What is Galactosemia?
Galactosemia means "galactose in the blood." It is an inherited condition in which people have trouble digesting a type of sugar called galactose found in small amounts in the food they eat. Galactose is found in all dairy products, in most baby formulas, and some fruits and vegetables. It is part of a larger sugar called lactose 1.
Researchers discovered galactosemia very early in the 20th Century, but the defective gene that caused it wasn't found until 1956. Another significant advancement took place in 1963 when the condition was first found to be detectable through a newborn screening method.
What's in this Guide?
- What is Galactosemia?
- How is Galactosemia Different from Lactose Intolerance?
- Signs & Symptoms of Galactosemia
- Causes and the Genetic Pattern of Galactosemia
- How Common is Galactosemia? - Affected Populations
- Diagnosis of Galactosemia
- Treatment & Management of Galactosemia
- Prognosis of Galactosemia
- What to do Next: Living with Galactosemia
Disclaimer: Before You Read
It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.
Genetics is a quickly changing topic. Read More...
Because a person cannot digest galactose properly, it builds up in their blood and interferes with the body’s ability to process and produce energy. That can lead to several health problems.
The inability to process galactose is due to the genetic deficiency of three enzymes that are caused by mutations in different genes. Three main types of galactosemia are differentiated by their genetic causes, signs, symptoms, and severity.
Also known as classic galactosemia, Galactosemia Type I, or galactose-1 phosphate uridylyltransferase deficiency, it is the most common and severe form of this disease. It is caused by mutations in the GALT gene.
The GALT gene provides instructions to the enzyme called galactose-1-phosphate uridylyltransferase. This enzyme helps the body break down galactose so that it can be converted to glucose, which is the primary energy source for most of the body's cells.
Another form of galactose is also produced that is used to build proteins and fats. These modified proteins and fats play are essential in building cellular structures and transporting molecules. They also play vital roles in producing energy and in chemical signaling. 2.
If affected infants aren't treated within a few days after birth with a low-galactose diet, life-threatening complications can appear. This includes lethargy, difficulty feeding, jaundice, liver damage, abnormal bleeding, sepsis, shock, and other serious conditions, up to and including death.
Even when treatment begins immediately, other long-term problems affecting movement and mental impairments are common.
There is also a variant of GALT deficiency called Duarte variant galactosemia, sometimes referred to as Duarte galactosemia or DG. It is more common that GALT deficiency.
A person affected by this condition has a mutation of the GALT gene, but there is only a partial deficiency present in the enzyme.
Instead of carrying severe mutations in both copies of their GALT gene, patients with Duarte variant galactosemia carry one GALT gene with a severe mutation and a second GALT gene that is only very mildly impaired.
This generally means a child has one parent who is a carrier with a severe GALT mutation, and one parent who is a carrier for the Duarte variant.
In most cases, patients with Duarte variant galactosemia have approximately 25 percent of normal red blood cell GALT activity. People with classic galactosemia usually indicate less than 1% of the normal level of GALT activity in red blood cells 3.
Infants with the Duarte form may have jaundice, which is resolved when switched to a low-galactose formula. Some studies show people with this form are at increased risk for mild neurodevelopmental problems. Still, the amount of risk of this developing may depend on the extent of the deficiency.
Caused by a mutation in the GALK1 gene, this form of galactosemia is also known as Galactosemia Type II, galactose kinase, or galactokinase deficiency.
GALK deficiency causes fewer medical problems than Type I and is characterized by different types of signs and symptoms. However, like GALT deficiency, patients with GALK deficiency can’t fully metabolize galactose either.
GALK deficiency is caused by a defect in the enzyme galactokinase 1. This type typically only causes the development of cataracts that can be prevented or resolved with treatment.
In a few rare cases, Type II may cause pseudotumor cerebri. This condition mimics the symptoms of a large brain tumor, but in actuality, no brain tumor is present. Also, although research is limited, it does appear that there may be a higher incidence of mental retardation with this form of the disease.
Overall, GALK deficiency is extremely rare and may or may not be detected by newborn screening programs. A newborn screening must be specifically designed to detect GALK deficiency.
Receiving a “normal” newborn screening result for galactosemia can’t always rule out a diagnosis of galactokinase deficiency.
A mutation in the GALE gene causes this condition, sometimes referred to as Galactosemia Type III or deficiency of galactose-6-phosphate epimerase. A deficiency of the enzyme UDP-galactose-4-epimerase characterizes type III.
The degree of the symptoms and severity of GALE deficiency depends on whether or not the deficiency is present only in some types of white blood cells or is found in all tissues.
As a result, some people with GALE deficiency show no symptoms at all, while others exhibit many of the same signs and symptoms of people with classic galactosemia.
For diagnostic purposes, patients with impaired GALE activity are categorized as having one of three forms of the deficiency:
- generalized GALE deficiency that results from profound but not complete loss of GALE activity
- intermediate GALE deficiency that results from partial but not profound loss of epimerase activity in multiple tissues
- peripheral GALE deficiency that results from loss of epimerase activity in some cell types (e.g., red blood cells) but not in others (e.g., lymphoblasts or liver).
Generalized GALE deficiency is extremely rare. Other forms of GALE deficiency are more common, especially in certain populations.
How is Galactosemia Different from Lactose Intolerance?
Galactosemia does sound a lot like lactose intolerance, but there is a big difference between the two conditions. The most obvious is:
Galactosemia is life threatening. Lactose intolerance is not.
