Fetal dilated cardiomyopathy: an unsuspected presentation of methylmalonic aciduria and hyperhomocystinuria, cblC type

Bie, Isabelle De; Nizard, Sonia; Mitchell, Grant A.

doi:10.1002/pd.2218

Cited by 35 publications

(28 citation statements)

References 31 publications

(39 reference statements)

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“…Congenital heart diseases include ventricular septal defect, pulmonary stenosis, dysplastic pulmonary valve, atrial defects, and mitral valve prolapse (Andersson et al 1999;Heinemann et al 2001;Tomaske et al 2001;Profitlich et al 2009). Cardiomyopathy and left ventricular noncompaction have been reported as well (Ogier de Baulny et al 1998;Longo et al 2005;De Bie et al 2009;Profitlich et al 2009). Other descriptions have reported infants with bronchiolitis-like symptoms, rapid deterioration, and death from cor pulmonale with dilated right ventricle.…”

Section: Early-onset Formmentioning

confidence: 94%

Cobalamin C defect: natural history, pathophysiology, and treatment

Martinelli

Deodato

Dionisi‐Vici

2010

J of Inher Metab Disea

124

138

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Cobalamin C (Cbl-C) defect is the most common inborn cobalamin metabolism error; it causes impaired conversion of dietary vitamin B12 into its two metabolically active forms, methylcobalamin and adenosylcobalamin. Cbl-C defect causes the accumulation of methylmalonic acid and homocysteine and decreased methionine synthesis. The gene responsible for the Cbl-C defect has been recently identified, and more than 40 mutations have been reported. MMACHC gene is located on chromosome 1p and catalyzes the reductive decyanation of CNCbl. Cbl-C patients present with a heterogeneous clinical picture and, based on their age at onset, can be categorized into two distinct clinical forms. Early-onset patients, presenting symptoms within the first year, show a multisystem disease with severe neurological, ocular, haematological, renal, gastrointestinal, cardiac, and pulmonary manifestations. Late-onset patients present a milder clinical phenotype with acute or slowly progressive neurological symptoms and behavioral disturbances. To improve clinical course and metabolic abnormalities, treatment of Cbl-C defect usually consists of a combined approach that utilizes vitamin B12 to increase intracellular cobalamin and to maximize deficient enzyme activities, betaine to provide a substrate for the conversion of homocysteine into methionine through betaine-homocysteine methyltransferase, and folic acid to enhance remethylation pathway. No proven efficacy has been demonstrated for carnitine and dietary protein restriction. Despite these measures, the long-term follow-up is unsatisfactory especially in patients with early onset, with frequent progression of neurological and ocular impairment. The unfavorable outcome suggests that better understanding of the pathophysiology of the disease is needed to improve treatment protocols and to develop new therapeutic approaches.

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Section: Early-onset Formmentioning

confidence: 94%

Cobalamin C defect: natural history, pathophysiology, and treatment

Martinelli

Deodato

Dionisi‐Vici

2010

J of Inher Metab Disea

124

138

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“…Biochemical and molecular genetic data (Table 2) have not uniformly been documented, although in several instances, the patients have had mutations and a clinical course consistent with "early onset" disease (Rosenblatt et al 1997). Cobalamin C disease has also been documented in a single patient who presented with dilated cardiomyopathy, diminished systolic function, hypocontractility of the left ventricle, and intrauterine growth retardation (De Bie et al 2009). Left ventricular noncompaction (LVNC) was not described in this infant.…”

Section: Discussionmentioning

confidence: 99%

“…At least 15 patients with cblC have been reported with cardiomyopathy (Table 1; Baumgartner et al 1979;Brandstetter et al 1990;Carmel et al 1980;Chenel et al 1993;De Bie et al 2009;Longo et al 2005;Geraghty et al 1992;Ogier de Baulny et al 1998;Profitlich et al 2009). However, the specifics regarding the type and echocardiographic manifestations of the cardiac lesions have not been fully delineated.…”

