Galactosemia and genetics
Galactosemia is a rare inherited disorder caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase, which is essential for converting galactose, a sugar found in milk, into glucose, the body's main energy source. This condition results from mutations in the GALT gene located on chromosome 9, and it follows an autosomal recessive inheritance pattern, meaning that both parents must be carriers for a child to be affected. Symptoms typically appear in infancy, manifesting as jaundice, poor feeding, irritability, and lethargy, often worsening without dietary intervention. If untreated, galactosemia can lead to severe complications such as liver damage, intellectual disabilities, and cataracts.
Currently, there is no cure for galactosemia, but strict dietary management—avoiding all sources of galactose, particularly milk and its derivatives—can help mitigate symptoms and prevent acute toxicity. Newborn screening programs can detect galactosemia early, allowing for timely dietary adjustments. Genetic counseling is advisable for families with a history of the disorder as they plan for future children. Overall, understanding galactosemia and its genetic basis is crucial for affected individuals and their families to manage the condition effectively.
Galactosemia and genetics
DEFINITION Classic galactosemia is an inherited disease. Due to a defective gene, there is a deficiency of the enzyme galactose-1-phosphate uridyltransferase, which is necessary for the conversion of galactose to glucose. Galactose is a simple sugar found in milk products. (The main sugar in milk, lactose, is made up of two simple sugars: galactose and glucose.) Glucose is the usable form of sugar in the human body.
Normally, the body converts galactose-1-phosphate into glucose, which it then uses for energy. In galactosemia, galactose builds up in the blood. A buildup of galactose-1-phosphate can cause severe damage to the liver, kidneys, central nervous system, and other body systems. If undetected, galactosemia is fatal. A less severe form of this disease is due to galactokinase deficiency. This type may be managed with a few dietary restrictions and does not carry the risk of neurologic or liver damage. However, the eye lens may be damaged, which can lead to cataracts.
Risk Factors
The primary risk factor for galactosemia is having parents who carry the genes for this condition.
Etiology and Genetics
Classic galactosemia (type I) results from a mutation in the GALT gene, which is located on the short arm of chromosome 9 at position 9p13. This gene encodes the galactose-1-phosphate uridyltransferase, which normally catalyzes an essential step in the conversion of galactose to glucose. The most common mutations in the GALT gene result in the production of a completely nonfunctional enzyme. It is the accumulation of galactose and related metabolites in tissues that causes the severe symptoms associated with the disease.
Two other genes specify enzymes in the galactose breakdown pathway, and other less common forms of galactosemia (types II and III) can result if there are mutations in either of these genes. GALK1, on chromosome 17 at position 17q24, encodes the enzyme galactokinase-1, and GALE, on the short arm of chromosome 1 at position 1p36-p35, codes for the enzyme UDP-galactose-4-epimerase.
For all types of galactosemia, the inheritance pattern is characteristic of an autosomal recessive mutation. Both copies of the gene must be deficient in order for the individual to be afflicted. Typically, an affected child is born to two unaffected parents, both of whom are carriers of the recessive mutant allele. The probable outcomes for children whose parents are both carriers are 75 percent unaffected and 25 percent affected. If one parent has galactosemia and the other is a carrier, there is a 50 percent probability that each child will be affected
Symptoms
An infant with classic galactosemia usually appears normal at birth. If galactosemia is not detected at birth with testing, symptoms usually occur within the first few days or weeks of life after the baby drinks breast milk or a lactose-containing formula. Early symptoms may include jaundice (yellowing) of the skin and whites of the eyes, vomiting, poor weight gain, low blood sugar (hypoglycemia), feeding difficulties, irritability, lethargy, and convulsions.
If left untreated, later signs and symptoms may include opaque lenses of the eyes (cataracts), enlarged liver, enlarged spleen, intellectual disabilities, sepsis caused by a specific bacteria (Escherichia coli), cirrhosis (scarring of the liver), liver failure, kidney problems, and swelling of the extremities or stomach.
If dietary restrictions are started immediately, it may be possible to prevent acute toxicity. However, long-term complications may still occur. These may include poor growth, learning disabilities, speech and language problems, fine and gross motor-skill delays, ovarian failure (in girls), cataracts (usually regress with dietary treatment, leaving no residual visual impairment), and decreased bone mineral density.
Screening and Diagnosis
Most American infants are screened for galactosemia at birth with a simple blood test. A small sample of blood is taken with a heel prick. It is also possible to diagnose galactosemia during pregnancy with an amniocentesis. With the proper testing, galactosemia is detectable in almost all cases through these newborn screenings.
The diagnosis may also be suggested if a urine test shows the presence of a reducing substance. The diagnosis can be confirmed with a blood test or with a biopsy of the liver or other tissues.
Treatment and Therapy
Galactosemia cannot be cured. However, patients can take steps to prevent or minimize galactosemia symptoms and complications. The treatment is the strict avoidance of all sources of galactose. The most common source is lactose, which is the milk sugar that breaks down to galactose and glucose.
To avoid all sources of galactose, patients should closely monitor their diets. They should avoid all products that contain or produce galactose. This includes milk as well as milk by-products such as casein, lactose (milk sugar), dry milk solids, curds, and whey. It also includes some non-milk products, such as fermented soy products, legumes, organ meats, and hydrolyzed protein.
Lactose or galactose may be used as an additive in some food products. Therefore, patients should always read food labels carefully in order to avoid these foods. Because galactose is so commonly found in foods, parents of a child who has galactosemia will nearly always require the services of a dietitian skilled in advising about the management of this rare disorder.
Patients should check with their pharmacists to avoid medications that have fillers containing galactose or lactose. They should also avoid supplements, unless prescribed by their doctors, as fillers and inactive ingredients are not required to be listed in supplements. If patients do take supplements, they should check with their pharmacists to ensure that there are no hidden sources of galactose in the product.
Prevention and Outcomes
There is no known way to prevent galactosemia. Individuals who have galactosemia or have a family history of the disorder can talk to a genetic counselor when deciding to have children.
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