Monosodium Glutamate Supplementation IN GLutaminaSe Deficiency
Research type
Research Study
Full title
Investigating the safety, tolerability and effectiveness of dietary monosodium glutamate supplementation in patients with glutaminase deficiency.
IRAS ID
264159
Contact name
Saikat Santra
Contact email
Sponsor organisation
Birmingham Women's and Children's NHS FT
Duration of Study in the UK
2 years, 0 months, 2 days
Research summary
Glutaminase deficiency (GD) is a newly described inherited metabolic disorder (IMD) due to abnormalities in the GLS gene. Glutaminase breaks down glutamine to glutamate so GD would be predicted to cause high glutamine levels and low glutamate levels. The five reported patients have all been somewhat different but developmental delay and difficulties with walking (such as ataxia) are consistent features of the disorder. Patients do have elevated levels of glutamine in the blood. This is usually seen in children with high ammonia levels but GD patients have normal ammonia levels. In our experience glutamine-lowering medicines (such as sodium phenylbutyrate) have not reduced the glutamine level nor led to any clinical benefit.
Patients have not been found to have low levels of glutamate in the blood or the fluid around the brain (CSF) but skin cells from affected patients have been shown to have low levels of glutamate inside them. If this intracellular glutamate deficiency is why GD patients develop problems, they might benefit from supplementing glutamate in the diet. A zebrafish model of GD demonstrated some improvement in the way affected embryos develop with glutamate supplementation.
We would like to test this by assessing the safety and clinical effect of supplementing the diet of GD patients with the widely available food ingredient monosodium glutamate (MSG). REC approval is being sought for this protocol although treatment would be monitored through existing clinical care arrangements. Patients would be seen in IMD clinics more frequently than usual, have blood extra tests to monitor the safety of the change in diet and have formal assessments of the nervous system and walking to see if there is a clinical change on treatment. Only two children are known to be diagnosed in the UK with this disorder and both will be recruited to this study.
REC name
West Midlands - Black Country Research Ethics Committee
REC reference
20/WM/0067
Date of REC Opinion
10 Jun 2020
REC opinion
Further Information Favourable Opinion