Galactosemia is a rare, hereditary disorder of carbohydrate metabolism that affects the body's ability to convert galactose (a sugar contained in milk, including human mother's milk) to glucose (a different type of sugar). Galactose is converted to glucose by a series of three enzyme reactions. The disorder is caused by a deficiency of an enzyme known as "galactose-1-phosphate uridyl transferase" which is vital to this process.
Galactosemia may also be referred to as classic galactosemia because a few variants of the gene for galactosemia have been identified. One variant causes a milder form of the disorder known as Duarte galactosemia. Classic galactosemia is the most severe form.
Because milk is the staple of an infant's diet, early diagnosis and treatment of this disorder is absolutely essential to avoid serious lifelong disability.
An infant with galactosemia appears normal at birth, but within a few days or weeks loses his appetite (anorexia) and starts vomiting excessively. Yellowing of the skin, mucous membranes, and whites of the eyes (jaundice), enlargement of the liver (hepatomegaly), appearance of amino acids and protein in the urine, growth failure, and, ultimately, accumulation of fluid in the abdominal cavity (ascites) and other swelling (edema) may also occur. Diarrhea, irritability, lethargy and repeated bacterial infections may also be early signs of galactosemia. In time, wasting of body tissues, marked weakness, and extreme weight loss occur unless the infant is treated for the deficiency.
Children with galactosemia who have not received early treatment may show arrested physical and mental development and are particularly susceptible to cataracts in infancy or childhood. In severe cases, overwhelming infection can cause life-threatening complications, but mild cases present few symptoms and no serious impairment(s).
In order to avoid the consequences of galactosemia, which may include liver or kidney failure, brain damage and/or cataracts, infants must be treated promptly by removing galactose totally from the diet. Children treated with this special diet usually show satisfactory general health and growth. They can make reasonable, though often not optimal, intellectual progress. Speech and vision difficulties and some behavioral problems may occur. Ovarian impairment is not uncommon in girls with galactosemia because of an increase in the blood level of the hormone gonadotropin; males with galactosemia have also been identified who have an excessive level of gonadotropin (hypergonadotropinism).
The abovementioned complications associated with classic galactosemia have not occurred in individuals with Duarte galactosemia. Significant debate exists in the medical literature as to whether individuals with Duarte galactosemia need to maintain a special diet.
Galactosemia is an autosomal recessive hereditary disorder. The most severe form of the disorder is caused by a deficiency of the enzyme galactose-1- phosphate uridyl transferase. The milder form is caused by a deficiency of the enzyme galactokinase. These enzymes are needed for the breakdown of the milk sugar, galactose. Two different toxic products in galactosemic patients have been identified: galactitol (an alcoholic derivative of galactose) and galactose-1-phosphate (a salt of galactose). Galactitol accumulates in the lens of the eye where it causes lens swelling and protein precipitation and, subsequently, cataracts. Accumulations of galactose-1-phosphate cause the other symptoms.
Genetic diseases are determined by two genes, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.
Investigators have determined that galactosemia occurs due to disruptions or changes (mutations) of the GALT gene located on the short arm of chromosome 9 (9p13). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 9p13″ refers to band 13 on the short arm of chromosome 9. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
The abnormal accumulation of galactose in various organs of the body causes the symptoms and physical findings of galactosemia.
Galactosemia appears in about 1 in 35-60,000 live births, with as many males affected as females. The disorder has been reported in all ethnic groups. An increased frequency of galactosemia occurs in individuals of northern European ancestry.
Pregnant women who are carriers for galactosemia (without symptoms) can be detected by testing for the activity of the enzyme “galactose-1-phosphate uridyl transferase” in their red blood cells. If the enzyme activity is 50% of the normal value, the individual is a carrier.
Infants at risk for galactosemia can and should be diagnosed at birth (or earlier) by testing for enzyme activity levels in red blood cells, using a drop of blood from the umbilical cord.
Children with galactosemia should have a diet that contains lactose-free milk substitutes and other foods such as casein hydrolysates and soy bean products. Strict dietary restriction should be maintained until the child is at least 2 years old or preferably 6 years. A lactose tolerance test should NOT be administered to galactosemic children. Fortunately the body of an infant with galactosemia can synthesize galactolipids and other essential galactose-containing compounds without the presence of galactose in food. Therefore, satisfactory physical development is possible if a strict diet is followed.
Appropriate treatment (i.e., antibiotic drugs) may be necessary to control infection. The emotional effects of the strict diet may require attention and supportive measures throughout childhood. Genetic counseling is recommended for families with children who have galactosemia.
Research is continuing into the use of the drug ureline as a possible treatment for galactosemia. More study is needed to determine the long-term safety and effectiveness of the use of this drug. For more information on this study, contact:
Francine Kaufman, M.D.
Children’s Hospital of Los Angeles
4650 Sunset Blvd.
Los Angeles, CA 90027
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
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