Titration of betaine therapy to optimize therapy in an infant with 5,10-methylenetetrahydrofolate reductase deficiency

Uçar, Sema Kalkan; Köroğlu, Özge Altun; Berk, Ömer; Yalaz, Mehmet; Kültürsay, Nilgün; Blom, Henk J.; Çöker, Mahmut

doi:10.1007/s00431-009-0997-x

Cited by 12 publications

(10 citation statements)

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“…Plasma betaine levels indicated satisfactory intestinal absorption of betaine (data not shown). Nevertheless, although little is known about betaine pharmacokinetics (Schwahn et al 2003), more frequent dosing of orally administered betaine (six divided doses) normalized tHCy levels in a infant with MTHFR deficiency, even before 1 year of age (Ucar et al 2010). 5.…”

Section: Available Treatmentsmentioning

confidence: 97%

Isolated remethylation disorders: do our treatments benefit patients?

Schiff

Benoist

Tilea

et al. 2010

J of Inher Metab Disea

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Deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR), the very rare methionine synthase reductase (CblE) and methionine synthase (CblG) defects, and the recently identified CblD-variant-1 defect are primary remethylation defects characterized by an isolated defect in methionine synthesis without methylmalonic aciduria. The clinical signs are mainly neurological, and hematological signs are seen in CblE, CblG, and CblD-variant-1 defects. Patients with neonatal or early-onset disease exhibit acute neurological distress. Infants and children have unspecific mental retardation, often with acquired microcephaly. Without appropriate therapy, they may experience acute or rapidly progressive neurological deterioration, which may be fatal. Adolescents and adults show normal development or mild developmental delay initially and then experience rapid neurological or behavioral deterioration. A few patients may have signs of subacute combined degeneration of the spinal cord. Adults may be asymptomatic or present with isolated thromboembolism. All patients with suspected remethylation disorders should receive emergency treatment with parenteral administration of hydroxocobalamin and folate supplements combined with betaine orally. The long-term treatment of CblE, CblG, and CblD-variant-1 defects consists of parenterally administered hydroxocobalamin and orally administered folate and betaine supplements, whereas patients with MTHFR deficiency require long-term oral folate and betaine supplements. Long-term oral methionine therapy should also be considered. Early treatment may lead to a favorable outcome with developmental recovery and prevention of further neurological deterioration. In contrast, most late-treated patients have severe and irreversible neuromotor impairments. Hematological abnormalities are easily corrected.

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Section: Available Treatmentsmentioning

confidence: 97%

Isolated remethylation disorders: do our treatments benefit patients?

Schiff

Benoist

Tilea

et al. 2010

J of Inher Metab Disea

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“…The knowledge about betaine pharmacokinetics is limited (Schwahn et al 2003). It has been suggested that frequent administration of a moderate dose may provide clinical and biochemical benefit (Ucar et al 2010). Betaine or OHCbl alone may not result in sufficient metabolic control, but they seem to have synergistic effects (Bartholomew et al 1988).…”

Section: The Effects Of Treatment On Clinical Outcomementioning

confidence: 99%

“…There have been some reports describing the use of folic acid (5–80 mg/day) with good (Al Tawari et al 2002; Munoz et al 2015) or poor (Holme and Ronge 1989; Ucar et al 2010) response. A dose–response relationship was not observed (Holme and Ronge 1989).…”

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

244

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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“…Hastamız-da klinik, biyokimyasal ve MRI verileri neticesinde MTHFR eksikliğinden şüphe edilerek periferik kan DNA analizi Hollanda'dan VU Üniversitesi Medikal Merkezi Metabolizma Laboratuvarı'nda çalıştı-rılmıştır. Daha önce rapor edilmiş bir missense mutasyon olan c.1015T>G (p.trp339Gly) mutasyonu hastamızda homozigot olarak saptanmıştır (9,10). Tanıyı doğrulamak adına anne ve babanın c.1015T>G için heterozigot taşıyıcı oldukları göste-rilmiştir.…”

Section: Introductionunclassified