Clinical characteristics of hemolytic uremic syndrome secondary to cobalamin C disorder in Chinese children

Li, Qiliang; Song, Wenqi; Peng, Xiaoxia; Liu, Xiaorong; He, Lejian; Fu, Libing

doi:10.1007/s12519-015-0032-4

Cited by 10 publications

(5 citation statements)

References 23 publications

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“… 31 This confirms the wide heterogeneity of cblC disease, and that the diagnosis has to be evoked even in the absence of neurologic damage. 32 Likewise, only 1 patient presented with PAH in our study, but several cases of PAH during cblC deficiency have been reported, frequently associated with TMA. 33 , 34 …”

Section: Discussionmentioning

confidence: 46%

Cobalamin C Deficiency Induces a Typical Histopathological Pattern of Renal Arteriolar and Glomerular Thrombotic Microangiopathy

Lemoine

François

Grangé

et al. 2018

Kidney International Reports

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IntroductionCobalamin C (cblC) deficiency is the most common inborn error of vitamin B12 metabolism. Renal failure attributed to thrombotic microangiopathy (TMA) has occasionally been described in the late-onset presentation of cblC deficiency, but kidney lesions associated with cblC deficiency remain poorly defined. This study aims to describe the characteristics of kidney disease in cblC deficiency, and to provide a comparative histological analysis with cblC-independent renal TMA.MethodsWe performed a multicenter retrospective study including 7 patients with cblC deficiency and 16 matched controls with cblC-independent TMA. The patients included were aged 6 to 26 years at the time of the first manifestations. All patients presented with acute renal failure, proteinuria, and hemolysis; 5 patients required dialysis.ResultsThe histological study revealed arteriolar and glomerular TMA in all patients. After comparison with the cblC-independent TMA control group, a vacuolated aspect of the glomerular basement membrane and the intensity of glomerular capillary wall IgM deposits were more present in cblC deficiency patients than in controls. Six patients were treated with hydroxycobalamin. All of them improved, with disappearance of hemolysis, and 3 of the 4 patients requiring renal replacement therapy were weaned off dialysis.ConclusionThis study provides a precise description of kidney pathology in cblC deficiency. Due to major therapeutic implications, we suggest that patients with renal TMA be screened for cblC deficiency regardless of age, particularly when the kidney biopsy provides evidence of long-lasting TMA, including a vacuolated aspect of the glomerular basement membrane and glomerular capillary wall IgM deposition.

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Section: Discussionmentioning

confidence: 46%

Cobalamin C Deficiency Induces a Typical Histopathological Pattern of Renal Arteriolar and Glomerular Thrombotic Microangiopathy

Lemoine

François

Grangé

et al. 2018

Kidney International Reports

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“…We identified 36 patients ([14, 21–38], including one unpublished patient) with established cblC defect and renal involvement. Diagnosis of MMACHC was confirmed biochemically in 34 patients and genetically in 18 (Table 3; for individual data, see Table S1).…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2016

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Methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type, is the most common genetic type of functional cobalamin (vitamin B12) 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 materialThe 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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“…The kidney excretion functions of the cblC-MMA patients were affected by high concentrations of methylmalonic acid and homocysteine. The mechanisms of renal injury of cblC-MMA patients included that homocysteine caused vascular coagulation and glomerular vascular injury ( 36 , 37 ) and methylmalonic acid induced renal tubular acidosis ( 38 , 39 ). In this study, we found the levels of urea were obviously higher than normal children, which indicated the renal injury in cblC-MMA.…”

Section: Discussionmentioning

confidence: 99%

Methylmalonic acid levels in serum, exosomes, and urine and its association with cblC type methylmalonic acidemia-induced cognitive impairment

et al. 2022

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BackgroundThe cblC type methylmalonic acidemia is the most common methylmalonic acidemia (MMA) in China. The biochemical characteristics of this disease include elevated methylmalonic acid and homocysteine (HCY), increased propionylcarnitine (C3), decreased free carnitine (C0). In this study, we aimed to clarify the roles of these biomarkers in cblC-MMA induced cognitive impairment and evaluate the capacity of methylmalonic acid in different fluids or exosomes to distinguish cblC-MMA induced cognitive impairment.Methods15 non-inherited hyperhomocysteinemia (HHcy) patients, 42 cblC-MMA patients and 57 age- and sex-matched healthy children were recruited in this study. The levels of HCY were detected by an automatic immune analyzer. The levels of acylcarnitines and methylmalonic acid were detected by tandem mass spectrometer.ResultsThe main findings were all biomarkers as HCY, acylcarnitines and methylmalonic acid had capacities for distinguishing patients with cblC-MMA induced cognitive impairment from healthy children. The methylmalonic acid in different fluids or exosomes had good performances for distinguishing patients with cblC-MMA induced cognitive impairment from HHcy patients. The methylmalonic acid in serum exosomes and neuronal-derived exosomes were able to distinguishing cblC-MMA patients with cognitive impairment from patients without cognitive impairment. The methylmalonic acid in neuronal-derived exosomes might be helpful to evaluate the severity of cblC-MMA induced cognitive impairment.DiscussionMethylmalonic acid levels in serum exosomes, especially in serum neuronal-derived exosomes, serve as potential biomarkers for distinguishing cblC-MMA induced cognitive impairment.

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Clinical characteristics of hemolytic uremic syndrome secondary to cobalamin C disorder in Chinese children

Cited by 10 publications

References 23 publications

Cobalamin C Deficiency Induces a Typical Histopathological Pattern of Renal Arteriolar and Glomerular Thrombotic Microangiopathy

Cobalamin C Deficiency Induces a Typical Histopathological Pattern of Renal Arteriolar and Glomerular Thrombotic Microangiopathy

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

Methylmalonic acid levels in serum, exosomes, and urine and its association with cblC type methylmalonic acidemia-induced cognitive impairment

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