Galactosemia

At Boston Children’s Hospital, we have helped many infants and families who have been affected by galactosemia, a rare genetic metabolic disorder in which babies are born without the ability to convert the milk sugar, galactose, into glucose (the form of sugar used by the body for energy).

Here are the basics of galactosemia:

• Galactosemia affects 1 in every 40,000 to 1 in 60,000 newborns around the world.
• Galactosemia is one of the metabolic diseases that can be identified through Newborn Screening Evaluation. Every state in the United States has or has access to a newborn screening program and is mandated by law to screen for galactosemia.
• Initial signs usually present in the first few weeks of life and include refusal to feed, vomiting, lethargy, jaundice, cataracts, and sepsis (infection).
• Babies born with galactosemia need to be put on a special lactose-free diet shortly after birth in order to prevent serious multiorgan involvement including death. If treatment is started after the first 10 days of life, it is believed that the majority of infants with severe or classic galactosemia will die because of a generalized infection. If they do survive the first month of life untreated, they are likely to develop cirrhosis.

Three types of galactosemia have been identified. They are caused by a mutation in the GALE, GALK1, and GALT genes. These three genes are responsible for making all of the enzymes that are essential for breaking down (metabolizing) galactose. Almost all of the patients with galactosemia have the classic or life-threatening form of the disease due to severe GALT deficiency.

For our purposes, the information will only focus on classic galactosemia, the most common type of galactosemia that result from mutations in the GALT gene.

• The variant Duarte galactosemia, a much milder form of galactosemia, also involves a mutation in the GALT gene. Whereas classic galactosemia completely prevents the normal processing of galactose, the Duarte variant only reduces enzyme activity by about 75%, but not by 100% as in classic galactosemia. Children with Duarte galactosemia usually do not have serious health effects and may or may not need treatment.

Other types of classic galactosemia, far rarer, that are not discussed here include:

• Galactosemia type II, caused by results from mutations in the GALK1 gene
• Galactosemia type III, caused by mutations in the GALE gene

Classic galactosemia occurs when an enzyme called galactose-1-phosphate uridyltransferase (GALT) is missing or not functional. This liver enzyme is responsible for breaking down galactose (a sugar byproduct of lactose found in breast milk, cow’s milk, and other dairy foods) into glucose. When galactose cannot be changed to glucose, it, as well as its byproducts such as galactose-1-phosphate, builds up in tissues and blood and affects many parts of the body.

This hereditary condition is passed from parent to child as an autosomal recessive disease. This means that a child needs to inherit two copies of the defective gene (one from each parent) in order to have the disease.

A baby may develop signs of galactosemia within the first few days of life if they consume lactose found in breast milk or baby formula.

These initial signs include:

• Refusal to eat
• Spitting up or vomiting
• Yellowing of the skin (jaundice)
• Lethargy
• Cataracts

Even if children receive treatment at an early age, delays in learning and development, as well as speech defects, are common. The specific issues and level of delay varies from child to child, but may include:

• Learning disabilities
  • Delay in language acquisition
  • Problems with speech are common; the majority of children with classic galactosemia have speech disorders
  • Difficulty with fine and gross motor skills
  • Difficulty with math and reading
• Neurological impairments
  • Problems with gait, balance, fine motor tremors affecting (affecting a minority of children and adults).
  • 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 (POI, a condition in which the ovaries stop releasing eggs earlier than normal).
  • Although the exact cause is not known, it is believed that galactose or its byproduct may be toxic to the ovaries. Most females are unable to have children as a result of this premature loss of ovarian function, which resembles early menopause.

Diagnosis for galactosemia is based on a comprehensive review of medical and family history, physical evaluation, and specific biochemical testing. In addition, we have, in concert with the New England Newborn Screening Program, one of the best newborn screening programs in the world. All infants born in New England will be tested on day 2 of life for galactosemia.

In addition, under the Newborn Screening Program, every baby born in New England is tested for more than 30 genetic, endocrine, and metabolic disorders. 

Newborn screening evaluation

Metabolic disorders such as galactosemia can often be a challenge to diagnose since the physical signs of disease may not be present at birth. Newborn screening is a testing procedure that was developed to identify these kinds of diseases in newborns. This screening test is important because the earlier these disorders are identified, the less likely a child will have long-term problems or irreversible complications. Unfortunately, this is not always the case with galactosemia.

• Before leaving the hospital after birth, a small sample of blood is taken from the baby’s heel. This blood sample is put on a special piece of paper and sent to the New England Newborn Screening Program for analysis. If the test results are positive, the baby will be sent to the proper treatment center.
• Babies who test positive in New England may be sent to the Metabolism Program at Boston Children’s Hospital. To confirm the diagnosis, we obtain a fresh sample of blood and a urine specimen and send them to our metabolic laboratory. Because untreated infants may die in the first two weeks of life, we will begin diet therapy even before a positive diagnosis is confirmed.
• Although screening tests are mandatory in all states, not all states screen for the same disorders. To find a comprehensive list of what disorders your state screens for, visit the National Newborn and Genetics Resource Center.

Genetic testing

Genetic testing for galactosemia can be performed on a CVS or amniotic fluid sample. This test evaluates the likeliness that the disorder is present in a fetus. Genetic testing is employed after birth to determine the exact type of GALT gene mutation in an infant who has a confirmed GALT enzyme deficiency.

Diet

The only treatment for galactosemia is avoiding foods that contain lactose and galactose.

A physician and a dietitian who specializes in metabolic disorders can tell you what modified dietary plan your child will need to follow.

What foods should be avoided?

A person with galactosemia must avoid foods containing milk and all dairy products, such as:

• Cow's milk
• Butter
• Yogurt
• Cheese
• Ice cream

Any foods or drugs which contain the following ingredients should also be avoided during infancy:

• Casein
• Curds
• Whey
• Whey solids

What foods are safe to eat?

A child can start eating solid foods at around 4 to 6 months of age. A child on a galactose-restricted diet can eat most foods containing protein, such as beef, poultry, and eggs. They can also eat most types of fruits, vegetables, and grains.

Calcium supplements

Since children with galactosemia cannot consume milk products, their calcium levels may be too low. Taking calcium supplements every day will help ensure they receive enough calcium. Vitamin D supplements may be recommended in addition to calcium.

Your child's doctor will tell you what supplements to give your child and how much. Do not use any medication or supplement without checking first with the clinician on your child's medical team.

Therapy

Different types of therapy can also be used to address your child's unique social, behavioral, communication, and academic needs.

• Speech therapy can help improve your child's communication skills.
• Targeted educational sessions may be employed to overcome learning difficulties in specific areas of need.
• Physical therapy can increase mobility and muscle strength and help your child to work within his functional limitations.
• Behavioral therapy is an important resource that focuses on managing emotional and behavioral problems. This therapy can also teach families how help a child with galactosemia cope with the anxiety and frustration of following such a restricted diet.

The Metabolism Program at Boston Children's Hospital provides comprehensive evaluation and treatment for infants, children, and adolescents who have diseases that involve metabolism. We also see adults who have been previously diagnosed with a metabolic disorder.

Our program is staffed by a team of experienced clinicians, all of whom have specialized training in the care of individuals with metabolic diseases. Experts from Metabolism, Neurology, Gastroenterology, Nutrition, Ophthalmology, social work, and Psychology work together to perform comprehensive and accurate neuroimaging, ocular assessments, neuropsychological studies, and other specialized evaluations.

Our multidisciplinary approach works to enhance a child’s health and development and helps them reach their maximum potential in all aspects of their normal activities.