#galactosaemia

Galactosaemia describes the presence of galactose in the blood. Galactose is a sugar which mainly comes from lactose, the sugar found in milks. Lactose is normally broken down into the two simple sugars, galactose and glucose. The galactose is then broken down further and used in many parts of the body including the brain. 

Galactosaemia is an autosomal recessive deficiency in enzyme (galactose-1-phosphate uridyltransferase) responsible for galactose metabolism

Causes build up of galactose in tissues

Symptoms:

Pathogeneseis:

Galactose-1-phosphate uridyltransferase converts Galactose-1-phosphate and UDPglucose to UDPgalactose and Glucose-1-phosphate. This can continue down the normal galactose metabolism pathway. 

Galactosaemia = deficiency in galactose-1-phosphate uridyltransferase. Galactose-1-phosphate accumulates. 

G1P is extremely toxic.

Accumulation of G1P means polyol pathway of carbohydrate metabolism takes place. 

Aldose reductase reduces galactose to sugar alcohol galactitol.

Galactitol is not suitable substrate for next enzyme in the pathway; polyol dehydrogenase. 

Galactitol accumulates (excreted in urine). 

Galactitol is responsible for many negative effects. E.g. osmotic effects - causes lens swelling and hence cataracts.

Accumulated galactose can also be oxidated to galactonate. 

Galactonate can be used in the pentose phosphate pathway, so is less harmful. 

Other types:

UDP-galactose to UDP-glucose catalysed by UDP-galactose-4 epimerase. Lack of this enzyme is Type 3. 

Galactose to Galactose-1-phosphate catalysed by galactokinase. Lack of galactokinase is type 2. 

If untreated, macrovesicular steatosis is commonly reported, with evolution to fibrosis and cirrhosis, instead of glycogen accumulation. In more recent studies, young rats fed with galactose exhibit similar histopathological modification in the liver and suggest that oxidative stress has an important role in liver dysfunction.

G is for Galactosaemia

People with galactosaemia are unable to metabolise galactose (a type of sugar) due to the lack of certain enzymes.

Below is the metabolic pathway for galactose

In galactosaemia, patients can’t utilise galactose because they lack kinase enzyme or the transferase enzyme. Cases where the transferase enzyme is absent are more common and much more serious than cases where the galactokinase enzyme is absent. This is because when the kinase enzyme is absent, only galactose accumulates in tissues. When the transferase enzyme is absent, galactose 1-phosphate as well as galactose accumulates in tissues.

When galactose accumulates in tissues, it is reduced to galactitol and this uses up NADPH. This can lead to the formation of cataracts. In addition, if galactose and galactitol accumulate, it can also lead to glaucoma.  Accumulation of galactose 1-phosphate can lead to damage of many organs e.g. liver, kidney and brain. Jaundice and hepatomegaly can develop and there is normally a reluctance to feed within the first few weeks of life. They can also suffer from developmental delay.