Tier 4 — mechanistic

Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency

Eugene F Diekman, Tom J de Koning, Nanda M Verhoeven-Duif, Maroeska M Rovers, Peter M van Hasselt
JAMA neurology 2014 71(2):188-194

Bibliography

PubMed
PMID 24323041
DOI
10.1001/jamaneurol.2013.4915
Funding
Funding was not specified in the indexed record or accessible funding metadata.
Competing interests
A competing-interest declaration was not available in the indexed record or accessible disclosure metadata.

Study snapshot

DesignSystematic analysis of case reports
ModelHuman participants
Sample36 patients across 15 case reports/series
InterventionEarly versus delayed or absent betaine treatment in severe MTHFR deficiency
DurationVariable follow-up; literature through 2012
EndpointsSurvival; Psychomotor development; Treatment timing

What the study showed, in plain terms

Published in 2014, this source examined prescription betaine and inherited metabolic disorders. Design: Systematic analysis of case reports. Sample/model: 36 patients across 15 case reports/series. The exposure or intervention was Early versus delayed or absent betaine treatment in severe MTHFR deficiency. Follow-up or treatment period: Variable follow-up; literature through 2012.

All five early-treated patients survived with normal reported psychomotor development; deaths and impairment clustered in untreated or later-treated cases.

Evidence comes from case reports with selection and timing biases, not randomized trials. Severe MTHFR deficiency is distinct from common polymorphisms.

Continue with TMG Data Center

Continue with TMG, Methylation and MTHFR: Understanding the Evidence

Key findings

  • All five early-treated patients survived with normal reported psychomotor development; deaths and impairment clustered in untreated or later-treated cases.
  • The recorded outcome domains were Survival; Psychomotor development; Treatment timing.

What this study can and cannot tell us

  • Evidence comes from case reports with selection and timing biases, not randomized trials. Severe MTHFR deficiency is distinct from common polymorphisms.
  • A case report or series cannot estimate how often an event occurs or establish causality without alternative explanations and a suitable comparator.
  • Source basis: Indexed abstract and bibliographic data. Missing method details, funding information or participant denominators are not inferred.

Related papers in the corpus

Tier 2
First Revision of the Guidelines for the Diagnosis and Management of Remethylation Disorders
Giorgia Olivieri et al. · Journal of inherited metabolic disease · 2026
Tier 2
Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency
Andrew A M Morris et al. · Journal of inherited metabolic disease · 2017
Tier 4
Postauthorization safety study of betaine anhydrous
Ulrike Mütze et al. · Journal of inherited metabolic disease · 2022
Tier 4
Cystathionine beta synthase deficiency and brain edema associated with methionine excess under betaine supplementation: Four new cases and a review of the evidence
Bernd C Schwahn et al. · JIMD reports · 2020
Tier 2
Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial
Apolline Imbard et al. · Orphanet journal of rare diseases · 2022

Citation network

Articles citing this research paper

1 article

Biohack Blueprint analyses that reference this study in their evidence base.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology