight patients requiring (intermittent) dialysis. Two thirds were diagnosed with atypical (diarrhea-negative) hemolytic uremic syndrome (HUS). Renal histopathology analyses of biopsy samples from 16 patients revealed glomerular lesions typical of thrombotic microangiopathy (TMA). Treatment with hydroxycobalamin improved renal function in the majority, including three in whom dialysis could be withdrawn. Neurological sequelae were observed in 44 % and cardiopulmonary involvement in 39 % of patients, with half of the latter group demonstrating pulmonary hypertension. Mortality reached 100 % in untreated patients and 79 and 56 % in those with cardiopulmonary or neurological involvement, respectively. In all patients presenting with unclear intravascular hemolysis, hematuria, and proteinuria, cblC defect should be ruled out by determination of blood/plasma homocysteine levels and/or genetic testing, irrespective of actual renal function and neurological status, to ensure timely diagnosis and treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00467-016-3399-0) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2016-06-11 2017 /pmc/articles/PMC5368212/ /pubmed/27289364 http://dx.doi.org/10.1007/s00467-016-3399-0 Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review
Beck, Bodo B.
van Spronsen, FrancJan
Diepstra, Arjan
Berger, Rolf M. F.
Kömhoff, Martin
Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity
title Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity
title_full Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity
title_fullStr Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity
title_full_unstemmed Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity
title_short Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity
title_sort renal thrombotic microangiopathy in patients with cblc defect: review of an under-recognized entity
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368212/
https://www.ncbi.nlm.nih.gov/pubmed/27289364
http://dx.doi.org/10.1007/s00467-016-3399-0
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