Using D-Galactose as a food supplement in Congenital Disorders of Glycosylation (CDG)

Congenital Disorders of Glycosylation (CDG) is a recently discovered metabolic
disorder that changes the way sugars are broken down and disrupts how these
sugars are built in a person*s body1. Congenital Disorders of Glycosylation
(CDG) leads to severe metabolic alterations in patients. These include
hypoglycemia (low blood sugar levels), abnormal liver function, abnormal
hormone levels, and muscle symptoms2,3,4. The symptoms occur due to changes in
the normal structure and attachment of the sugar chains that are built on the
surface of body proteins and will stay attached to the proteins in a healthy
individuals body5,6,7. The development of effective dietary interventions for
Congenital Disorders of Glycosylation is limited because of our poor
understanding of the disease. Galactose, the simple milk sugar has been applied
as a dietary supplement, and in high dosage (50g/dose) has been used in
clinical loading tests for more then 50 years, without side effects. Increased
intake of galactose, has previously shown beneficial effects on the sugar chain
structure on body proteins (this is called glycosylation) initially in 6
patients with PGM1 deficiency8. The positive effect of galactose was proven in
cell culture studies of patients as well8. Since then patients with other types
of CDGs have been trialed on galactose supplements with succes

The goal of this study is to better characterize the metabolic alterations and
sugar structure alterations (glycosylation abnormalities) in patients diagnosed
with Congenital Disorders of Glycosylation.

Over a two-year period, we will enroll patients diagnosed with Congenital
Disorders of Glycosylation. We propose to administer oral galactose
supplementation for a period of 18 weeks in increasing dose to assess its
effectiveness at normalizing glycosylation. Galactose will be given in a series
of doses within the range of normal dietary intake of galactose over fixed time
points. To assess the effects of oral galactose supplementation for each
participant, changes in participant growth, as well as blood sugar levels,
coagulation parameters and liver function (the primary clinical features of
Congenital Disorders of Glycosylation) will be correlated with biomarkers
derived from participant blood and urine samples obtained at key time points
and then compared to standard normative ranges of data for each measure.

1The participant will remain on his/her regular diet and will be asked to
ingest an oral galactose (simple milk sugar) supplement. The amount of
galactose in the supplement will be not more than what is found in a
recommended healthy diet. The maximum galactose dose used is 50g/day. This
dosage has been shown to be safe when used in healthy individuals in oral or
venous administration, and when taken by mouth for several weeks9,10,13,14.

This oral supplement, *D-Galactose*, is a simple tasteless powder measured by
spoon (Necaseo) and will be taken by mouth. The galactose dosage will be
increased in three increments as follows throughout the 18 weeks of the study
period: 0.5 g galactose per kg (first 6 weeks), 1.0 g per kg (weeks 7-12), and
1.5 g per kg (weeks 13-18) (maximum daily dose : 50g).

At this moment there is no treatment for patients with CDG. All patients with
CDG have a (severe) cognitive imairment. Burden and risks are acceptable in our
opinion in relation to the progeressive charcater of the CDG. A recently
published pilot study shows that galactose is safe and tolerated in CDG1A
patients. (Marova et al., 2017)