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Related to Galactose epimerase deficiency: Galactosemia type 3, GALE deficiency




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.


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.

Causes and symptoms

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.

Galactosemia iii

Galactosemia III is caused by defects in the gene that codes for an enzyme called uridyl diphosphogalactose-4-epimerase (GALE). This form of galactosemia is very rare.
There are two forms of galactosemia III, a severe form, which is exceedingly rare, and a benign form. The benign form has no symptoms and requires no special diet. However, newborns with galactosemia III, including the benign form, have high levels of galactose-1-phosphate that show up on the initial screenings for elevated galactose and galactose-1-phosphate. This situation illustrates one aspect of the importance of follow-up enzyme function tests. Tests showing normal levels of GALT and GALK allow people affected by the benign form of galactosemia III to enjoy a normal diet.
The severe form has symptoms similar to those of galactosemia I, but with more severe neurological problems, including seizures. Only two cases of this rare form had been reported as of 1997.


The newborn screening test for classic galactosemia is quick and straightforward; all but three states require testing on all newborns. Blood from a baby who is two to three days old is usually first screened for high levels of galactose and galactose-1-phosphate. If either of these compounds is elevated, further tests are performed to find out which enzymes (GALT, GALK, or GALE) are present or missing. DNA testing may also be performed to confirm the diagnosis.
If there is a strong suspicion that a baby has galactosemia, galactose is removed from the diet right away. In this case, an initial screen for galactose or galactose-1-phosphate will be meaningless. In the absence of galactose in the diet, this test will be negative whether the baby has galactosemia or not. In this case, tests to measure enzyme levels must be given to find out if the suspected baby is indeed galactosemic.
In addition, galactosemic babies who are refusing milk or vomiting will not have elevated levels of galactose or galactose phosphate, and their condition will not be detected by the initial screen. Any baby with symptoms of galactosemia (for example, vomiting) should be given enzyme tests.


Galactosemia I and II are treated by removing galactose from the diet. Since galactose is a breakdown product of lactose, the primary sugar constituent of milk, this means all milk and foods containing milk products must be totally eliminated. Other foods like legumes, organ meats, and processed meats also contain considerable galactose and must be avoided. Pills that use lactose as a filler must also be avoided. Soybased and casein hydrolysate-based formulas are recommended for infants with galactosemia.
Treatment of the severe form of galactosemia III with a galactose-restricted diet has been tried, but this disorder is so rare that the long-term effects of this treatment are unknown.


Early detection in the newborn period is the key to controlling symptoms. Long-term effects in untreated babies include severe mental retardation, cirrhosis of the liver, and death. About 75% of the untreated babies die within the first two weeks of life. On the other hand, with treatment, a significant proportion of people with galactosemia I can lead nearly normal lives, although speech defects, learning disabilities, and behavioral problems are common. A 2004 study revealed that children and adolescents with classic galactosemia often have lower quality of life than peers without the disease, exhibiting problems with cognition (thinking and intellectual skills) and social function. In addition, cataracts due to galactosemia II can be completely prevented by a galactose-free diet.

Key terms

Casein hydrolysate — A preparation made from the milk protein casein, which is hydrolyzed to break it down into its constituent amino acids. Amino acids are the building blocks of proteins.
Catalyst — A substance that changes the rate of a chemical reaction, but is not physically changed by the process.
Enzyme — A protein that catalyzes a biochemical reaction or change without changing its own structure or function.
Galactose — One of the two simple sugars, together with glucose, that makes up the protein, lactose, found in milk. Galactose can be toxic in high levels.
Glucose — One of the two simple sugars, together with galactose, that makes up the protein, lactose, found in milk. Glucose is the form of sugar that is usable by the body to generate energy.
Lactose — A sugar made up of of glucose and galactose. It is the primary sugar in milk.
Metabolic pathway — A sequence of chemical reactions that lead from some precursor to a product, where the product of each step in the series is the starting material for the next step.
Metabolism — The total combination of all of the chemical processes that occur within cells and tissues of a living body.
Recessive trait — An inherited trait or characteristic that is outwardly obvious only when two copies of the gene for that trait are present.


Since galactosemia is a recessive genetic disease, the disease is usually detected on a newborn screening test, since most people are unaware that they are carriers of a gene mutation causing the disease. For couples with a previous child with galactosemia, prenatal diagnosis is available to determine whether a pregnancy is similarly affected. Families in which a child has been diagnosed with galactosemia can have DNA testing which can enable other more distant relatives to determine their carrier status. Prospective parents can then use that information to conduct family planning or to prepare for a child with special circumstances. Children born with galactosemia should be put on a special diet right away, to reduce the symptoms and complications of the disease.



