Galactosemia Health Article

Definition

Galactosemia is an inherited disease in which the transformation of galactose to glucose is blocked, allowing galactose to increase to toxic levels in the body. If galactosemia is untreated, high levels of galactose cause vomiting, diarrhea, lethargy, low blood sugar, brain damage, jaundice, liver enlargement, cataracts, susceptibility to infection, and death.

Description

Galactosemia is a rare but potentially life-threatening disease that results from the inability to metabolize galactose. Serious consequences from galactosemia can be prevented by screening newborns at birth with a simple blood test.

Galactosemia is an inborn error of metabolism. "Metabolism" refers to all chemical reactions that take place in living organisms. A metabolic pathway is a series of reactions where the product of each step in the series is the starting material for the next step. Enzymes are the chemicals that help the reactions occur. Their ability to function depends on their structure, and their structure is determined by the deoxyribonucleic acid (DNA) sequence of the genes that encode them. Inborn errors of metabolism are caused by mutations in these genes which do not allow the enzymes to function properly.

Sugars are sometimes called "the energy molecules," and galactose and glucose are both sugars. For galactose to be utilized for energy, it must be transformed into something that can enter the metabolic pathway that converts glucose into energy (plus water and carbon dioxide). This is important for infants because they typically get most of their nutrient energy from milk, which contains a high level of galactose. Each molecule of lactose, the major sugar constituent of milk, is made up of a molecule of galactose and a molecule of glucose, and so galactose makes up 20% of the energy source of a typical infant's diet.

Three enzymes are required to convert galactose into glucose-1-phosphate (a phosphorylated glucose that can enter the metabolic pathway that turns glucose into energy). Each of these three enzymes is encoded by a separate gene. If any of these enzymes fail to function, galactose build-up and galactosemia result. Thus, there are three types of galactosemia with a different gene responsible for each.

Every cell in a person's body has two copies of each gene. Each of the forms of galactosemia is inherited as a recessive trait, which means that galactosemia is only present in individuals with two mutated copies of one of the three genes. This also means that carriers, with only one copy of a gene mutation, will not be aware that they are carrying a mutation (unless they have had a genetic test), as it is masked by the normal gene they also carry and they have no symptoms of the disease. For each step in the conversion of galactose to glucose, if only one of the two copies of the gene controlling that step is normal (i.e. for carriers), enough functional enzyme is made so that the pathway is not blocked at that step. If a person has galactosemia, both copies of the gene coding for one of the enzymes required to convert glucose to galactose are defective and the pathway becomes blocked. If two carriers of the same defective gene have children, the chance of any of their children getting galactosemia (the chance of a child getting two copies of the defective gene) is 25% (one in four) for each pregnancy.

Classic galactosemia occurs in the United States about one in every 50,000–70,000 live births.

Galactosemia I

Galactosemia I (also called classic galactosemia), the first form to be discovered, is caused by defects in both copies of the gene that codes for an enzyme called galactose-1-phosphate uridyl transferase (GALT). There are 30 known different mutations in this gene that cause GALT to malfunction.

Newborns with galactosemia I appear normal at birth, but begin to develop symptoms after they are given milk for the first time. Symptoms include vomiting, diarrhea, lethargy (sluggishness or fatigue), low blood glucose, jaundice (a yellowing of the skin and eyes), enlarged liver, protein and amino acids in the urine, and susceptibility to infection, especially from gram negative bacteria. Cataracts (a grayish white film on the eye lens) can appear within a few days after birth. People with galactosemia frequently have symptoms as they grow older even though they have been given a galactose-free diet. These symptoms include speech disorders, cataracts, ovarian atrophy and infertility in females, learning disabilities, and behavioral problems.

Galactosemia II

Galactosemia II is caused by defects in both copies of the gene that codes for an enzyme called galactokinase (GALK). The frequency of occurrence of galactosemia II is about one in 100,000–155,000 births.

Galactosemia II is less harmful than galactosemia I. Babies born with galactosemia II will develop cataracts at an early age unless they are given a galactose-free diet. They do not generally suffer from liver damage or neurologic disturbances.