Prenatal Vitamin B12 Therapy of a Fetus With Methylcobalamin Deficiency (Cobalamin E Disease)

Rosenblatt, D.; Schmutz, SheilaM.; Cooper, Bernard A.; Zaleski, W; Casey, R.G.

doi:10.1016/s0140-6736(85)92433-x

Cited by 57 publications

(26 citation statements)

References 9 publications

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“…Studies using intact cultured fibroblasts from these patients also yielded mostly similar results (8,(10)(11)(12)(13). In all cases, synthesis of MeCbl from labeled precursor and intact cell methionine biosynthesis were deficient.…”

Section: Discussionmentioning

confidence: 66%

“…Synthesis of MeCbl from 57Co-labeled cyanocobalamin and intact cell methionine biosynthesis, measured by the incorporation of label from 5-['4C]-methyltetrahydrofolate into acid-precipitable material, were decreased in each ofthe mutant strains compared with control values. Synthesis of AdoCbl and incorporation of label from ['4C]propionate into acid-precipitable material, an indirect measure of methylmalonylCoA mutase activity, were normal (7,8,(10)(11)(12)(13). Table I shows the results of assay of methionine synthase activity in extracts of control and MeCbl-deficient fibroblasts.…”

Section: Resultsmentioning

confidence: 99%

“…In 1984, a patient was described with an inborn error of cobalamin metabolism that caused decreased synthesis of MeCbl alone without any effect on AdoCbl synthesis (7,8 (13).…”

Section: Introductionmentioning

confidence: 99%

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Genetic heterogeneity among patients with methylcobalamin deficiency. Definition of two complementation groups, cblE and cblG.

Watkins¹,

Rosenblatt²

1988

J. Clin. Invest.

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A number of patients with megaloblastic anemia and homocystinuria associated with low levels of methylcobalamin synthesis in cultured cells have been recognized. Methionine biosynthesis by intact cells, as determined by incorporation of label from 5-I14Clmethyl-tetrahydrofolate into acid-precipitable material, was deficient in cultured skin fibroblasts that were derived from all of these patients. In one group of patients, activity of the methylcobalamin-dependent enzyme, methionine synthase, in cell extracts was within the normal range when the enzyme was assayed under standard conditions. In a second group of patients, methionine synthase activity was decreased under the same assay conditions. Genetic complementation analysis demonstrated the existence of two complementation classes that corresponded to these two groups of patients. The designation cblE has previously been proposed for the mutation in a patient with methylcobalamin deficiency and normal methionine synthase activity. We propose the designation cblG for the mutation in those patients with methylcobalamin deficiency and decreased synthase activity. The results of these studies suggest that the products of at least two loci are required for cobalamin-dependent methionine biosynthesis in mammalian cells.

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Section: Discussionmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Genetic heterogeneity among patients with methylcobalamin deficiency. Definition of two complementation groups, cblE and cblG.

Watkins¹,

Rosenblatt²

1988

J. Clin. Invest.

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“…[2][3][4]20,29 Although treatment strategies for this group of disorders may differ slightly for each specific entity, the same general principles are applicable to the entire group and there is no tangible risk of harm by prescription of a combination treatment of all medications immediately after the finding of elevated tHcy in dried blood spots and a rapid confirmation in plasma, the latter being a routinely available test.…”

Section: Discussionmentioning

confidence: 99%

“…Early diagnosis and treatment of at least severe MTHFR deficiency lead to either reduction or even prevention of symptoms if initiated at the earliest possible time in the first month of life before irreversible central nervous system central nervous system (CNS) damage occurs. [2][3][4] Recently, an approach utilizing low…”

Section: Introductionmentioning

confidence: 99%

Outcomes of four patients with homocysteine remethylation disorders detected by newborn screening

Wong

Tortorelli

Bishop

et al. 2016

Genetics in Medicine

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Purpose:We evaluated the clinical outcome in homocysteine remethylation disorders following newborn screening (NBS) and initiation of early specific treatment. Methods:Five patients with remethylation disorders were included in this study. Results:Two asymptomatic patients (one with cblG and one with cblE) were identified by NBS using an approach that combines a postanalytical interpretive tool (available on the Region 4 Stork (R4S) collaborative project website, http://www.clir-r4s.org) and a second-tier test for total homocysteine determination. Both the initial screening and the second-tier test are performed on the same blood spot, with no additional patient contact, resulting in no false-positive outcomes. Two additional patients with methylenetetrahydrofolate reductase deficiency were detected by NBS using low methionine as a marker.Although already symptomatic despite the early diagnosis, the latter two patients greatly improved with treatment and their outcomes are compared with that of another patient with methylenetetrahydrofolate reductase deficiency and significant morbidity who was diagnosed clinically at 3 months of age. Conclusion:Early detection by NBS and timely and specific treatment considerably improve at least short-term outcomes of homocysteine remethylation disorders. When a remethylation disorder is suspected, group-specific treatment could be started prior to the completion of in vitro confirmatory testing because all disorders from this group require similar intervention.

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Functional methionine synthase deficiency due to cblG disorder: A report of two patients and a review

et al. 1997

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Functional methionine synthase deficiency due to abnormal methylcobalamin metabolism causes megaloblastic anemia, moderate to severe developmental delay, lethargy, and anorexia in association with homocystinuria. Patients with this disorder of cobalamin metabolism can be classified into two separate groups, cblE or cblG, primarily on the basis of complementation analysis with cultured skin fibroblasts. We describe two unrelated boys, ages 3 and 5 years, with the cblG defect in methylcobalamin synthesis. Both children presented with severe developmental delay, lethargy, anorexia, and megaloblastic anemia. The diagnosis of homocystinuria was delayed in each case due to difficulties with detection of small amounts of homocystine in physiologic samples. The clinical course of cblG disease is favorably altered by treatment with intramuscular hydroxycobalamin. Megaloblastosis in the presence of adequate supplies of cobalamin and folate in the blood must alert the clinician to the possibility of functional methionine synthase deficiency and should prompt a careful search for associated biochemical hallmarks, including homocystinuria/emia.

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Prenatal Vitamin B12 Therapy of a Fetus With Methylcobalamin Deficiency (Cobalamin E Disease)

Cited by 57 publications

References 9 publications

Genetic heterogeneity among patients with methylcobalamin deficiency. Definition of two complementation groups, cblE and cblG.

Genetic heterogeneity among patients with methylcobalamin deficiency. Definition of two complementation groups, cblE and cblG.

Outcomes of four patients with homocysteine remethylation disorders detected by newborn screening

Functional methionine synthase deficiency due to cblG disorder: A report of two patients and a review

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