Clinical, Biochemical, and Molecular Presentation in a Patient with the cblD-Homocystinuria Inborn Error of Cobalamin Metabolism

Atkinson, Celia; Miousse, Isabelle R.; Watkins, David; Rosenblatt, David S.; Raiman, Julian

doi:10.1007/8904_2014_340

Cited by 14 publications

(7 citation statements)

References 14 publications

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“…References: Fischer et al 2014; Al Essa et al 1999; Al Tawari et al 2002; Alfadhel et al 2011; Andersson et al 1999; Andersson and Shapira 1998; Arai and Osaka 2011; Arn et al 1998; Atkinson et al 2014; Augoustides-Savvopoulou et al 1999; Backe et al 2013; Baumgartner et al 1979a; Baumgartner et al 1979b; Beauchamp et al 2009; Bellini et al 1992; Ben-Shachar et al 2012; Biancheri et al 2002; Biancheri et al 2001; Biotti et al 2014; Birnbaum et al 2008; Bishop et al 2008; Brandstetter et al 1990; Broomfield et al 2014; Brunel-Guitton et al 2010; Brunelli et al 2002; Cappuccio et al 2014; Carmel et al 1980; Carmel et al 1988; Carrillo-Carrasco et al 2009; Carrillo-Carrasco et al 2012a, b; Cerone et al 2000; Chang et al 2011; Clayton et al 1986; Coelho et al 2008; Cogan et al 1980; D’Aco et al 2014; D’Alessandro et al 2010; De Bie et al 2009; Dionisi-Vici et al 2013; Ellaway et al 1998; Engelbrecht et al 1997; Enns et al 1999; Fuchs et al 2012; Geraghty et al 1992; Gerth et al 2008; Goodman et al 1970; Goyette et al 1996; Goyette et al 1995; Goyette et al 1994; Grant et al 2009; Grünert et al 2011; Guigonis et al 2005; Gulati et al 1997; Haan et al 1985; Harding et al 1997; Harpey et al 1981; Haworth et al 1993; Holme and Ronge 1989; Howard et al 1997; Huemer et al 2005, 2014, 2015a, b; Hyland et al 1988; Kanwar et al 1976; Kind et al 2002; Lesesve and Latger-Cannard 2013; Levy et al 1970; Longo et al 2005; Lossos...…”

Section: Methodsmentioning

confidence: 99%

Guidelines for diagnosis and management of the cobalamin‐related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

Huemer

Diodato

Schwahn

et al. 2016

J of Inher Metab Disea

242

368

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BackgroundRemethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions.ObjectiveTo summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management.Data sourcesReview, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach.Key recommendationsWe strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-016-9991-4) contains supplementary material, which is available to authorised users.

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Section: Methodsmentioning

confidence: 99%

Guidelines for diagnosis and management of the cobalamin‐related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

Huemer

Diodato

Schwahn

et al. 2016

J of Inher Metab Disea

242

368

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“…Although previous case reports of cblD defect patients have reported the presence of developmental delay, learning disabilities, and cognitive impairment [2,4,7,8,51,63,64], our study is the first one that includes a comprehensive neuropsychological evaluation to measure a variety of cognitive domains in a patient with the cblD disease. Our results show that the patient presented low scores in attention, memory, speed of information processing, inhibitory control, mental flexibility, and language measures, in accordance with studies with vitamin B12-deficient patients [58,65].…”

Section: Discussionmentioning

confidence: 99%

Brain Circuit Alterations and Cognitive Disability in Late-Onset Cobalamin D Disorder

Heras

Diez

Jiménez-Marín

et al. 2020

JCM

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Neuroimaging studies describing brain circuits’ alterations in cobalamin (vitamin B12)-deficient patients are limited and have not been carried out in patients with inborn errors of cobalamin metabolism. The objective of this study was to assess brain functionality and brain circuit alterations in a patient with an ultra-rare inborn error of cobalamin metabolism, methylmalonic aciduria, and homocystinuria due to cobalamin D disease, as compared with his twin sister as a healthy control (HC). We acquired magnetic resonance imaging (including structural, functional, and diffusion images) to calculate brain circuit abnormalities and combined these results with the scores after a comprehensive neuropsychological evaluation. As compared with HC, the patient had severe patterns of damage, such as a 254% increment of ventricular volume, pronounced subcortical and cortical atrophies (mainly at striatum, cingulate cortex, and precuneus), and connectivity alterations at fronto-striato-thalamic circuit, cerebellum, and corpus callosum. In agreement with brain circuit alterations, cognitive deficits existed in attention, executive function, inhibitory control, and mental flexibility. This is the first study that provides the clinical, genetic, neuroanatomical, neuropsychological, and psychosocial characterization of a patient with the cobalamin D disorder, showing functional alterations in central nervous system motor tracts, thalamus, cerebellum, and basal ganglia, that, as far as we know, have not been reported yet in vitamin B12-related disorders.

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“…In the rst case there will be the forms of methylmalonic acidemia due to coenzyme de ciency, which respond in part to therapy with B 12 (ca. 10-20%), while the methylcobalamin de ciency blocks the methylation of homocysteinethus causing massive homocystinuria (6). The activity of methionine synthetase also requires the presence of some intermediates of the folate metabolism.…”

Section: Introductionmentioning

confidence: 99%

Long-term Outcome of a Patient With Transcobalamin Deficiency Caused by Tcn2 Mutation: A Case Report

Martino

Magenta

Troccoli

et al. 2020

Preprint

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Background:Transcobalamin deficiency is a rare autosomal recessive inborn error of cobalamin transport (prevalence: <1/1000000)whichclinically manifests in early infancy. Case presentation:We describe the case of a 30 year old woman who at the age of 30 days presented with the classical clinical and laboratory signs of an inborn error of vitamin B12 metabolism. Family history revealed a sister who died at the age of 3 months with a similar clinical syndrome and with pancytopenia.Shewas started on empirical intramuscular (IM) cobalamin supplements (injections of hydroxocobalamin 1 mg/day for 1 week and then 1 mg twice a week) and several transfusions of washed and concentrated red blood cells.With thesetreatments a clear improvement in symptoms was observed, with the disappearance of vomiting, diarrhea and normalization of the full blood count.At 8 years of age injections were stopped for 3 monthscausing the reappearance of megaloblastic anemia.IM hydroxocobalamin was then restartedsine die.The definitive diagnosis could only be established at 29 years of age when a genetic evaluation revealed homozygous nonsense variation in exon 8 of the TCN2 gene.Currently she is a 30-year old healthy lady taking 1 mg of IM hydroxocobalamin once a week.Conclusions: Our case report highlights that early detection of TC deficiency and early initiation of aggressive IM treatment is likely associated with disease control and an overall favorable outcome.

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Clinical, Biochemical, and Molecular Presentation in a Patient with the cblD-Homocystinuria Inborn Error of Cobalamin Metabolism

Cited by 14 publications

References 14 publications

Guidelines for diagnosis and management of the cobalamin‐related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

Guidelines for diagnosis and management of the cobalamin‐related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

Brain Circuit Alterations and Cognitive Disability in Late-Onset Cobalamin D Disorder

Long-term Outcome of a Patient With Transcobalamin Deficiency Caused by Tcn2 Mutation: A Case Report

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