About galactosemia

What is galactosemia?

Galactosemia is a rare, hereditary disorder of carbohydrate metabolism that affects the body's ability to convert galactose (a sugar contained in milk, including human mother's milk) to glucose (a different type of sugar). Galactose is converted to glucose by a series of three enzyme reactions. The disorder is caused by a deficiency of an enzyme known as "galactose-1-phosphate uridyl transferase" which is vital to this process.

Galactosemia may also be referred to as classic galactosemia because a few variants of the gene for galactosemia have been identified. One variant causes a milder form of the disorder known as Duarte galactosemia. Classic galactosemia is the most severe form.

Because milk is the staple of an infant's diet, early diagnosis and treatment of this disorder is absolutely essential to avoid serious lifelong disability.

What are the symptoms for galactosemia?

An infant with galactosemia appears normal at birth, but within a few days or weeks loses their appetite and starts Vomiting excessively. Yellowing of the skin, mucous membranes, and whites of the eyes (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) with abdominal swelling (edema) may also occur. Diarrhea, Irritability, Lethargy and a bacterial infection may also be early signs of galactosemia. In time, wasting of body tissues, marked Weakness, and extreme Weight loss occur unless lactose is removed from the diet.

Children with galactosemia who have not received early treatment may show arrested physical and mental development and are particularly susceptible to cataracts in infancy or childhood. In severely affected children, overwhelming infection in the newborn period can cause life-threatening complications, but children with Duarte variant galactosemia may have few signs and no serious impairment(s).

In order to avoid the consequences of galactosemia, which may include liver failure and kidney dysfunction, brain damage and/or cataracts, infants must be treated promptly by removing lactose from the diet. Children treated with this special diet may still experience complications. Speech and learning difficulties and some behavioral problems are still likely to occur. Ovarian impairment is almost always seen in girls with classic galactosemia and is associated with an increase in the blood level of the gonadotropin hormone, follicle-stimulating hormone (FSH); males with galactosemia do not usually exhibit abnormalities in gonadal function.

The above-mentioned complications associated with classic galactosemia and clinical variant galactosemia have not occurred in individuals with Duarte variant galactosemia, a type of biochemical variant galactosemia. However, in a minority of these children, developmental delay and/or a speech abnormality has occurred, but it is unclear whether this is related to accumulation of galactose and its metabolites. Individuals with Duarte variant galactosemia do not need to maintain a special diet.

What are the causes for galactosemia?

Galactosemia occurs due to disruptions or changes (mutations) in the GALT gene resulting in deficiency of the GALT enzyme. This leads to abnormal accumulation of galactose-related chemicals in various organs of the body causes the signs and symptoms and physical findings of galactosemia.

The GALT enzyme is needed for the breakdown of the milk sugar, galactose. Deficiency of this enzyme results in the accumulation of toxic products: galactose-1-phosphate (a derivative of galactose) and galactitol (an alcohol derivative of galactose). Galactitol accumulates in the lens of the eye where it causes lens swelling and protein precipitation and subsequently, cataracts. Accumulation of galactose-1-phosphate is thought to cause the other signs and symptoms of disease.

Galactosemia is an autosomal recessive genetic disorder. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.

What are the treatments for galactosemia?

Infants and children with galactosemia should have a lactose-restricted (dairy-free) diet that contains lactose-free milk substitutes and other foods such as soybean products.

A lactose tolerance test should NOT be administered to children with galactosemia. Fortunately, infants with galactosemia can synthesize galactolipids and other essential galactose-containing compounds without the presence of galactose in food. Therefore, satisfactory physical development is largely possible if a strict diet is followed.

Speech therapy may be necessary for children with childhood apraxia of speech or dysarthria. For school age children, individual education plans and/or professional help with learning skills may be necessary for some individuals, depending on psychological developmental assessments. Hormone replacement therapies may also be used in cases of delayed puberty and later in adolescence for the secondary loss of menstrual periods, termed premature ovarian insufficiency (POI).

Appropriate treatment (i.e., antibiotic drugs) may be used to control infection in the newborn period. The emotional effects of the strict diet may require attention and supportive measures throughout childhood.

Genetic counseling is recommended for families with children who have galactosemia.

Following several conferences, a consensus on the treatment and follow-up of patients with galactosemia was published in 2017.

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