Universität zu Köln

Beck, Bodo B., van Spronsen, FrancJan, Diepstra, Arjan ORCID: 0000-0001-9239-1050, Berger, Rolf M. F. and Komhoff, Martin ORCID: 0000-0002-6499-5313 (2017). Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity. Pediatr. Nephrol., 32 (5). S. 733 - 742. NEW YORK: SPRINGER. ISSN 1432-198X

Full text not available from this repository.

Abstract

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 Treatment with hydroxycobalamin improved renal function in the majority, including three in whom dialysis could be withdrawn.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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Beck, Bodo B. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Spronsen, FrancJan UNSPECIFIED UNSPECIFIED UNSPECIFIED Diepstra, Arjan UNSPECIFIED orcid.org/0000-0001-9239-1050 UNSPECIFIED Berger, Rolf M. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Komhoff, Martin UNSPECIFIED orcid.org/0000-0002-6499-5313 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-233011
DOI:	10.1007/s00467-016-3399-0
Journal or Publication Title:	Pediatr. Nephrol.
Volume:	32
Number:	5
Page Range:	S. 733 - 742
Date:	2017
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-198X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEMOLYTIC-UREMIC-SYNDROME; COBALAMIN C DEFICIENCY; METHYLMALONIC ACIDURIA; CLINICAL CHARACTERISTICS; PULMONARY-HYPERTENSION; CONGENITAL DEFECT; NITROUS-OXIDE; METABOLISM; HOMOCYSTINURIA; MUTATIONS Multiple languages Pediatrics; Urology & Nephrology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23301