Homocystinuria
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGBetaine
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 10 weeks - at the end of follow-up of each patient | 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. |
Secondary
| Measure | Time frame |
|---|---|
| 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. | 10 weeks - at the end of follow-up of each patient |
| 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. | 10 weeks - at the end of follow-up of each patient |
Countries
France
Outcome results
None listed