$Unique_ID{BRK03760} $Pretitle{} $Title{Galactosemia} $Subject{Galactosemia Galactose-1-Phosphate Uridyl Transferase Deficiency GALT Deficiency Lactose Intolerance Lactase Deficiency Disaccharidase Deficiency Glucose-Galactose Malabsorption Alactasia } $Volume{} $Log{} Copyright (C) 1987, 1990, 1991 National Organization for Rare Disorders, Inc. 373: Galactosemia ** IMPORTANT ** It is possible the main title of the article (Galactosemia) is not the name you expected. Please check the SYNONYMS listing to find the alternate names, disorder subdivisions, and related disorders covered by this article. Synonyms Galactose-1-Phosphate Uridyl Transferase Deficiency GALT Deficiency Information on the following diseases can be found in the Related Disorders section of this report: Lactose Intolerance, also known as Lactase Deficiency, Disaccharidase Deficiency, Glucose-Galactose Malabsorption, or Alactasia General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Galactosemia is an autosomal recessive hereditary disorder of carbohydrate metabolism. It is a rare inability to convert galactose (a sugar contained in milk) to glucose (a different type of sugar). The disorder is caused by a deficiency of the enzyme "galactose-1-phosphate uridyl transferase". A Duarte and a Negro variant of the Galactosemia gene have been identified. The Duarte variant causes a milder form of the disorder, while the Negro variant causes a more severe form. These variants can be distinguished by differences in galactose metabolism. Since milk is the main staple of an infant's diet, early diagnosis and treatment of this disorder is absolutely essential to avoid serious lifelong disability. Symptoms An infant with Galactosemia appears normal at birth, but within a few days or weeks loses its appetite (anorexia) and starts vomiting excessively. Yellow 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. 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 have arrested physical and mental development with possible vision loss due to cataracts. In severe cases overwhelming infection can be life threatening, but mild cases may exhibit few symptoms without serious impairment. An infant with Galactosemia should be treated promptly by removing galactose totally from the diet. Liver and kidney failure, brain damage and cataracts can be prevented through avoidance of galactose. 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. Girls with Galactosemia may develop impaired functioning of the ovaries because of an increased level of the hormone gonadotropin; two males with Galactosemia have also been identified who have an excessive level of gonadotropin (hypergonadotropinism). Causes 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 a milk sugar called galactose. Two different toxic products in galactosemic patients have been identified: galactitol and galactose-1-phosphate. Galactitol causes cataracts, while galactose-1-phosphate causes the other symptoms. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will show no symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent and will be genetically normal. Affected Population About 1 in 80,000 live births have been estimated to be affected with Galactosemia in Great Britain. As many males as females are affected. Related Disorders Lactose Intolerance (Lactase Deficiency, Disaccharidase Deficiency, Glucose- Galactose Malabsorption, or Alactasia) is characterized by diarrhea and abdominal distention. A lack of the enzyme "lactase" that normally helps to split milk sugar (lactose) into glucose and galactose, prevents absorption of lactose in the small bowel. This is a very common hereditary disorder, especially in adults with ancestry from Mediterranean, East European, and African origin. (For more information on this disorder, choose "Lactose Intolerance" as your search term in the Rare Disease Database.) However, the symptoms of Lactose Intolerance which usually get worse with increasing age may cause discomfort without permanent disability in contrast to Galactosemia which is a more debilitating illness. Therapies: Standard Pregnant women who are carriers for Galactosemia (without symptoms) can be detected by testing 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. Galactosemia can be diagnosed in infants at birth by testing the enzyme activity level in red blood cells in a drop of blood from the umbilical cord. Milk and milk products should be eliminated from the diet of children with Galactosemia and pregnant women who are known carriers of the disorder since the lactose in milk is digested to form galactose. Galactose in the mother's blood can cause brain damage to an unborn baby with Galactosemia in the uterus. After birth, an affected child's diet should contain lactose- free milk substitutes, and foods such as casein hydrolysates and soy bean products. Strict dietary restriction should be maintained until the patient is at least 2 years old and 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 may be necessary to control infection. The emotional effects of the strict diet may require attention throughout childhood. Genetic counseling is recommended for families of Galactosemia patients. Therapies: Investigational In 1989, Dr. Francine Kaufman, Children's Hospital of Los Angeles, 4650 Sunset Blvd., Box #61, Los Angeles, 90027, received a research grant from the National Organization for Rare Disorders (NORD) to study the use of Ureline as a treatment for Galactosemia. More research is needed to determine the safety and effectiveness of this experimental medication. For more information, physicians may contact Dr. Kaufman at the above address. This disease entry is based upon medical information available through February 1991. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Galactosemia, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Parents of Galactosemic Children, Inc. 20981 Solano Way Boca Raton, FL 33433 (407) 852-0266 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. Crewe CW1 1XN, England Telephone: (0270) 250244 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References GALACTOSEMIA: HOW DOES LONG-TERM TREATMENT CHANGE THE OUTCOME?: R. Gitzelmann, et. al.; Enzyme (1984: issue 32,1). Pp. 37-46. BIRTH DEFECTS COMPENDIUM, 2nd ed: Daniel Bergsma, ed; March of Dimes, 1979. Pp. 455-456.