Cystathionine beta synthase deficiency and brain edema associated with methionine excess under betaine supplementation: Four new cases and a review of the evidence.

ABSTRACT: CBS deficient individuals undergoing betaine supplementation without sufficient dietary methionine restriction can develop severe hypermethioninemia and brain edema. Brain edema has also been observed in individuals with severe hypermethioninemia without concomitant betaine supplementation. We systematically evaluated reports from 11 published and 4 unpublished patients with CBS deficiency and from additional four cases of encephalopathy in association with elevated methionine. We conclude that, while betaine supplementation does greatly exacerbate methionine accumulation, the primary agent causing brain edema is methionine rather than betaine. Clinical signs of increased intracranial pressure have not been seen in patients with plasma methionine levels below 559??mol/L but occurred in one patient whose levels did not knowingly exceed 972??mol/L at the time of manifestation. While levels below 500??mol/L can be deemed safe it appears that brain edema can develop with plasma methionine levels close to 1000??mol/L. Patients with CBS deficiency on betaine supplementation need to be regularly monitored for concordance with their dietary plan and for plasma methionine concentrations. Recurrent methionine levels above 500??mol/L should alert clinicians to check for clinical signs and symptoms of brain edema and review dietary methionine intake. Levels approaching 1000??mol/L do increase the risk of complications and levels exceeding 1000??mol/L, despite best dietetic efforts, should be acutely addressed by reducing the prescribed betaine dose.

SUBMITTER: Schwahn BC 

PROVIDER: S-EPMC7052692 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature