What Is Galactosemia?

What Is Galactosemia?-healthinfi

Galactosemia

Galactosemia, which means galactose in the blood, refers to a group of inherited disorders that impair the body’s ability to process and produce energy from a sugar called galactose. Galactosemia is an inherited disorder that prevents a person from processing the sugar galactose, which is found in many foods. When people with galactosemia inject foods or liquids containing galactose, undigested sugars build up in the blood.

Galactose is present in many foods, including all dairy products (milk and anything made from milk), many baby formulas, and some fruits and vegetables. Galactose is a simple sugar found in milk, cheese, yogurt, and other dairy products. When it’s combined with glucose, it makes lactose.

The impaired ability to process galactose can be due to the deficiency of any of 3 enzymes, caused by mutations in different genes.

Normally when a person consumes a product that contains lactose, the body breaks the lactose down into galactose and glucose. Galactosemia means too much galactose builds up in the blood.

This accumulation of galactose can cause serious complications such as an enlarged liver, kidney failure, and cataracts in the eyes, or brain damage. If untreated, as many as 75% of infants with galactosemia will die.

Duarte galactosemia is a variant of classic galactosemia. Fortunately, the complications associated with classic galactosemia have not been associated with Duarte galactosemia. There is some disagreement over the need for dietary restriction in the treatment of children with Duarte galactosemia. Consult your healthcare professional for his or her advice on this topic.

Galactosemia follows an autosomal recessive mode of inheritance that confers a deficiency in an enzyme responsible for adequate galactose degradation.

Friedrich Goppert (1870–1927), a German physician, first described the disease in 1917, with its cause as a defect in galactose metabolism being identified by a group led by Herman Kalckar in 1956. Galactosemia was the second disorder found to be detectable through newborn screening methods by Robert Guthrie.

Galactosemia affects around 1 in every 60,000 infants of European origin. The condition is caused by a mutation in the gene that codes for the GALT enzyme. In other populations, the incidence rate differs. Galactosaemia is about one hundred times more common (1:480 births) in the Irish Traveller population.

Individuals intolerant to ingested galactose were described as early as 1908, but it wasn’t until 1935 that elimination of galactose from the diet was shown to reverse the acute toxicity syndrome associated with galactosemia.

The Leloir pathway, the main pathway of galactose metabolism, was elucidated in the early 1950s. In 1955, the accumulation of galactose-1-phosphate in red blood cells of infants with impaired galactose metabolism was demonstrated. Methods were subsequently developed to measure galactose-1-phosphate uridyl transferase (GALT) and galactose-1-phosphate in newborn blood spots.

GALT deficiency accounts for about 95% of galactosemias. Although many mutations in the GALT gene have been documented, most cases of GALT deficiency are accounted for by a few high-frequency mutations. In about 5% of cases of galactosemia, the metabolic defect is in galactokinase (GALK), and very rarely, the defect is found to be in uridyl diphosphate galactose epimerase (GALE).

What Is Galactosemia?

Breast milk is full of good things that babies need — key nutrients, hormones, and antibodies that protect them from disease and keep them healthy.

But some babies are born with galactosemia. It’s a rare metabolic condition that prevents them from processing galactose (one of the sugars in breast milk and formula) and turning it into energy. The disorder can cause many problems for newborns and can be life-threatening if left untreated.

It’s easy to test for galactosemia. It’s also simple to treat once it’s diagnosed. And children who have it can live normal lives.

What Causes Galactosemia?

If your baby has classic galactosemia (GALT), the GALT enzyme is either missing or not working correctly. When this enzyme does not work correctly, your baby’s body cannot break down galactose and undigested sugars build up in the blood. This build-up can damage important tissues and organs.

GALT is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for GALT, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with GALT is rare, when both parents are carriers, they can have more than one child with the condition. Learn more about autosomal recessive inheritance.

Galactosemia occurs due to disruptions or changes (mutations) in the GALT gene resulting in a 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.

Galactosemia is hereditary. Both parents must pass it down for their child to get it. If your baby has this condition, it means the genes that produce the enzymes to break down galactose into glucose (a sugar) are missing key parts. Without these parts, the genes can’t tell the enzymes to do their job. This causes galactose to build up in the blood, creating problems, especially for newborns.

