Galactosaemia is an inherited condition caused by a lack of an enzyme (catalyst) which normally breaks down galactose (the sugar found in milk products). This affects 1:19,000 births annually in Ireland (the highest incidence worldwide) and is screened for by the National Newborn Screening Programme. When an affected infant is diagnosed, galactose is immediately restricted from the diet. This prevents often fatal liver disease and other immediate complications. However, despite early treatment the majority of affected patients go on to develop long-term complications such as intellectual impairment, neurological complications, speech difficulties and infertility in females. The underlying mechanisms for these complications are unclear. The investigators have shown in detailed biochemical and gene analysis studies that major abnormalities affecting the function of complex molecules in the body, particularly glycoproteins, (consisting of sugar chains attached to proteins) persist in treated individuals which may lead to disturbances of the body's intrinsic cellular machinery and relate to the complications seen. In this research the investigators expand on from their earlier studies to see if they can identify biomarkers and parts of the galactose/glycosylation pathways which could be modified or changed with new treatments to improve outcomes for this condition (i.e., IgG N glycans). In more detail, the investigators test the use of the most abundant glycoprotein in human plasma (IgG) as an improved clinical test for monitoring the galactose control needed in patients and also to see if some patients (including children aged 5-12 yrs) might have a better predicted outcome with moderate increases of galactose in the diet. The investigators believe that these studies greatly improve the understanding of Galactosaemia with a view to improving current treatment options and future outcomes.

NCT02218632

Conditions

1. Classical Galactosaemia

Interventions

1. Other: lactose-free diet
2. Dietary Supplement: Temporary oral galactose supplements

MeSH:Galactosemias

HPO:Galactose intolerance Hypergalactosemia

Inclusion Criteria: - Classical galactosaemia - Q188R Genotype - On lactose-free diet - No complications, condition well controlled - Male/femal adults and children aged between 5-12 yrs. --- Q188R ---

- Informed consent /assent - Patient attend the Galactosaemia Clinic, NCIMD Dublin Exclusion Criteria: - Complications, such as cataracts - Galactosaemia varaint, no Q188R-Genotype - Poor compliance - Intercurrent illness - Individual may not complete follow up - Children below 5 years of age - Unable to provide informed consent - Patient not under the care of Galactosaemia Clinic, NCIMD Dublin Inclusion Criteria: - Classical galactosaemia - Q188R Genotype - On lactose-free diet - No complications, condition well controlled - Male/femal adults and children aged between 5-12 yrs. --- Q188R ---

- Informed consent /assent - Patient attend the Galactosaemia Clinic, NCIMD Dublin Exclusion Criteria: - Complications, such as cataracts - Galactosaemia varaint, no Q188R-Genotype - Poor compliance - Intercurrent illness - Individual may not complete follow up - Children below 5 years of age - Unable to provide informed consent - Patient not under the care of Galactosaemia Clinic, NCIMD Dublin Inclusion Criteria: - Classical galactosaemia - Q188R Genotype - On lactose-free diet - No complications, condition well controlled - Male/femal adults and children aged between 5-12 yrs. --- Q188R --- --- Q188R ---

- Informed consent /assent - Patient attend the Galactosaemia Clinic, NCIMD Dublin Exclusion Criteria: - Complications, such as cataracts - Galactosaemia varaint, no Q188R-Genotype - Poor compliance - Intercurrent illness - Individual may not complete follow up - Children below 5 years of age - Unable to provide informed consent - Patient not under the care of Galactosaemia Clinic, NCIMD Dublin Classical Galactosaemia Galactosemias Classical Galactosaemia is an inherited disorder of galactose metabolism caused by profound deficiency of galactose-1-phosphate uridyltransferase (GALT: EC 2.7.712). --- Q188R ---

The majority of Irish patients harbour the severe Q188R Galt mutation. --- Q188R ---