Newborn screening for Classic Galactosemia involves a dried blood spot test, where a sample of blood is taken from the heel. The blood is tested for GALT enzyme activity and total levels of galactose. If GALT enzyme activity is very low or completely undetected, or if there are high levels of galactose, the patient may have Classic Galactosemia. A Genetic test will be performed to confirm the diagnosis.
Newborn
- Liver failure
- Kidney problems
- Sepsis
- Brain edema
- Pseudotumor cerebri
- Feeding difficulties
- Growth problems
- Cataracts
Infants/Toddlers
- Speech/ language delays
- Coordination problems (fine and gross motor skills)
- Developmental delays
- Attention issues
- Growth problems
- Cataracts
Young Children
- Learning delays
- Issues with fine and gross motor skills (e.g., handwriting)
- Growth problems
- Speech/ language problems
- Behavioral and emotional issues
- Tremor
Teen
- Puberty and fertility problems (females)
- Growth delays
- Anxiety
- Social problems
- Learning difficulties
- Tremor
Adult
- Tremor
- Seizures
- Anxiety
- Depression
- Attention Deficit Hyperactivity Disorder (ADHD)
- Cataracts
There are two subtypes of Galactosemia – Classic Galactosemia and GALK Deficiency. Each of these types is caused by a different enzyme not working properly or missing in some amounts in the body. In healthy individuals, these enzymes are involved in breaking down galactose.
Classic Galactosemia and GALK Deficiency can greatly affect children’s development potential and quality of life, and may cause motor, speech and cognitive deficiencies, cataracts, tremors, seizures and (in females) primary ovarian insufficiency.
Classic Galactosemia is the most common subtype of the disorder. Patients with Classic Galactosemia have mutations or deletions in both copies (one from each parent) of their GALT genes, which means that the GALT enzyme is completely inactive. Patients with GALK Deficiency have mutations or deletions in the gene that codes for the GALK enzyme. GALT and GALK enzymes are necessary to process galactose. Without a place to go, excess galactose builds up. The enzyme Aldose Reductase, not normally involved in galactose metabolism, is activated to convert galactose into galactitol, an abnormal and toxic substance that is believed to cause the acute and long-term complications of Galactosemia. Galactitol is not produced or found in individuals who do not have Galactosemia.
Galactosemia is a problem processing galactose, a kind of sugar found in dairy products such as milk, cheese, butter, and other foods.
To understand why this happens, we need to look at metabolic pathways. These are chemical reactions that convert molecules into the body. When everything in the body is working the way it should, galactose is converted into a specific pathway (pathway 1). In this pathway, galactose is converted into a metabolite called Gal-1p. People with Galactosemia are missing an enzyme called GALT, so Gal-1p cannot be processed any further. Instead, Gal-1p is backed up and clogs the pathway, meaning galactose cannot go where it should go. When this happens, galactose overflows into a different pathway (pathway 2) where it should not go.
When galactose travels down pathway 2, it does not know how to properly process the galactose. An enzyme that is not supposed to be involved called Aldose Reductase steps in and converts the galactose. Aldose Reductase changes galactose into toxic galactitol causing harm to the body. Galactitol can cause build up in the blood, tissues and organs including the brain. Finding new ways to block toxic galactitol may help reduce damage to the body.