Galactosemia is an inherited disorder. This means it is passed down through families. If both parents carry a nonworking copy of the gene that can cause galactosemia, each of their children has a 25% (1 in 4) chance of being affected with it.

There are 3 forms of the disease:

  • Galactose-1 phosphate uridyl transferase (GALT) deficiency: Classic galactosemia, the most common and most severe form
  • Deficiency of galactose kinase (GALK)
  • Deficiency of galactose-6-phosphate epimerase (GALE)

People with galactosemia are unable to fully break down the simple sugar galactose. Galactose makes up one half of lactose, the sugar found in milk.

If an infant with galactosemia is given milk, substances made from galactose build up in the infant’s system. These substances damage the liver, brain, kidneys, and eyes.

People with galactosemia cannot tolerate any form of milk (human or animal). They must be careful about eating other foods containing galactose.

How is galactosemia inherited?

Galactosemia is inherited in an autosomal recessive manner. It affects both boys and girls equally.

Everyone has two copies of the GALT gene that make the GALT enzyme. In children with galactosemia, neither of their GALT genes works correctly. These children inherit one non-working GALT gene from each parent.

Parents of children with galactosemia rarely have the condition themselves. Instead, each parent has a single non-working GALT gene for galactosemia. They are called carriers. Carriers do not have galactosemia because the other GALT gene is working correctly.

When both parents are carriers, there is a 25% chance in each pregnancy for the child to have galactosemia. There is a 50% chance for the child to be a carrier, just like the parents. And, there is a 25% chance for the child to have two working genes.

Genetic counseling is available to families who have children with galactosemia. Genetic counselors can answer your questions about how galactosemia is inherited, choices during future pregnancies, and how to test other family members. Ask your doctor about a referral to a genetic counselor.

Types of Galactosemia

Galactose is converted into glucose by the action of three enzymes, known as the Leloir pathway. There are diseases associated with deficiencies of each of these three enzymes:

There are actually two types of galactosemia, depending on a child’s level of GALT. Children can have classic galactosemia, with a complete or near-complete deficiency of GALT. They may also have partial or variant galactosemia, with a partial GALT deficiency.

Unlike infants with classic galactosemia, infants with variant galactosemia, including the Duarte variant, usually don’t have any symptoms.

There are 3 main types of galactosemia which are distinguished based on their genetic causes, signs and symptoms, and severity.

Classic galactosemia (type 1) –

The most common and severe type, caused by mutations in the GALT gene, and characterized by a complete deficiency of an enzyme called galactose-1-phosphate uridyl transferase (GALT). Early signs and symptoms include liver dysfunction, susceptibility to infections, failure to thrive, and cataracts. These can usually be prevented or improved by early diagnosis and treatment, but other progressive or long-term problems are common despite treatment. These include intellectual deficits, movement disorders, and premature ovarian failure (in females).

Galactokinase deficiency (type 2)

Caused by mutations in the GALK1 gene and characterized by a deficiency of the enzyme galactokinase 1. This type typically causes only the development of cataracts, which may be prevented or resolved with treatment. Rarely, this type causes pseudotumor cerebri (a condition that mimics the symptoms of a large brain tumor when no brain tumor is present).

Galactose epimerase deficiency (type 3) –

Caused by mutations in the GALE gene and characterized by a deficiency of the enzyme UDP-galactose-4-epimerase. Symptoms and severity of this type depend on whether the deficiency is confined to certain types of blood cells or is present in all tissues. Some people with this type have no signs or symptoms, while others have symptoms similar to those with classic galactosemia. Like in classic galactosemia, many symptoms can be prevented or improved with treatment.

There is also a “variant” of classic galactosemia called Duarte variant galactosemia, in which a person has mutations in the GALT gene but has only partial deficiency of the enzyme. Infants with this form may have jaundice, which resolves when switched to a low-galactose formula.

Some studies have found that people with this form are at increased risk for mild neurodevelopmental problems, but other studies have found there is no increased risk. The risk may depend on the extent of the deficiency.

Inheritance of all types of galactosemia is autosomal recessive. The diagnosis may be suspected based on symptoms or results of newborn screening tests and can be confirmed by measuring enzyme activity and genetic testing. Depending on the type of galactosemia, treatment may involve removing galactose from the diet (as soon as the disorder is suspected), calcium supplementation, and individualized care for any additional symptoms. The long-term outlook for people with galactosemia varies depending on the type, symptoms present, and commitment to the diet.

