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.

• The incidence of galactosemia varies in different populations. In the United Kingdom, one in 70,000 individuals is affected. In the United States, one in 60,000 individuals is affected. One in 30,000 individuals is affected in Ireland. Galactosemia is thought to be very rare in Asian populations.
• Because galactosemia is inherited, the only known risk factor is a family history of the disorder. Galactosemia is inherited as an autosomal recessive trait. Individuals have two copies of most genes, one inherited from the father and one from the mother. To inherit a recessive genetic disorder, an individual must receive two copies of the defective gene for the disease to appear.
• People who have only one mutated gene are called "carriers." If only one parent is a carrier, none of the children will have galactosemia, but each child will have a 50% chance of being a carrier; if both parents are carriers, then each child has a 50% chance of being a carrier, a 25% chance of not inheriting either mutated gene, and a 25% chance of having galactosemia.

• Galactosemia may be caused by mutations or defects in any of three genes: galactokinase 1 (GALK1), UDP-galactose-4-epimerase (GALE), or galactose-1-phosphate uridyl transferase (GALT). Most commonly, galactosemia is caused by a mutation in the GALT gene. The GALT gene normally provides instructions for making an enzyme that functions in liver cells to break down the sugar galactose. Galactose is normally broken down into another sugar called glucose, which is used by the body to generate energy.
• Mutations in the GALT gene result in either reduced or absent enzymatic activity, which leads to an inability to break down galactose. Galactose therefore builds up in the body and may cause damage to the eyes, brain, liver, or kidneys.
• Both GALK1 and GALE provide instructions for making proteins that break down galactose in the body. Mutations in the GALK1 or GALE gene therefore cause galactosemia in the same way as mutations in the GALT gene, through a loss of enzymatic activity and a buildup of galactose.

• Soon after birth, infants with galactosemia may develop weakness, diarrhea, or vomiting, commonly after consuming milk. Some infants may refuse to eat and could have difficulty putting on weight. Symptoms may develop very soon after birth, and in some cases appear within several days in infants who consume milk or other foods containing lactose or galactose.
• Patients may develop problems with the liver, including enlargement and cirrhosis, a condition in which scar tissue replaces healthy liver tissue. Liver failure, which could be life-threatening, may occur in some patients. Jaundice, an abnormal yellow coloring of the skin and eyes, is a sign of liver failure that some patients may experience.
• If untreated, patients with galactosemia may develop bacterial infections. E. coli infections are especially common in infants, and can lead to death if not treated. Infections may be caused by damage to the intestinal wall by the buildup of galactose.

• Galactosemia may become life-threatening shortly after birth if not properly treated, which makes early and accurate diagnosis critical.
• Blood tests: Galactosemia may be diagnosed in newborns right after birth using blood tests. This is the most common way to diagnose the condition, and screening for galactosemia is routine in the United States. In one type of screening test, blood is analyzed for the levels of the enzymes GALT, GALE, or GALK1. If any of these enzyme levels is abnormally low, the patient may be diagnosed with galactosemia. Another type of screening test measures the level of galactose in a patient's blood. Abnormally high galactose levels may suggest that the patient has galactosemia.
• Genetic testing: If galactosemia is suspected, a cytogenetic test may be performed to confirm a diagnosis. A sample of the patient's blood is analyzed in a laboratory for the defect in the GALT, GALE, or GALK1 genes. If any of these mutations are detected, a positive diagnosis is made.
• Prenatal DNA testing: If there is a family history of galactosemia, prenatal testing may be performed to determine whether the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) can diagnose galactosemia. However, because there are serious risks associated with these tests, patients should discuss the potential health benefits and associated risks with a medical professional.
• During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus, and a small amount of amniotic fluid is removed from the sac surrounding the fetus. Cells in the fluid are then analyzed for normal and abnormal chromosomes. This test can be performed after 15 weeks of pregnancy. The risk of miscarriage is about one in 200 to 400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.
• During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the placenta between the ninth and 14th week of pregnancy. CVS may be performed through the cervix or through the abdomen. The cells in the tissue sample are then analyzed for mutations in the causative genes. Miscarriage occurs in about 0.5 to 1% of women who undergo this procedure.

• Cataracts: Some individuals with galactosemia may develop cataracts, a clouding or opaqueness of the lens of the eye. People with galactosemia may develop cataracts because of increased levels of galactose and the conversion of galactose to the alcohol galactitol in the eye. The diffusion of galactitol causes swelling and increased pressure in the eye lens, which can lead to cataracts. Once dietary intake of lactose and galactose is restricted, cataracts usually clear up.
• Neurological problems: Some people with galactosemia develop neurological problems, even if they follow a lactose and galactose-free diet. Patients with galactosemia may have learning disabilities, such as difficulty learning speech or language, or they may have impaired motor skills, such as difficulty walking or maintaining balance. Some patients also exhibit involuntary muscle movements (tremors), especially in the hands.
• Ovarian failure: About 60% of females with galactosemia develop ovarian failure. In these patients, the ovaries stop working, which causes infertility. The reason for premature ovarian failure in patients with galactosemia is currently not known.