Section: Discussionmentioning

confidence: 99%

“…Malformations including congenital microcephaly and congenital heart diseases are frequently present (Andersson et al 1999). While the phenotypic spectrum of cblC disease is broad and age of onset is variable, encompassing prenatal and adult presentations, a prenatal cardiac presentation of right ventricular dilated cardiomyopathy in the third trimester has been documented in one infant with cblC disease (De Bie et al 2009). Here, we describe a patient with cblC disease who presented with the combination of hydrops fetalis and left ventricular noncompaction (LVNC), review the previous reports of cardiomyopathy in cblC disease, and highlight the need to consider the diagnosis of cblC disease in the setting of nonimmune hydrops fetalis, especially when cardiac disease is present in the fetus.…”

Section: Introductionmentioning

confidence: 99%

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Noncompaction of the Ventricular Myocardium and Hydrops Fetalis in Cobalamin C Disease

Tanpaiboon

Sloan

Callahan³

et al. 2012

JIMD Reports

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Cobalamin C disease (cblC), a form of combined methylmalonic acidemia and hyperhomocysteinemia caused by mutations in the MMACHC gene, may be the most common inborn error of intracellular cobalamin metabolism. The clinical manifestations of cblC disease are diverse and range from intrauterine growth retardation to adult onset neurological disease. The occurrence of structural heart defects appears to be increased in cblC patients and may be related to the function of the MMACHC enzyme during cardiac embryogenesis, a concept supported by the observation that Mmachc is expressed in the bulbis cordis of the developing mouse heart. Here we report an infant who presented with hydrops fetalis, ventricular dysfunction, and echocardiographic evidence of LVNC, a rare congenital cardiomyopathy. Metabolic evaluations, complementation studies, and mutation analysis confirmed the diagnosis of cblC disease. These findings highlight an intrauterine cardiac phenotype that can be displayed in cblC disease in association with nonimmune hydrops.

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“…Some patients detected by urine screening and for whom treatment is initiated in the first weeks of life have early-onset defect and have manifestations at birth or prenatally like cardiomyopathy (De Bie et al 2009). Therefore, newborn screening will not correct the defect in all patients, but arguably, early detection and treatment might influence neurodevelopment favorably in some individuals and will also detect other forms of methylmalonic aciduria.…”

Section: Pathophysiology Molecular Analyses and Treatment In Relatimentioning

confidence: 99%

A Highly Diverse Portrait: Heterogeneity of Neuropsychological Profiles in cblC Defect

et al. 2015

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Cobalamin C is a rare inborn disorder of metabolism that results in multisystemic abnormalities, including progressive visual deficits. Although the cellular pathophysiology of cblC is a field of active study, little attention has been dedicated to documenting the cognitive consequences of the defect. The neuropsychological assessment of nine individuals aged between 23 months and 24 years was conducted to establish cognitive profiles. Results reveal a marked heterogeneity, with intellectual functioning ranging from extremely low to average, and cognitive difficulties (e.g., attention) evidenced even in those who are not intellectually disabled. Central nervous system abnormalities and multisystem disease are likely to be major contributing factors to the observed cognitive impairments, with the presence of visual deficits constituting an additional impediment to normal cognitive development. This study underscores the importance of conduct ing in-depth neuropsychological assessments in individuals with cblC, the results of which may be particularly helpful for clinical management, guidance toward rehabilitation services, and educational/vocational planning.

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Fetal dilated cardiomyopathy: an unsuspected presentation of methylmalonic aciduria and hyperhomocystinuria, cblC type

Cited by 35 publications

References 31 publications

Cobalamin C defect: natural history, pathophysiology, and treatment

Cobalamin C defect: natural history, pathophysiology, and treatment

Noncompaction of the Ventricular Myocardium and Hydrops Fetalis in Cobalamin C Disease

A Highly Diverse Portrait: Heterogeneity of Neuropsychological Profiles in cblC Defect

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