Symptoms of galactosemia are:

If your newborn has classic galactosemia, it’ll appear normal at birth. Symptoms start to show up within a few days after they begin to drink breast milk or formula with lactose the milk sugar that contains galactose.

Your baby first loses its appetite and starts vomiting. Then they get jaundice, a yellowing of the skin and the whites of their eyes. Diarrhea is common, too. The disease leads to severe weight loss and your baby struggles to grow and thrive.

Without treatment, over time your child may develop cataracts and can be susceptible to infections. They may have liver damage and kidney problems. Their brain may not mature well. That can cause developmental disabilities. Some children have issues with their motor skills and muscles. For girls, it can cause their ovaries to stop working. Most with this condition can’t have children.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO).

The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Infants with galactosemia can show symptoms in the first few days of life if they eat formula or breast milk that contains lactose. The symptoms may be due to a serious blood infection with the bacteria E Coli.

Symptoms of galactosemia are:

  • Convulsions
  • Irritability
  • Lethargy
  • Poor feeding — baby refuses to eat formula containing milk
  • Poor weight gain
  • Yellow skin and whites of the eyes (jaundice)
  • Vomiting

Symptoms of galactosemia usually develop several days or weeks after birth. The most common symptoms include:

  • loss of appetite
  • vomiting
  • jaundice, which is yellowing of the skin and other parts of the body
  • liver enlargement
  • liver damage
  • fluid building up in the abdomen and swelling
  • abnormal bleeding
  • diarrhea
  • irritability
  • fatigue or lethargy
  • weight loss
  • weakness
  • higher risk of infection

Babies who have galactosemia have problems eating and tend to lose weight. This is also known as failure to thrive. Learn more about what failure to thrive means for your child.

Diagnosis Of Galactosemia

Galactosemia is usually diagnosed through tests that are done as part of newborn screening programs. A blood test will detect high levels of galactose and low levels of enzyme activity. The blood is usually taken by pricking a baby’s heel.

Most children with galactosemia are diagnosed before they develop many galactosemia symptoms because the condition is picked up on newborn screening tests that are done when the child is born. All 50 states in the U.S. test newborns for galactosemia.

If galactosemia is suspected based on a newborn screening test, confirmatory testing for levels of galactose-1-phosphate (gal-1-p) and GALT will be done. If the infant has galactosemia, gal-1-p will be high and GALT will be very low.

Classic galactosemia and clinical variant galactosemia are diagnosed when galactose-1-phosphate is elevated in red blood cells and GALT enzyme activity is reduced. Molecular genetic testing is also available to identify mutations in the GALT gene.

Nearly 100% of infants with galactosemia can be diagnosed in newborn screening programs using a blood sample from the heel stick. Infants with clinical variant galactosemia can be missed at newborn screening if GALT enzyme activity is not measured.

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

A urine test may also be used to diagnose this condition. Genetic testing can also help diagnose galactosemia.

Galactosemia may also be diagnosed prenatally using chorionic villus biopsy or amniocentesis tests. Children who are not diagnosed by newborn screening tests and are having symptoms might be suspected of having galactosemia if they have something known as “reducing substances” in their urine.

Prenatal tests can be performed to check for galactosemia as early as in the 15th to 16th week of pregnancy. The condition is usually first detected through a heel prick test performed 72 hours after birth as part of newborn screening.

The condition is managed by feeding infants on a diet that is lactose and galactose free. This helps to prevent complications such as liver and kidney damage, although some individuals still go on to develop long-term complications.

Exams and Tests

Signs include:

Test results may show:

  • Amino acids in the urine or blood plasma
  • Enlarged liver
  • Fluid in the abdomen
  • Low blood sugar

Newborn screening in many states will test for this condition.

Tests include:

  • Blood culture for bacterial infection (E. coli sepsis)
  • Enzyme activity in the red blood cells
  • Ketones in the urine
  • Prenatal diagnosis by directly measuring the enzyme galactose-1-phosphate uridyl transferees
  • “Reducing substances” in the infant’s urine, and normal or low blood sugar while the infant is being fed breast milk or a formula containing lactose

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Newborn Screening

  • The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.

Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can’t travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

  • To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist.

