Dedicated to our galactosemic children

The Genetics Of It All

All types of galactosemia are inherited in an autosomal recessive manner (see diagram).  This means that a person has to inherit a gene change from each parent for the condition to manifest.  For Duarte galactosemia, a child must inherit one gene with a classical galactosemia mutation (G) and one gene with a Duarte mutation (D).  The table below shows the possibilities for a child when one parent is a carrier for classical galactosemia and the
other parent is a carrier for Duarte galactosemia.

 

 

Duarte (D)

Normal (N)

Galactosemia (G)

D/G

N/G

Normal (N)

D/N

N/N

N/N = Two normal alleles (100% enzyme activity)
N/G = Carrier of classical galactosemia (50% enzyme activity)
D/N = carrier of Duarte galactosemia (about 75% enzyme activity)
D/G = Duarte galactosemia (about 25 - 50% enzyme activity)

 

 

 

 

 

 

 

 

 

 

 

 

A couple who has one child with Duarte galactosemia has a 25% chance of having another child with Duarte galactosemia in each subsequent pregnancy. The dietary treatment of children with Duarte galactosemia is more flexible than in children with classical galactosemia.

(State of Missouri Dept of Health)

 

What is the normal function of the GALT gene?

The GALT gene provides instructions for making an enzyme called galactose-1-phosphate uridylyltransferase. This enzyme enables the body to process a simple sugar called galactose, which is present in small amounts in many foods. Galactose is primarily part of a larger sugar called lactose, which is found in all dairy products and many baby formulas.

Galactose-1-phosphate uridylyltransferase is responsible for one step in a chemical process that breaks down galactose into other molecules that can be used by the body. Specifically, this enzyme converts a modified form of galactose (galactose-1-phosphate) to glucose, which is another simple sugar. Glucose is the main energy source for most cells. This chemical reaction also produces another form of galactose (UDP-galactose) that is used to build galactose-containing proteins and fats. These modified proteins and fats play critical roles in chemical signaling, building cellular structures, transporting molecules, and producing energy.

How are changes in the GALT gene related to health conditions?

galactosemia - caused by mutations in the GALT gene

More than 180 mutations in the GALT gene have been identified in people with the classic form of galactosemia. Most of these mutations severely reduce or eliminate the activity of galactose-1-phosphate uridylyltransferase. A shortage of this enzyme prevents cells from processing galactose obtained from the diet. As a result, galactose-1-phosphate and related compounds can build up to toxic levels in the body. The accumulation of these substances damages tissues and organs, leading to the serious medical problems associated with classic galactosemia.

Most changes in the GALT gene alter single protein building blocks (amino acids) used to build galactose-1-phosphate uridylyltransferase. The most common GALT mutation in Caucasian (white) Europeans and North Americans replaces the amino acid glutamine with the amino acid arginine at position 188 in the enzyme (written as Gln188Arg). Another mutation occurs almost exclusively in people of African descent. This genetic change substitutes the amino acid leucine for the amino acid serine at position 135 (written as Ser135Leu).

A particular GALT mutation called the Duarte variant results in a form of galactosemia with less serious complications than the classic type. This mutation replaces the amino acid asparagine with the amino acid aspartic acid at protein position 314 (written as Asn314Asp). The Duarte variant reduces but does not eliminate the activity of galactose-1-phosphate uridylyltransferase. The signs and symptoms associated with this variant tend to be milder because the enzyme retains 5 percent to 20 percent of its normal activity.