Little, Susan GLAUCOMA Galactosemia

July 5, 2011

Fact Sheet

Little, Susan – GLAUCOMA – Galactosemia

FACTS:

Definition –

ga·lac·to·se·mi·a

n.
An inherited metabolic disorder characterized by the deficiency of an enzyme that is necessary for the metabolism of galactose. The disorder results in elevated levels of galactose in the blood and, if untreated, can lead to mental retardation and eye and liver abnormalities.
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Basic Information about Galactosemia ~

• Galactosemia is a genetic condition that causes an inability to break down a sugar called galactose. Galactose is produced during the breakdown of lactose, which is the main sugar found in dairy products. Galactose is normally further broken down into smaller components that the body uses for energy.
• Patients with galactosemia cannot break down galactose, and as a result unhealthy levels of galactose may build up in the body. Because galactose is not properly metabolized, or broken down, galactosemia is classified as a metabolic disorder.
• Galactosemia is caused by a mutation, or error, in any of the three genes that provide instructions for making the enzymes that break down galactose. Galactosemia is inherited or passed down among family members as an autosomal recessive trait, meaning that an individual must inherit two copies of the mutated gene for the condition to develop. Mutations in several genes have been linked to galactosemia.
• Galactosemia affects about one in 30,000 to one in 60,000 newborns worldwide and appears to affect females and males equally. Signs of galactosemia may become apparent soon after birth. Infants with galactosemia may experience vomiting, liver failure, and bacterial infections. Severe bacterial infections may be fatal. Some infants with a milder form of galactosemia may develop cataracts or clouding of the lens of the eye.
• Liver problems may include enlargement and cirrhosis, in which scar tissue replaces healthy liver tissue. Some people with galactosemia may develop liver failure, which could be life-threatening if not recognized and treated appropriately.
• Currently there is no known cure for galactosemia. Treatment generally focuses on restricting dietary intake of lactose and galactose. If galactose levels are successfully controlled, most people with galactosemia can live normal lives.

Source: Natural Standard Research Collaboration (

What is Galactosemia?

Classic Galactosemia is a rare genetic metabolic disorder. The child with classic galactosemia inherits a gene for galactosemia from both parents, who are carriers. Patients who inherit the classic galactosemia gene from each parent are sometimes described as having the genetic makeup "G/G". Normally when a person consumes a product that contains lactose (e.g., dairy products such as milk, cheese, butter), the body breaks the lactose down into galactose and glucose. Glucose is the sugar used by the body for energy. Galactosemia means too much galactose in the blood caused by the individual "missing" the enzyme (known as GALT) to convert galactose into glucose. This accumulation of galactose is a poison to the body and can cause serious complications such as the following and if untreated, as high as 75% of infants will die:

• an enlarged liver
• kidney failure
• cataract
• brain damage

Diagnosis is made usually within the first week of life by blood test from a heel prick as part of a standard newborn screening. Treatment requires the strict exclusion of lactose/galactose from the diet. Although galactosemic children are started on diet restriction at birth, there continues to be a high incidence of long-term complications involving speech and language, fine and gross motor skill delays and specific learning disabilities. Ovarian failure may occur in girls. Prenatal diagnosis by amniocentresis is also available.

History

Galactosemia was first "discovered" in 1908. Von Ruess, in a 1908 publication entitled, "Sugar Excretion in Infancy," reported on a breast-fed infant with failure to thrive, enlargement of the liver and spleen, and "galactosuria". This infant ceased to excrete galactose through the urine when milk products were removed from the diet. The infant, however, later died because of other complications (the baby had been given tea laced with cognac as treatment as well). An autopsy revealed cirrhosis of the liver, which they thought was due to the infant's alcohol ingestion. Though confirmation of the diagnosis was not possible at that time, it has been generally accepted that Von Ruess was the first to report on a patient with galactosemia.

By 1917, "galactosuria" was a broadly recognized inherited disorder and was treated by removal of milk products from the diet.

The disease was first recognized and described in detail (ie published work) in 1935 by Mason and Turner. Leloir worked out the metabolic pathway and the process of sugar-nucleotides and won the Nobel prize in Chemistry in 1970 for his work. He and coworkers elucidated the pathway for converting galactose to glucose in the early 50's.

Although, the clinicians recognized galactosemia very early in the century, the defective gene that caused it wasn't found until 1956. Another major break-through was when it was first found to be detectable through a newborn screening method in 1963. This method was developed by Guthrie and Paigen. Galactosemia was the second disorder found to be detectable through newborn screening methods by Robert Guthrie.

Source :Parents of Galactosemic Children, Inc. (PGC)

How common is galactosemia?

Classic galactosemia occurs in 1 in 30,000 to 60,000 newborns. Galactosemia type II and type III are less common; type II probably affects fewer than 1 in 100,000 newborns and type III appears to be very rare.

What genes are related to galactosemia?

Mutations in the GALE, GALK1, and GALT genes cause galactosemia.

The GALE, GALK1, and GALT genes provide instructions for making enzymes that are essential for processing galactose obtained from the diet. These enzymes break down galactose into another simple sugar, glucose, and other molecules that the body can store or use for energy.

Mutations in the GALT gene are responsible for classic galactosemia (type I). Most of these genetic changes almost completely eliminate the activity of the enzyme produced from the GALT gene, preventing the normal processing of galactose and resulting in the life-threatening signs and symptoms of this disorder. Another GALT gene mutation, known as the Duarte variant, reduces but does not eliminate the activity of the enzyme. People with the Duarte variant tend to have much milder features of galactosemia.

Galactosemia type II results from mutations in the GALK1 gene, while mutations in the GALE gene underlie galactosemia type III. Like the enzyme produced from the GALT gene, the enzymes made from the GALK1 and GALE genes play important roles in processing galactose. A shortage of any of these critical enzymes allows galactose and related compounds to build up to toxic levels in the body. The accumulation of these substances damages tissues and organs, leading to the characteristic features of galactosemia.

How do people inherit galactosemia?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Source: Genetics Home Reference

More information on genetics of Galactosemia.

Galactosemia is passed on from parents to their child. Technically it is called an autosomal recessive trait, which means that both of the parents of the child with galactosemia are carriers of the disorder. The carriers of the disorder will not get sick. But when two carriers have a child together there is a 1 in 4 chance (25%) the child will have galactosemia, a 2 in 4 chance (50%) the child will be a carrier of the disease, and a 1 in 4 chance (25%) the child will not be a carrier or have the disease. These are the chances with each birth.

If one child in a family is diagnosed with Galactosemia then all children born before and/or after should also be tested. Each new baby in the family should be started on a galactose-and lactose free formula even before the enzyme test results are back. If you had planned to breast-feed your baby, pump your breast milk until the test results come back. If the new baby does not have galactosemia, the baby can be breast-fed or changed to a milk-based infant formula.

During pregnancy an amniocentesis test may detect if the infant has Galactosemia.

What Galactosemia may look like:

Clinical Symptoms

Although infants with galactosemia may appear normal at birth, within a few days to two weeks after initiating milk feedings, the symptoms of untreated galactosemia can become very severe. Early signs of the disease include feeding problems, poor sucking reflex, jaundice and hepatomegaly. Other symptoms may include failure to thrive, lethargy, cataracts, hypoglycemia, coagulation problems and decreased immunity.

What problems can Galactosemia cause?

Studies show that over the years children and young adults with galactosemia can have problems with speech, language, hearing, fine-motor coordination, hemorrhage of the gel-like substance of the eye, tremors, stunted growth, and certain learning disabilities. Galactosemia is different for each child and will not cause the same problems with all children. Even when all instructions are followed, some children do not do as well as others. Studies tell us that children who were not given the strict diet have an increased risk of having one or more of the problems listed above.

For most girls with galactosemia, a problem called ovarian failure can happen. Ovarian failure means that the ovaries (where the eggs for having babies come from) either do not develop before she is born or they won't work as she grows up. Again, because it is different for each girl, the best way to deal with this problem is to talk with her doctor to find out the latest information.

Treatment

A very strict diet is essential. With a restricted diet the child with galactosemia may have less severe symptoms. There is no chemical or drug substitute that can be taken for the missing enzyme. The treatment for galactosemia is to restrict galactose and lactose from the diet for life. This means that foods that have galactose and lactose must be avoided. Since galactose is a part of lactose, or milk sugar, all milk and all foods that have milk in them must not be eaten. This is not just cow's milk, but any animal's milk including goat's milk and human breast milk. This includes dairy products like butter, cheese, and yogurt. Other foods that have small amounts of milk products in other forms

such as whey, casein, and curds must also be eliminated. Also some foods known as "organ meats" such as brain, liver, thymus and pancreas (sometimes called sweetbreads) should not be eaten because they contain stored galactose.

Source: Texas Department of State Health Services