Risk Factors Of Galactosemia

The primary risk factor is having parents who carry the gene for galactosemia.

Treatment 

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.

Immediate exclusion of dietary galactose (breastfeeding, cow’s milk) should be instituted at the first suspicion of galactosemia. Infant soy formulas are recommended unless there is significant liver disease. For the newborn who is seriously ill at the time of diagnosis, supportive care may include treatment with vitamin K and fresh-frozen plasma to correct clotting abnormalities. Gram-negative sepsis should be assumed and appropriate IV antibiotics are given.

Because the diagnosis and therapy of this disorder are complex, the pediatrician is advised to manage the patient in close collaboration with a consulting pediatric metabolic disease specialist. It is recommended that parents travel with a letter of treatment guidelines from the patient’s physician.

A lactose tolerance test should NOT be administered to children with galactosemia. Fortunately, the body of an infant 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.

People with this condition must avoid all milk, products that contain milk (including dry milk), and other foods that contain galactose, for life. Read product labels to make sure you or your child with the condition are not eating foods that contain galactose.

Infants can be fed:

  • Soy formula
  • Another lactose-free formula
  • Meat-based formula or Nutramigen (a protein hydrolysate formula)

Calcium supplements are recommended.

Genetic counseling and hormone replacement therapy may also be recommended. Galactosemia can affect puberty, so hormone replacement therapy may help.

It’s important to talk to your doctor and address concerns early.

The following are treatments often advised for children with classic galactosemia:

Lactose and galactose-free diet 

People with classic galactosemia are encouraged to follow lactose and galactose-free food plan throughout life.  Lactose or galactose are found in the following foods, all of which must be avoided:

  • Milk and all dairy products
  • Processed and pre-packaged foods often contain lactose
  • Tomato sauces
  • Some candies
  • Certain medications – tablets, capsules, sweetened liquid drops that contain lactose as a filler
  • Some fruits and vegetables also contain galactose
  • Any foods or drugs which contain the ingredients lactulose, casein, caseinate, lactalbumin, curds, whey, or whey solids
  • other dairy products

Your dietitian will help you develop a food plan that allows your child to avoid lactose and galactose while still eating the right amount of protein, nutrients, and energy to keep him or her healthy.

Your child’s food plan will depend on many things such as his or her age, weight, general health, and blood test results. Your dietician will fine-tune your child’s diet over time. The special food plan should be continued throughout life.

Calcium supplements 

Since children with galactosemia are not eating milk products, calcium intake may be too low. This may cause their bones to be weaker than average (osteopenia). Therefore, children with galactosemia are often advised to take calcium supplements to ensure they receive enough calcium each day.

Some doctors also advise Vitamin D and Vitamin K supplements in addition to calcium.

Your doctor will tell you what supplements to give your child and how much.  Do not use any medication or supplement without checking with your doctor.

Special lactose-free formula

Newborns with galactosemia are given a special formula free of lactose.  The most common formulas used for babies with galactosemia are those made with soy protein isolate. Soy milk itself contains galactose and should not be used.

Your metabolic doctor and dietitian will tell you what type of formula is best and how much to use. Some states offer help with payment for this formula and others require private insurance coverage for the formula and other special medical foods.

Informing friends, relatives, teachers, and child-care providers

It is important for you to tell everyone who helps care for your child that he or she cannot eat or drink milk-containing foods.  A Medic-Alert bracelet that states your child’s food restrictions can be helpful.  In addition, your doctor may advise you to carry an emergency treatment letter with steps for your child’s care.

Monitoring health

Babies and young children with galactosemia usually need regular blood and urine tests.  These tests are used to detect toxic substances made when galactosemia is not in good control.  The test results will help your doctors and dietitian fine-tune the treatment to meet your child’s needs.

Your doctor may also suggest a formal evaluation of your child’s mental development and his or her speech and language skills.  If your child shows delays in certain areas of learning or speech, extra help can be arranged.  Early intervention programs are available in most states to provide services before children reach school age.

Monitoring for other health problems associated with galactosemia such as cataracts, bone problems, and premature ovarian failure may also be done.

You can replace many of these foods with dairy-free alternatives, like almond or soy milk, sorbet, or coconut oil. Learn about almond milk for babies and toddlers.