• Currently there is no known cure for galactosemia. Treatment generally focuses on managing the symptoms and preventing complications.
• Antibiotics: Antibiotics may be necessary for patients who develop infections. Most commonly, patients need antibiotics for E. coli bacterial infections. Streptomycin, which may be taken orally or through injection, is commonly used to fight E. coli infections.
• Blood tests: Blood tests are used throughout the lives of individuals with galactosemia to monitor the level of galactose in the blood. In these tests, a sample of blood is withdrawn, and an analysis is performed to measure the galactose level. Blood tests are usually recommended about once a year in adults, but more frequently in infants.
• Diet: Because galactose is derived from lactose, patients with galactosemia are unable to digest lactose- or galactose-containing foods. People with galactosemia should therefore not consume foods containing lactose or galactose throughout their entire lives. Foods that contain lactose or galactose include milk, cheese, butter, and other dairy products. Infants with galactosemia may be given milk made from soybeans. Individuals with galactosemia may benefit from consulting a nutritionist, who can help plan a diet that does not contain lactose or galactose and that still meets all nutritional requirements.
• Dietary supplements: Milk is a major source of calcium, as well as vitamin D and other nutrients. Because patients with galactosemia must avoid most dairy products, they may need calcium, vitamin D, and other dietary supplements.
• MedicAlert® bracelets: Patients may wear bracelets that alert others to the fact that they have galactosemia. These bracelets are most commonly worn by children, who may be away from their parents or caregivers during school, daycare, or other activities.
• Surgery: In some individuals, cataracts may clear up once dietary intake of lactose and galactose is restricted. However, if cataracts do not clear up, surgical removal of the cataracts may be necessary.

Note
: Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of galactosemia. The therapies listed below have been studied for related conditions such as calcium and vitamin D deficiency. The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider and should not be used in replacement of other proven therapies.

A

Strong scientific evidence

• Calcium
  : Calcium gluconate is used to treat conditions arising from calcium deficiencies such as hypocalcemic (low blood calcium) tetany (muscle spasms), hypocalcemia related to hypoparathyroidism (low levels of the parathyroid hormone), and hypocalcemia due to rapid growth or pregnancy. It is also used for the treatment of hypocalcemia for conditions requiring a prompt increase in plasma calcium levels (e.g., tetany in newborns and tetany from parathyroid deficiency, vitamin D deficiency, and alkalosis) and for the prevention of hypocalcemia during exchange transfusions. Treatment of hypocalcemia should be done only under the supervision of a qualified healthcare professional. Calcium supplementation has not been studied specifically in people with galactosemia.
• Avoid if allergic or hypersensitive to calcium or lactose. High doses taken by mouth may cause kidney stones. Avoid with hypercalcemia (high levels of calcium in the blood), hypercalciuria (high levels of calcium in urine), hyperparathyroidism (high levels of parathyroid hormone), bone tumors, digitalis toxicity, ventricular fibrillation (ventricles of the heart contracting in an unsynchronized rhythm), kidney stones, kidney disease, or sarcoidosis (inflammation of lymph nodes and various other tissues). Calcium supplements made from dolomite, oyster shells, or bone meal may contain unacceptable levels of lead. Use cautiously with achlorhydria (absence of hydrochloric acid in gastric juices) or arrhythmia (irregular heartbeat). Calcium appears to be safe in pregnant or breastfeeding women; it is recommended to consult with a healthcare provider to determine appropriate dosing during pregnancy and breastfeeding.
• Vitamin D
  : Adults with severe vitamin D deficiency lose bone mineral content (hypomineralization) and experience bone pain, muscle weakness, and osteomalacia (soft bones). Osteomalacia may be seen in elderly patients with vitamin D-deficient diets, individuals with decreased absorption of vitamin D, individuals with inadequate seasonal sun exposure, patients with gastric or intestinal surgery, patients with aluminum-induced bone disease, patients with chronic liver disease, or patients with kidney disease with renal osteodystrophy. Treatment for osteomalacia depends on the underlying cause of the disease and often includes pain control and orthopedic surgical intervention, as well as vitamin D and phosphate binding agents. Without sufficient vitamin D, inadequate calcium is absorbed and the resulting elevated parathyroid (PTH) secretion causes increased bone resorption. This may weaken bones and increase the risk of fracture. Vitamin D supplementation has been shown to slow bone loss and reduce fracture, particularly when taken with calcium. Vitamin D supplementation has not been specifically studied in people with galactosemia.
• Avoid if allergic or hypersensitive to vitamin D or any of its components. Vitamin D is generally well-tolerated in recommended dosages, but higher than recommended dosages may cause toxic effects. Use cautiously with hyperparathyroidism (overactive thyroid), kidney disease, sarcoidosis, tuberculosis, and histoplasmosis. Vitamin D is safe in pregnant and breastfeeding women when taken in recommended dosages.

• General: Because galactosemia is an inherited condition, there is currently no known way to prevent the disease. However, a number of options are available for parents with family histories of galactosemia.
• Genetic testing and counseling: Individuals who have galactosemia may meet with a genetic counselor to discuss the risks of having children with the disease. Individuals with a family history of galactosemia may meet with a genetic counselor to determine whether they carry the defective GALT, GALE, or GALK1 genes. Carriers can be determined through detailed family histories or genetic testing.
• Known carriers of galactosemia may undergo genetic counseling before they conceive a child. A genetic counselor can explain the options and associated risks of various tests, including pre-implantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS).
• Pre-implantation genetic diagnosis (PGD) may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the defective GALT, GALE, or GALK1 genes, and only the unaffected embryos are implanted. Because galactosemia can be detected in a fetus, parents may choose whether to continue the pregnancy. A genetic counselor can assist parents with these difficult decisions.