Galactosemia: Symptoms, Causes, Diagnosis, Treatment

Galactosemia is a rare genetic disorder characterised by the body’s inability to break down galactose, a sugar in milk and dairy products. This condition is caused by mutations in specific genes that are involved in galactose metabolism. The most common form of galactosemia, known as classic galactosemia, is caused by mutations in the GALT gene. When galactose cannot be properly metabolised, it accumulates in the body, leading to various symptoms and potential complications.

Galactosemia can affect individuals of all ages, but it is typically detected in newborns through routine screening tests performed shortly after birth. Newborn screening programs aim to identify infants with elevated galactose levels or their byproducts in their blood. Early detection is crucial for timely intervention and management of the condition. If galactosemia is suspected, further diagnostic tests, such as genetic testing or enzyme activity assays, can be conducted to confirm the diagnosis and identify the specific gene mutations involved.

Symptoms

Galactosemia can manifest differently in individuals, but common symptoms may include:

• Failure to thrive and poor weight gain in infants
• Vomiting, diarrhea, and irritability after consuming milk or milk products
• Jaundice (yellowing of the skin and eyes)
• Liver problems, such as hepatomegaly (enlarged liver) or cirrhosis
• Developmental delays, speech difficulties, and learning disabilities
• Cataracts (clouding of the lens in the eye)

Causes 

Galactosemia is caused by mutations in specific genes that are involved in galactose metabolism. These mutations disrupt the production or function of enzymes required to break down galactose. The most common type of galactosemia is known as classic galactosemia, which is caused by mutations in the GALT gene. In rare cases, galactosemia can also be caused by mutations in other genes, such as GALE or GALK.

Diagnosis and Tests

Galactosemia is typically diagnosed through newborn screening programs, which involve a blood test shortly after birth. Elevated levels of galactose or its byproducts in the blood can indicate the presence of the disorder. Confirmatory diagnostic tests, such as genetic testing or enzyme activity assays, may be conducted to identify specific gene mutations or measure enzyme activity.

Types

• Classic Galactosemia: Classic galactosemia is the most common and severe condition. It is caused by mutations in the GALT gene, which provides instructions for producing an enzyme called galactose-1-phosphate uridylyltransferase. This enzyme is essential for breaking down galactose into glucose. In the absence or deficiency of this enzyme, galactose builds up in the body, leading to various symptoms and complications.
• Galactokinase Deficiency: Galactokinase deficiency(Type II Galactosemia) is a milder form of galactosemia caused by mutations in the GALK1 gene. This gene provides instructions for producing an enzyme called galactokinase, which converts galactose into galactose-1-phosphate. In individuals with galactokinase deficiency, galactose cannot be effectively converted, resulting in the accumulation of galactose in the blood and tissues. Compared to classic galactosemia, the symptoms of galactokinase deficiency are typically milder and may primarily involve the eyes, such as the development of cataracts.
• Galactose Epimerase Deficiency: Galactose epimerase deficiency is the rarest form of galactosemia, caused by mutations in the GALE gene. The GALE gene provides instructions for producing an enzyme called UDP-galactose-4-epimerase, which is involved in converting galactose to glucose and vice versa. In individuals with galactose epimerase deficiency, this conversion process is impaired, resulting in the accumulation of galactose in the body. The symptoms of galactose epimerase deficiency can vary but may include developmental delays, liver problems, and other complications similar to classic galactosemia.
• Duarte Galactosemia: Duarte galactosemia is a mild, usually asymptomatic form of galactosemia, a metabolic disorder. It is caused by a mutation in the GALT gene, but unlike classic galactosemia, the mutation only partially impairs the function of the GALT enzyme, which is responsible for processing galactose. This means that these people may have some digestive difficulties from foods containing galactose, but they don’t have the same medical complications. They don’t necessarily have to avoid galactose in their diet.

How does this condition affect my child’s body?

When the body is unable to break down the galactose in the food, it begins to build up in the blood. Galactosemia literally means “galactose in the blood.” When it builds up, it overflows into places it shouldn’t go. It reacts with an enzyme that is not supposed to be involved with it, which converts it to galactitol, an alcohol derivative that is toxic to the body. If left untreated, galactosemia leads to a cascade of side effects, which may include cataracts, developmental delays, intellectual disabilities, speech difficulties, fine and gross motor difficulties, neurological impairments, kidney disease, premature ovarian insufficiency, liver failure, or sepsis.

