Tier 4 — mechanistic

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, Thomas Scheffner, Hedwig Stepman, Peter Verloo, Anibh M Das, Janice Fletcher, Henk J Blom, Jean-Francois Benoist, Bruce A Barshop, Jaime J Barea, Annette Feigenbaum
JIMD reports 2020 52(1):3-10

Bibliography

PubMed
PMID 32154053
PubMed Central
PMC7052692
DOI
10.1002/jmd2.12092
Funding
Funding was not specified in the indexed record or accessible funding metadata.
Competing interests
Reported disclosure: B Schwahn reports personal fees from Orphan Europe, outside the submitted work. Other authors do not report any conflict of interest. T.S., H.S., P.V., A.D., J.F., H.J.B., J.F.B., B.A.B., J.J.B., and A.F. declare they have no conflict of interest.

Study snapshot

DesignCase-series safety review
ModelEvidence synthesis; mixed research models
Sample11 published and 4 additional CBS cases, plus 4 other encephalopathy cases
InterventionBetaine treatment in the setting of excess methionine
DurationVariable clinical follow-up
EndpointsHypermethioninemia; Brain edema; Monitoring

What the study showed, in plain terms

Published in 2020, this source examined prescription betaine and inherited metabolic disorders. Its evidence base was 11 published and 4 additional CBS cases, plus 4 other encephalopathy cases. It evaluated Betaine treatment in the setting of excess methionine across Variable clinical follow-up.

Severe methionine accumulation was associated with brain edema. Betaine can worsen methionine excess in CBS deficiency, making dietary control and monitoring essential.

Case-based evidence cannot estimate incidence; this rare-disease risk should neither be ignored nor generalized as a common effect in healthy adults.

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Key findings

  • Severe methionine accumulation was associated with brain edema.
  • Betaine can worsen methionine excess in CBS deficiency, making dietary control and monitoring essential.
  • The recorded outcome domains were Hypermethioninemia; Brain edema; Monitoring.

What this study can and cannot tell us

  • Case-based evidence cannot estimate incidence; this rare-disease risk should neither be ignored nor generalized as a common effect in healthy adults.
  • Case-based human safety evidence. A case series and narrative review cannot establish an incidence rate or a randomized treatment effect.
  • Source basis: Accessible full-text extract plus indexed bibliographic data. Missing method details, funding information or participant denominators are not inferred.

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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

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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