Successful intrauterine treatment of a patient with cobalamin C defect

Trefz, Friedrich K.; Scheible, D.; Frauendienst-Egger, G.; Huemer, Martina; Suomala, Terttu; Fowler, Brian; Haas, Dorothea; Baumgartner, Matthias R.

doi:10.1016/j.ymgmr.2016.01.005

Cited by 19 publications

(14 citation statements)

References 18 publications

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“…This has prompted therapeutic trials of hydroxycobalamin in fetuses known to have the disorder. 20,21 In our cohort, the lowest recorded methionine and highest homocysteine values were correlated with neurodevelopmental outcomes. These extreme values generally occurred in the neonatal period prior to therapy initiation and therefore may reflect the degree of metabolic derangement in utero.…”

Section: Discussionmentioning

confidence: 53%

Efficacy of early treatment in patients with cobalamin C disease identified by newborn screening: a 16-year experience

Ahrens‐Nicklas

Whitaker

Kaplan

et al. 2017

Genetics in Medicine

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Purpose Despite implementation of newborn screening (NBS), outcomes in cobalamin C disease (cblC) remain poor. Therapy with hydroxycobalamin and betaine is widely used, but dietary recommendations vary among metabolic centers. We present a longitudinal analysis of the relationship between metabolic control, diet, and outcomes in a cohort of cblC patients. Methods We completed a retrospective analysis of 12 patients with cblC referred for abnormal NBS results and followed in our center between 1999 and 2015. Results Of the patients, 87.5% had intellectual disability and 75% had retinopathy; 16.7% had one episode of mild acidosis. However, no patients manifested major metabolic decompensation. Developmental outcomes correlated more closely with initial metabolic abnormalities than with long-term metabolic control. Increased intake of medical foods resulted in better control but also perturbations in the ratios of essential amino acids and lower z-scores for head circumference. We found no relationship between diet and cognitive outcomes. Conclusions Although dietary therapy for cblC patients improves metabolic control, few patients experience metabolic decompensation regardless of diet. Increased incomplete protein intake is not correlated with improvements in outcomes. Overall, outcomes are poor despite early initiation of therapy and regardless of the dietary strategy used.

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Section: Discussionmentioning

confidence: 53%

Efficacy of early treatment in patients with cobalamin C disease identified by newborn screening: a 16-year experience

Ahrens‐Nicklas

Whitaker

Kaplan

et al. 2017

Genetics in Medicine

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“…For cblC disease, Trefz et al (2016) report a favourable outcome of a pregnancy with an affected fetus (sibling to a severely affected child) after treatment of the mother with high-dose OHCbl (30 mg/week) and 5 mg/day folic acid from week 15 of pregnancy. Prenatal treatment with lower OHCbl doses resulted in biochemical improvement.…”

Section: The Effects Of Treatment On Clinical Outcomementioning

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

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233

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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“…Intrauterine therapy is used to treat fetuses with MMA. Trefz et al 31 reported a patient with MMA in whom prenatal maternal treatment from week 15 of pregnancy prevented disease manifestation in a girl who is currently 11 years old with a normal IQ. However, we did not offer prenatal B12 therapy to the mother of family 7, and the pregnant woman chose to terminate the pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia

Zhang

Wang

Shen

et al. 2020

Sci Rep

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Methylmalonic acidemia (MMA)-affected patients may have developmental, hematological, neurological, metabolic, ophthalmological, and dermatological clinically abnormal findings. This study aimed to identify mutations in 13 Chinese MMA cases. We provided genetic counseling, treatment, and prenatal diagnosis for the families with MMA. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was performed and the results were confirmed by gas chromatography and mass spectrometry (GC/MS). Variant screening in probands was performed by targeted next-generation sequencing. Identified variants were confirmed by Sanger sequencing. Of these 13 MMA cases, seven were isolated MMA, and among them, six were caused by variants in MMUT and one was caused by a variant in MCEE . The other six cases were MMA with homocystinuria, which was caused by variants in MMACHC . We found six novel variants in three MMA-causing genes as follows: c.2008G>A, c.301_302insTA, c.984delC, and c.319A>T of MMUT ; c.445T>C of MMACHC ; and c.296T>C of MCEE . We provided prenatal diagnosis for two families with MMA at their next pregnancy, and one family had a healthy newborn. In conclusion, our findings expand the spectrum of genotypes in MMA. Effective genetic counseling is required to allow awareness of the patients’ families that MMA disease is treatable and a good prognosis can be obtained.

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Successful intrauterine treatment of a patient with cobalamin C defect

Cited by 19 publications

References 18 publications

Efficacy of early treatment in patients with cobalamin C disease identified by newborn screening: a 16-year experience

Efficacy of early treatment in patients with cobalamin C disease identified by newborn screening: a 16-year experience

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

Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia

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