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.
More than 300 mutations in the GALT gene have been identified in people with the classic form of galactosemia, a condition that causes life-threatening signs and symptoms beginning shortly after birth. 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) in galactose-1-phosphate uridylyltransferase. The most common GALT mutation in white Europeans and North Americans replaces the amino acid glutamine with the amino acid arginine at position 188 in the enzyme (written as Gln188Arg or Q188R). 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 or S135L).
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 or N314D). 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.
UDP Galactose Pyrophosphorylase