Human breast milk also contains lactose and isn’t recommended for babies diagnosed with this condition. Some babies with Duarte variant galactosemia may still be able Trusted Source to drink breast milk, however. Talk to your doctor if you have any concerns about not being able to breastfeed your baby.

While the Centers for Disease Control and Prevention (CDC) recommends Trusted Source breast milk as the best way for infants to receive nutrients, they don’t recommend breastfeeding an infant with galactosemia. Instead, you’ll need to use a lactose-free formula. Ask your doctor about formula options.

If you plan to use formula, look for a lactose-free version. Many dairy products are fortified with vitamin D. Talk to your doctor about vitamin D supplements and whether they are appropriate for your child.

Outlook

Galactosemia is a rare inherited disorder that affects how galactose is processed in the body. If galactosemia isn’t diagnosed at an early age, then complications can be serious.

Following a low-galactose diet is an essential part of managing this disorder. Talk to your doctor about additional diet restrictions and other concerns.

Can you test during a future pregnancy?

If both gene changes (variants) have been found in your child with galactosemia, DNA testing can be done during any future pregnancies. If DNA testing is not helpful, an enzyme test using cells from the fetus can be done during pregnancy. The sample needed for this test is obtained by either CVS or amniocentesis.

Parents may choose to have testing during pregnancy or wait until birth to have the baby tested. Parents may also choose to use assisted reproductive techniques to decrease the chance that their future children would have galactosemia. A genetic counselor can talk to you about your choices and answer questions about prenatal testing or testing your baby after birth.

If you do not have a prenatal diagnosis during your next pregnancies, you should feed your newborn with the recommended formulas instead of breast milk or regular formula until the results of newborn screening or additional diagnostic tests have been completed.

Who is at risk for galactosemia?

The gene defect for Galactosemia is a recessive genetic trait. This faulty gene only emerges when two carriers have children together and pass it to their offspring. For each pregnancy of two such carriers, there is a 25% chance that the child will be born with the disease and a 50% chance that the child will be a carrier for the gene defect.

What are the Possible Complications?

These complications can develop:

  • Cataracts
  • Cirrhosis of the liver
  • Delayed speech development
  • Irregular menstrual periods, reduced function of 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)

Newborn

  • Liver failure
  • Kidney problems
  • Sepsis
  • Brain edema
  • Pseudotumor cerebri
  • Feeding difficulties
  • Growth problems
  • Cataracts

Infants/Toddlers

  • Speech/ language delays
  • Coordination problems (fine and gross motor skills)
  • Developmental delays
  • Attention issues
  • Growth problems
  • Cataracts

Young Children

  • Learning delays
  • Issues with fine and gross motor skills (e.g., handwriting)
  • Growth problems
  • Speech/ language problems
  • Behavioral and emotional issues
  • Tremor

Teen

  • Puberty and fertility problems (females)
  • Growth delays
  • Anxiety
  • Social problems
  • Learning difficulties
  • Tremor

Adult

  • Tremor
  • Seizures
  • Anxiety
  • Depression
  • Attention Deficit Hyperactivity Disorder (ADHD)
  • Cataracts

Premature ovarian insufficiency is only seen in women. The ovaries stop functioning at an early age and affect fertility. This usually occurs before the age of 40. Some of the symptoms of premature ovarian insufficiency are similar to menopause.

When to Contact a Medical Professional

Call your health care provider if:

  • Your infant has galactosemia symptoms
  • You have a family history of galactosemia and are considering having children

Prevention

It is helpful to know your family history. If you have a family history of galactosemia and want to have children, genetic counseling will help you make decisions about pregnancy and prenatal testing. Once the diagnosis of galactosemia is made, genetic counseling is recommended for other members of the family.

Many states screen all newborns for galactosemia. If the newborn test shows possible galactosemia, they should stop giving their infant milk products right away and ask their provider about having blood tests that can be done to confirm a diagnosis of galactosemia.

Questions to Ask Your Doctor

  • Which type of Galactosemia do I have? Type I? Type II? Or Type III?
  • What kinds of testing do I need to have?
  • Do other members of my family need to be tested?
  • What kinds of foods should I be eating?
  • Is it possible to be connected to a dietitian or someone who can assist with meal planning?
  • Do all my symptoms correspond with galactosemia or is it possible to have other kinds of GI or liver-related problems?
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