Bosch, Annet M., et al. "Living With Classical Galactosmeia: Health-related Quality of Life Consequences." Pediatrics May 2004: 1385-1387.


Association for Neuro-Metabolic Disorders. 5223 Brookfield Lane, Sylvania, OH 43560. (419) 885-1497.
Metabolic Information Network. PO Box 670847, Dallas, TX 75367-0847. (214) 696-2188 or (800) 945-2188.
Parents of Galactosemic Children, Inc. 2148 Bryton Dr., Powell OH 43065.


"GeneCards: Human Genes, Proteins and Diseases."
"Vermont Newborn Screening Program: Galactosemia." 〈∼m145037/vhgi_mem/nbsman/galacto.htm〉.
Gale Encyclopedia of Medicine. Copyright 2008 The Gale Group, Inc. All rights reserved.


a genetically determined biochemical disorder in which there is a lack of an enzyme necessary for proper metabolism of galactose. Normally the lactose in milk is initially broken down into its glucose and galactose components. The galactose is then changed by enzymatic action into glucose. When the conversion of galactose to glucose does not take place, the galactose accumulates in the tissues and blood. There are two types: classic galactosemia and galactokinase deficiency.

Classic galactosemia is due to a deficiency of the enzyme galactose-1-phosphate uridyl transferase, and is transmitted as an autosomal recessive trait. The disorder becomes manifest soon after birth and is characterized by feeding problems, vomiting and diarrhea, abdominal distention, enlargement of the liver, mental retardation, and elevated blood and urine levels of both galactose and galactose-1-phosphate.

Galactosemia is diagnosed by demonstrating that the activity of the enzyme galactose-1-phosphate uridyltransferase is absent. If the disease is detected early, before there is damage to the central nervous system, the symptoms of the disorder can be prevented. Genetic counseling is important for families affected by this disorder.

Treatment consists of exclusion from the diet of milk and all foods containing galactose or lactose. Milk substitutes are used and the diet is planned to substitute necessary nutrients normally obtained from products containing lactose or galactose.
Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved.


1. An inborn error of galactose metabolism due to congenital deficiency of the enzyme galactosyl-1-phosphate uridylyltransferase, resulting in tissue accumulation of galactose 1-phosphate; manifested by nutritional failure, hepatosplenomegaly with cirrhosis, cataracts, mental retardation, galactosuria, aminoaciduria, and albuminuria that regress or disappear if galactose is removed from the diet; autosomal recessive inheritance; caused by mutation in the galactose 1-phosphate uridyltransferase gene (GALT) on 9p.
See also: galactokinase deficiency.
2. An inborn error in metabolism other than a deficiency in galactosyl-1-phosphate uridylyltransferase (see subentries below).
Synonym(s): galactose diabetes
[galactose + G. haima, blood]
Farlex Partner Medical Dictionary © Farlex 2012


An inherited metabolic disorder characterized by deficiency of an enzyme necessary for the metabolism of galactose, a sugar found in milk, milk products, many legumes, and organ meats. The disorder results in elevated levels of galactose in the blood and can lead to intellectual disability and eye and liver abnormalities.

ga·lac′to·se′mic adj.
The American Heritage® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company. Published by Houghton Mifflin Company. All rights reserved.


Neonatology An AR condition characterized by defective metabolism of galactose, due to a lack of galactosyl-1-phosphate uridyltransferase, with accumulation of galactose-1-phosphate, detected by prenatal screening Clinical Hepatosplenomegaly, cirrhosis, mental retardation, cataracts Lab Albuminuria, aminoaciduria, galactosuria, ↑ in galactose, galactose-1-phosphate, galactitol Management Eliminate galactose from diet Prognosis Fatal, if undetected
McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc.


An inborn error of galactose metabolism due to congenital deficiency of the enzyme galactosyl-1-phosphate uridyltransferase, resulting in tissue accumulation of galactose 1-phosphate; manifested by nutritional failure, hepatosplenomegaly with cirrhosis, cataracts, mental retardation, galactosuria, aminoaciduria, and albuminuria, which regress or disappear if galactose is removed from the diet.
Synonym(s): galactosaemia.
[galactose + G. haima, blood]
Medical Dictionary for the Health Professions and Nursing © Farlex 2012


(gă-lak'tō-sē'mē-ă) [MIM*230400]
An inborn error of galactose metabolism due to congenital deficiency; of tissue accumulation of galactose 1-phosphate; manifested by nutritional failure, hepatosplenomegaly with cirrhosis, cataracts, mental retardation, galactosuria, aminoaciduria, and albuminuria.
Synonym(s): galactosaemia.
[galactose + G. haima, blood]
Medical Dictionary for the Dental Professions © Farlex 2012
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