galactosemia

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More about Galactosemia: Causes and symptoms Diagnosis Treatment Prognosis Prevention Resources

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.

— Amy Vance, MS, CGC

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.

An inherited condition that prevents normal metabolism of galactose due to a lack of the galactose-l-phosphate uridyl transferase enzyme.

Definition

Galactosemia is an inherited disease in which the body is unable to metabolize the simple sugar galactose, which is found primarily in dairy products but is also produced by the body. If left unaddressed, galactose can increase to toxic levels in the body and may lead to damage of the liver, central nervous system, and various other body systems.

Description

Galactosemia is a rare but potentially life-threatening disease resulting from the body's inability to metabolize galactose. Galactose makes up half of lactose, the sugar that is found in milk. Persons with galactosemia either have very low levels of or are entirely lack the enzyme that assists the body in breaking down galactose. This enzyme is called galactose-1-phosphate uridyl transferase (GALT). The GALT enzyme enables the body to break down galactose into glucose for energy. The severity of the disease may vary from person to person, because some individuals with galactosemia have higher levels of this enzyme than do others.

The two main types of galactosemia are called classic and Duarte variant. Individuals with the classic type of galactosemia lack the enzyme activity necessary to metabolize galactose. Individuals with the Duarte variant have approximately 5–20 percent of the enzyme activity necessary to metabolize this sugar and often do not have signs or symptoms of galactosemia.

Transmission

Galactosemia is an hereditary disease. In order to understand this disorder, it is necessary to have a very basic knowledge of genetics. Genes, the basic components of hereditary material, contain the "blueprint" that directs the development and functioning of every cell and tissue in the human body. Genes are situated on larger structures called chromosomes that contain several thousand genes each. Genes and chromosomes exist in pairs. Every cell in the body has 23 pairs of chromosomes containing two copies of every gene. Human beings receive one copy of every gene from their mother, and another copy from their father. Most of the time, genes function normally. However, in some cases, a change or mutation in a gene can cause it to not function. These mutations can cause inherited or genetic disorders.

In galactosemia, the gene mutation which occurs is inherited in what is known as an autosomal recessive pattern. This means that a non-working copy of the gene must be inherited from both parents for a child to be affected with the disease. The parents of children are called "carriers" of the disorder, because though they themselves do not have galactosemia, they may have children who do.

Unfortunately, as of 2004, parents had no way of knowing if they carry the mutated gene that causes galactosemia until they have a child diagnosed with the disease. The chance that two parents each of whom has the defective gene will produce a child with a recessive disorder is one in four or 25 percent with each pregnancy. The chances that their child will be a carrier, like themselves, is one in two, or 50 percent, with each pregnancy.

Demographics

Galactosemia is an inherited disorder that occurs in approximately one out of 30,000 live births. The incidence for the Duarte variant type of galactosemia is estimated to be one in 16,000 live births. Although galactosemia occurs in all ethnic groups worldwide, some mutations cause a less severe type of disease and are more commonly seen in specific ethnic groups, such as African-Americans. In Japan, classic galactosemia is not diagnosed as frequently as it is in Caucasian populations in the United States.

Causes and Symptoms

Galactosemia is an inherited disorder. People with the disease are unable to fully break down galactose. If an infant with galactosemia is given milk, byproducts of galactose will build up in the baby's body, causing damage to the liver, kidneys, brain, and eyes. Characteristically, a newborn with galactosemia who is fed milk products will have jaundice, vomiting, lethargy, irritability, and convulsions. Continued feeding of milk products to the infant will lead to cirrhosis, cataracts, kidney failure, and mental retardation.

When to Call the Doctor

Parents should notify their doctor if their child displays any of the symptoms of galactosemia. Couples should consult their physician if there is a family history of galactosemia, and they are considering having a child.

Diagnosis

As of late 2004, all 50 states had mandatory screening of newborns for galactosemia. If parents receive a call from a healthcare provider saying the screening test indicates possible galactosemia, they should promptly stop milk products and have a blood test done for galactosemia through their doctor. The physician may also perform enzyme studies on or look for the presence of "reducing substances" in the child's urine, look for ketones in the urine, and measure enzyme activity in the red blood cells.

Treatment

Galactosemia is treated by removing foods that contain galactose from the diet. Foods containing lactose and, therefore, galactose should be avoided. Because milk and milk products are the most common food source of galactose, persons with galactosemia should avoid ingesting these foods. It is recommended that persons with galactosemia avoid eating foods with galactose throughout their entire lives.

