Betaine METABOLISM OF PATIENTS With Homocystinuria (HCTBETAINE)

Oral treatment with betaine is conventionally used for patients with inherited homocystinurias. These conditions include a first group of patients with a cystathionine β-synthase (CBS) deficiency and a second group of patients with remethylation defects. The aim of betaine therapy is to reduce level of total plasma homocysteine. Daily dosages and rhythm of administration proposed in the literature vary between 100 to 250 mg / kg / d in 2 to 4 doses. These dosages are not based on validated data and several publications mention much higher dosages particularly when total homocysteine is not controlled. These practices may be unnecessary or even detrimental given the fact that high doses of betaine could for example lead to secondary folate deficiency.

Oral treatment with betaine is conventionally used for patients with inherited homocystinurias. These conditions include a first group of patients with a cystathionine β-synthase (CBS) deficiency and a second group of patients with remethylation defects. The aim of betaine therapy is to reduce level of total plasma homocysteine. Daily dosages and rhythm of administration proposed in the literature vary between 100 to 250 mg / kg / d in 2 to 4 doses. These dosages are not based on validated data and several publications mention much higher dosages particularly when total homocysteine is not controlled. These practices may be unnecessary or even detrimental given the fact that high doses of betaine could for example lead to secondary folate deficiency.

Plasma level of total homocysteine upon oral treatment with Betaine at 100 mg / kg / day compared with 250 mg / kg / day in the same individual.

The assay technique used is MS/MS validated according to ISO standard 1589. Samples will be frozen and analysed at the end of follow-up of the study. Freezing does not affect the validity of the technique used.

Measurement of dimethylglycine plasma level following the loading dose of 100 mg / kg of betaine compared in the same person with the dose of 250 mg / kg.

Measurement of sarcosine plasma level following the loading dose of 100 mg / kg of betaine compared in the same person with the dose of 250 mg / kg.

Inclusion Criteria: ≥1 year and children <18 years, homocystinuria confirmed enzymatically or molecularly divided into 2 groups: CBS deficiency remethylation defects (CbIC defect and MTHFR deficiency) Diagnosis of homocystinuria since more than 1 year Continuous treatment of hyperhomocysteinemia in the last 12 months Exclusion Criteria: Deficits in cystathionine beta-synthase B6-responsive pregnancy breast-feeding Young pubescent girls not using effective contraception

Imbard A, Toumazi A, Magreault S, Garcia-Segarra N, Schlemmer D, Kaguelidou F, Perronneau I, Haignere J, de Baulny HO, Kuster A, Feillet F, Alberti C, Guilmin-Crepon S, Benoist JF, Schiff M. Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial. Orphanet J Rare Dis. 2022 Nov 14;17(1):417. doi: 10.1186/s13023-022-02567-4.