Children who receive an early diagnosis and treatment usually grow and develop adequately. Children receiving treatment for galactosemia may continue to have speech delays, learning disabilities, behavioural problems, balance and coordination problems (ataxia), tremors, hormone deficiencies, leading to delayed puberty in girls.

Possible Complications

Galactosemia, if not properly managed, can lead to a range of complications:

• Cataracts
• Cirrhosis of the liver
• Delayed speech development
• Irregular menstrual periods, reduced function of the ovaries leading to ovarian failure and infertility
• Mental disability
• Severe infection with bacteria (E coli sepsis)
• Tremors (shaking) and uncontrollable motor functions
• Death (if there is galactose in the diet)

Management

Managing galactosemia involves strict dietary restrictions. The primary treatment is the elimination of galactose and lactose (a sugar derived from galactose) from the diet. Infants with galactosemia should be fed with specialised formulas that do not contain lactose or galactose. As children grow older, they may need to follow a diet that avoids milk, dairy products, and other foods containing lactose or galactose. Consulting a registered dietitian experienced in managing galactosemia is essential to ensure a nutritionally balanced diet.

Treatment

Individuals with galactosemia may require additional medical interventions based on their specific symptoms. For example:

• Newborns with severe symptoms may require intravenous fluids to address dehydration or other complications.
• Individuals with liver disease may require liver transplantation in severe cases.
• Speech therapy, occupational therapy, and special education services can help address developmental delays and learning disabilities.

Symptoms Show Up Later in Life After Treatment

Even if children receive treatment at an early age, delays in learning and development, as well as speech defects, are common. The specific issues may include:

• Learning disabilities
  • Delay in language learning
  • Problems with speech and speech disorders
  • Difficulty with fine and gross motor skills
  • Difficulty with math and reading

• Neurological impairments
  • Problems with gait, balance, and fine motor tremors
  • Inability to coordinate voluntary movements (ataxia)
  • Involuntary muscle contractions (tremors)
  • Inaccurate estimation of distance during muscular activity (dysmetria)

• Ovarian failure
  • Almost all females with severe or classic galactosemia develop premature ovarian insufficiency, in which the ovaries stop releasing eggs earlier than normal.
  • Most females are unable to have children as a result of this premature loss of ovarian function.

Prevention

Galactosemia is an inherited disorder, and currently, there is no known way to prevent its occurrence. Genetic counselling is recommended for couples with a family history of galactosemia or those who have previously had an affected child. Prenatal testing, such as chorionic villus sampling or amniocentesis, can be performed during pregnancy to determine if the fetus has galactosemia. Early diagnosis and management are vital to prevent or minimise the complications associated with galactosemia.

Diet for Galactosemia Patients

What is safe to eat?

The primary treatment for galactosemia is to eliminate all foods containing lactose and galactose from the diet. Consult a physician and a dietitian specializing in metabolic disorders to determine the appropriate modified diet plan for your child.

Typically, children begin eating solid foods between 4 to 6 months of age. For a child on a galactose-restricted diet, safe options include protein-rich foods such as beef, poultry, and eggs, as well as most fruits, vegetables, and grains.”

Calcium supplements

Not consuming milk can make children with galactosemia have low calcium levels. They may have to take calcium supplements every day to help ensure they receive enough calcium. In addition to calcium, vitamin D supplements may also be recommended.

What foods should be avoided?

All foods containing milk and all dairy products, such as cow’s milk, butter, yogurt, cheese or ice cream must definitely be avoided. These children must also avoid any food or drugs that contain casein, curds, whey or whey solids.

When to Contact a Medical Professional?

You must contact a medical professional immediately if an infant with galactosemia experiences any of the following: vomiting, diarrhoea, lethargy, jaundice, failure to thrive, or signs of dehydration like dry mouth or decreased urination. Additionally, seek immediate attention for severe behavioural changes or unresponsiveness. Early intervention is crucial for managing galactosemia and preventing serious complications. 

Frequently Asked Questions