Nutritional Concerns

The goal of dietary treatment is to minimize galactose intake. It is impossible to have a galactose-free diet. However, all persons with galactosemia should limit galactose intake as much as possible. The galactose-1-phosphate levels of the individual will establish the level of dietary restriction necessary. Infants can be fed soy, meat-based, or other lactose-free formulas. Abstinence from milk and milk products must continue throughout life. Parents need to find some of the many listings available that identify the galactose content in foods. Since the primary source of calcium is usually milk or milk-based foods, calcium must be supplemented. Parents of a child with galactosemia should note that lactose is often used as filler in medicines. This very frequently is not listed on the package. Parents should always check with the pharmacist before administering any new medications.

Prognosis

Approximately 75 percent of the babies with galactosemia who are not diagnosed and treated die within the first two weeks of life. By contrast, if an early diagnosis is made and if milk products are strictly avoided, most children lead a relatively normal life. With appropriate treatment, liver and kidney problems do not develop, and early mental development progresses in a normal manner. However, even with proper treatment, children with galactosemia often have a lower intelligence quotient (IQ) than their siblings, and they frequently have speech problems. Girls often have ovaries that do not function, and only a few are able to conceive naturally. Boys, however, have normal testicular function.

Prevention

Since galactosemia is a recessive genetic disease, it is usually first detected on a newborn screening test, as most people are not aware that they are carriers of a gene mutation causing the disease. If there is a family history of galactosemia, genetic counseling is recommended for prospective parents as they make decisions regarding pregnancy and prenatal testing. Once one child in a family is diagnosed with galactosemia, it is recommended that other members of the family receive genetic counseling as well.

Parental Concerns

One of the most important things parents of a child with galactosemia can do is educate themselves thoroughly on an appropriate diet. All other caregivers or teachers involved with the child need to be notified of the child's dietary restrictions, and the potential consequences if they are not maintained.

Resources

Periodicals

Bosch, Annet M., et al. "Living with Classical Galactosemia: Health-Related Quality of Life Consequences." Pediatrics 113 (May 2004): 5.

Weese, S. Jean. "Galactose Content of Baby Food Meats: Considerations for Infants with Galactosemia." Journal of the American Dietetic Association (March 2003).

Organizations

National Newborn Screening and Genetics Resource Center. 1912 W. Anderson Lane, Suite 210, Austin, TX 78757. Web site: .

"Parents of Galactosemic Children Inc." 885 Del Sol St., Sparks, NV 89436. Web site: www.galactosemia.org.

Web Sites

"Galactosemia." MedlinePlus, January 2004. Available online at www.nlm.nih.gov/medlineplus/ency/article/000366.htm (accessed January 6, 2005).

"Galactosemia: An Overview." Adult Metabolic Transition Project. Available online at (accessed January 6, 2005).

[Article by: Deanna M. Swartout-Corbeil, RN]

A biochemical disorder in which there is a deficiency of enzymes necessary for proper metabolism of galactose. The condition is inherited in humans in two forms, due to deficiency of either galactokinase or galactose-1-phosphate uridyltransferase. Adult macropods are normally deficient in these enzymes.
Normally the sugar derived from lactose in milk is 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, typically causing cataract formation; commonly seen in young macropods reared on cow's milk.

Galactosemia
Classification and external resources
Galactose
ICD-10	E74.2
ICD-9	271.1
eMedicine	ped/818
MeSH	D005693

Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly.Galactosemia is sometimes confused with Lactose-Intolerance, but unlike lactose-intolerance, galactosemia is not something that someone can "grow out of." Once diagnosed, it is there for the rest of the persons life.

Goppert first described the disease in 1917,^[1] with its cause as a defect in galactose metabolism being identified by a group led by Herman Kalckar in 1956.^[2]

Its incidence is about 1 per 60,000 births (classic type). It is much rarer in Japan and much more common in Italy, specifically the traveler region. Galactosemia is also very common within the Irish Traveller population. This is attributed to consanguinity within a relatively small gene pool.^{[citation needed]}

Contents 1 Cause 2 Types 3 Diagnosis 4 Treatment 5 References 6 External links

Cause

Lactose

Glucose

Axial hydroxyl group drawn in red.

Lactose in food (such as dairy products) is broken down by the enzyme lactase into glucose and galactose. In individuals with galactosemia, the enzymes needed for further metabolism of galactose are severely diminished or missing entirely, leading to toxic levels of galactose in the blood, resulting in hepatomegaly (an enlarged liver), cirrhosis, renal failure, cataracts, brain damage, and ovarian failure. Without treatment, mortality in infants with galactosemia is about 75%.

