Residual galactose oxidation capacity and galactosylation abnormalities as possible predictors for galactose tolerance and outcome in patients with galactose-1-phosphate uridyltransferase deficiency

Residual galactose oxidation capacity and galactosylation abnormalities as possible predictors for galactose tolerance and outcome in patients with galactose-1-phosphate uridyltransferase deficiency - Galactose oxidation and galactosylation in Classical Galactosemia

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON46279

Enrollment

Registered

2018-01-09

Start date

2017-09-14

Completion date

Unknown

Last updated

2024-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Classical galactosemia galactose-1-phosphate uridyltransferase deficiency

Interventions

fibroblast

galactosylation

oxidation

Part B1: In vivo galactose oxidation measurement (galactose breath test) The subject is not allowed to eat or drink 2 hours before the test. Drinking water is allowed during the test. Adults will be

classical galactosemia

Eligibility

Age

2 Years to 64 Years

Inclusion criteria

Inclusion criteria: GALT enzyme activity

Exclusion criteria

Exclusion criteria: individuals with swallowing difficulties will be excluded from part B1 (galactose breath test) of the study

Design outcomes

Primary

Measure	Time frame
Main study parameters/endpoints: Part A: Galactosylation patterns In serum G0 (agalactosylated)/G1 (monogalactosylated) and G0/G2 (digalactosylated) incorporation ratios which signal N glycan processing defects will be determined. The association of these incorporation ratios with phenotype of CG (mild or severe) will be assessed. Part B1: In vivo galactose oxidation capacity The cumulative percentage of ingested [1-13C galactose] retrieved as [1-13C] CO2 in expired air (CUMPD), will be measured in breath samples taken at baseline and at 60, 90 and 120 minutes after a dose of 7 mg/kg [1-13C] galactose. The association of these cumulative retrieved proportions with phenotype of CG (mild or severe) will be assessed. Part B2: In vitro galactose oxidation capacity The galactose index (ratio of U13C6-Galactose-1-phosphate/ U13C6-UDP-Galactose) which is a measure for galactose metabolism, will be measured in fibroblasts after two hours of incubation with U13C6-galactose.The association of this galactose index with phenotype of CG (mild or severe) will be assessed. Group means will be compared, we will perform logistic regression analysis to quantify the association between determinants and phenotype subgroup. Receiver Operator Characteristics (ROC) curves will be made, and the Area Under the Curve (AUC) will be calculated to determine the usefulness of the determinants as diagnostic indicators for severe phenotype.	—

Measure

Time frame

Main study parameters/endpoints: Part A: Galactosylation patterns In serum G0 (agalactosylated)/G1 (monogalactosylated) and G0/G2 (digalactosylated) incorporation ratios which signal N glycan processing defects will be determined. The association of these incorporation ratios with phenotype of CG (mild or severe) will be assessed. Part B1: In vivo galactose oxidation capacity The cumulative percentage of ingested [1-13C galactose] retrieved as [1-13C] CO2 in expired air (CUMPD), will be measured in breath samples taken at baseline and at 60, 90 and 120 minutes after a dose of 7 mg/kg [1-13C] galactose. The association of these cumulative retrieved proportions with phenotype of CG (mild or severe) will be assessed. Part B2: In vitro galactose oxidation capacity The galactose index (ratio of U13C6-Galactose-1-phosphate/ U13C6-UDP-Galactose) which is a measure for galactose metabolism, will be measured in fibroblasts after two hours of incubation with U13C6-galactose.The association of this galactose index with phenotype of CG (mild or severe) will be assessed. Group means will be compared, we will perform logistic regression analysis to quantify the association between determinants and phenotype subgroup. Receiver Operator Characteristics (ROC) curves will be made, and the Area Under the Curve (AUC) will be calculated to determine the usefulness of the determinants as diagnostic indicators for severe phenotype.

—

Countries

The Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)