Types

Galactose is converted into glucose by the action of three enzymes, known as the Leloir pathway. Accordingly, there are 3 known types of Galactosemia; type 1, 2 and 3:

Type	Diseases Database	OMIM	Gene	Locus	Enzyme	Name
Type 1	5056	230400	GALT	9p13	galactose-1-phosphate uridyl transferase	classic galactosemia
Type 2	29829	230200	GALK1	17q24	galactokinase	galactokinase deficiency
Type 3	29842	230350	GALE	1p36-p35	UDP galactose epimerase	galactose epimerase deficiency, UDP-Galactose-4-epimerase deficiency

The order of these three types is not the same as the order that the enzymes are encountered by galactose on its metabolic path (which is closer to GALK, GALT, and then GALE, though many variations can occur.)

Diagnosis

Infants are now routinely screened for galactosemia in the United States, and the diagnosis is made while the person is still an infant. Infants affected by galactosemia typically present with symptoms of lethargy, vomiting, diarrhea, failure to thrive, and jaundice. None of these symptoms are specific to galactosemia, often leading to diagnostic delays. Luckily, most infants are diagnosed on newborn screening. A galactosemia test is a blood test (from the heel of the infant) or urine test that checks for three enzymes that are needed to change galactose-a sugar that is found in milk and milk products-into glucose, a sugar that your body uses for energy. A person with galactosemia doesn't have one of these enzymes. This causes high levels of galactose in the blood or urine.

Treatment

The only treatment for classic galactosemia is eliminating lactose and galactose from the diet. Even with an early diagnosis and a restricted diet, however, some individuals with galactosemia experience long-term complications such as speech difficulties, learning disabilities, neurological impairment (e.g. tremors, etc), and in girls, ovarian failure. These complications are treated if they appear in a manner similar to the way they would be treated in a non-galactosemic. Such complications have not been associated with Duarte galactosemia, and many individuals with Duarte galactosemia do not need to restrict their diet at all. Infants with classic galactosemia cannot be breast-fed due to lactose in human breast milk and are usually fed a soy-based formula.^[3]

Galactosemia is sometimes confused with lactose intolerance, but galactosemia is a more serious condition. Lactose intolerant individuals have an acquired or inherited shortage of the enzyme lactase, and experience abdominal pains after ingesting dairy products, but no long-term effects. In contrast, a galactosemic individual who consumes galactose can cause permanent damage to their bodies.

Long term complication of galactosemia includes:

• Speech deficits
• Ataxia
• Dysmetria
• Diminished bone density
• Premature ovarian failure
• Cataract

References

1. ^ Goppert F. Galaktosurie nach Milchzuckergabe bei angeborenem, familiaerem chronischem Leberleiden. Klin Wschr 1917;54:473-477.
2. ^ Isselbacher KJ, Anderson EP, Kurahashi K, Kalckar HM (1956). "Congenital galactosemia, a single enzymatic block in galactose metabolism". Science 13 (123): 635–6. doi:10.1126/science.123.3198.635. PMID 13311516. 
3. ^ Breastfeeding: Diseases and Conditions: Contraindicators | DNPA

External links

• Galactosemia Resources and Information
• Parents of Galactosemic Children, Inc. website
• What is Galactosemia?
• Galactosemic Families of Minnesota
• Galactosemia Handbook - A Guide for Families
• galactosemia.org

v • d • e Inborn error of carbohydrate metabolism: monosaccharide metabolism disorders (including glycogen storage diseases) (E73-74, 271) Sucrose, transport (extracellular) Disaccharide catabolism Lactose intolerance · Sucrose intolerance Monosaccharide transport Glucose-galactose malabsorption · Inborn errors of renal tubular transport (Renal glycosuria) Hexose → glucose Monosaccharide catabolism fructose: Essential fructosuria · Fructose intolerance galactose/galactosemia : GALK deficiency · GALT deficiency/GALE deficiency Glucose ⇄ glycogen Glycogenesis GSD type 0, glycogen synthase · GSD type IV, Andersen's, branching Glycogenolysis extralysosomal: GSD type V, McArdle, muscle glycogen phosphorylase/GSD type VI, Hers', liver glycogen phosphorylase · GSD type III, Cori's, debranching lysosomal/LSD: GSD type II, Pompe's, glucosidase Glucose ⇄ CAC Glycolysis MODY 2 · GSD type VII, Tarui's, phosphofructokinase · Triosephosphate isomerase deficiency · Pyruvate kinase deficiency Pyruvate catabolism PDHA · Fumarase deficiency Gluconeogenesis PCD · Fructose bisphosphatase deficiency · GSD type I, von Gierke, glucose 6-phosphatase Pentose phosphate pathway Glucose-6-phosphate dehydrogenase deficiency · Pentosuria Other Hyperoxaluria (Primary hyperoxaluria) see also fructose and galactose metabolism enzymes, intermediates; see also glycolysis enzymes, intermediates see also glycogenesis and glycogenolysis enzymes, intermediates; see also pentose phosphate pathway enzymes, intermediates

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