Galactosemia is caused by a genetic mutation that inhibits the body's ability to produce a functional enzyme needed to metabolize galactose sugars fully.
When the body can't process the sugars, they remain in the bloodstream, and this can lead to serious and life-threatening conditions, as well as long-term damage.
There are currently no treatments that allow a person with galactosemia to eat an unrestricted diet, without concern of developing complications 4.
Lactose intolerance is the body’s inability to digest significant amounts of lactose. It is often the result of a shortage of Beta Galactosidase (Lactase) enzyme.
This enzyme is usually produced by cells that line the small intestine. When this digestive enzyme is not present, lactose molecules can't be split into glucose and galactose, so it cannot be absorbed.
When lactase is limited, a person can develop intestinal gas, bloating, and diarrhea. Typically, there are no other acute or chronic complications.
Lactose passes through to the large intestine and is either broken down by bacterial flora or excreted unchanged.
Some people with lactose intolerance can tolerate limited amounts of lactose in their diet because they have some lactase activity and can safely do so without complication 5.
Others use Lactaid and Dairy Ease (Lactase) enzymes that are taken orally. These options are not available in Galactosemia.
Signs & Symptoms of Galactosemia
Signs and symptoms of galactosemia can appear in the first few days of life if an infant eat formula or breast milk that contains lactose.
Symptoms may occur due to a severe E coli blood infection and will include:
- Lethargy and tiredness
- Poor weight gain
- Baby refuses to eat formula containing milk
- Sleeping longer or more often
- Low blood sugar (hypoglycemia)
As individuals grow older, they may exhibit a variety of other symptoms. But not all people with galactosemia will have all the following symptoms:
- Cognitive impairment
- Failure to thrive in infancy
- Faltering weight in infancy
- Feeding difficulties in infancy
- Global developmental delay
- Hepatic failure (liver failure)
- Intellectual disability
- Nausea and vomiting
- Abnormal blood clotting
- Voice abnormalities
- Ascites (accumulation of fluid in the abdomen
- Hepatomegaly (enlarged liver)
- Muscular hypotonia (weak or low muscle tone)
- Sepsis (infection in the bloodstream
- Fluid accumulation in lower limbs
- Difficulty articulating speech (dysarthria)
- Microcephaly (abnormally small skull)
- Renal failure
- Impaired vision
- Speech apraxia
Causes and the Genetic Pattern of Galactosemia
Mutations in the GALT, GALK1, and GALE genes cause galactosemia. When these genes mutate, they virtually eliminate the ability to provide instructions that make the enzymes that are essential for processing galactose in a person's diet. When galactose and related compounds build up in the body, it leads to toxic conditions that damage tissues and organs.
A variation of a GALT gene mutation reduces, but does not eliminate, the ability to produce this enzyme and is known as a Duarte variation. The symptoms of this variation are milder than with classic galactosemia.
Galactosemia is inherited in an autosomal recessive pattern 6. That means both copies of a gene (one from the mother and the father) each have cell mutations. In other words, children inherit one non-working gene for the condition from each parent.
The parents of a person with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of galactosemia.
Parents with a single non-working gene are called carriers. Carriers do not have galactosemia, but the other gene of this pair works correctly.
When both parents are carriers, a 25% chance exists 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 a 25% chance for the child to have two working genes.
For people with a history of galactosemia in their family, genetic counseling and testing may be a viable option as part of a larger overall family planning effort.
Genetic counselors can answer questions about how galactosemia is inherited, why types of choices you have, and if testing of other family members is warranted.
How Common is Galactosemia? - Affected Populations
Classic galactosemia occurs in 1 in 30,000 to 60,000 newborns worldwide in all ethnic groups 7. However, it appears to be slightly more common in people from Ireland, where 1 in 24,000 Irish babies are born with this condition.
GALT and GALE deficiencies are less common. It's estimated that GALT deficiency affects less than 1 in 100,000 babies. GALE deficiency is very rare, with no viable statistics to track the frequency.
Diagnosis of Galactosemia
Galactosemia is diagnosed as part of newborn screening in many states. If the newborn test indicates galactosemia, parents should stop giving their infant milk products immediately and seek blood tests to confirm a galactosemia diagnosis.
In other instances, a newborn may be diagnosed if they start presenting symptoms of the condition shortly after birth.
In all cases, it’s helpful to know your family’s medical history and if there are any instances of galactosemia that have occurred. If the condition is a part of your family history, then testing may be wise and also indicated for other members of the family.
Prenatal DNA testing can be done during future pregnancies. Either CVS or amniocentesis obtains a sample needed for this test.
Specific tests to check for galactosemia include 8:
- 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 transferase
Test results may show an enlarged liver, fluid in the abdomen, low blood sugar, or amino acids in the blood or urine.
A GALT test that produces an out-of-range result does not necessarily mean that a child has galactosemia. An out-of-range result may take place because an initial blood sample was too small, or the test was performed too early. Be sure to get confirmatory tests if this happens.
Treatment & Management of Galactosemia
When a newborn is diagnosed, treatment should start within the first ten days of life to minimize health impacts.
Individuals with galactosemia must avoid all milk and products that contain milk, for life. That also includes dry milk and other foods that contain lactose and galactose. It's critical to monitor food intake by reading food labels to make sure anyone with the condition does not accidentally ingest these food products.
Infants and children who are missing the GALT enzyme completely or who have less than 10% of the usual amount of the enzyme must follow a strict dietary regimen 9.
Specifically, avoid the following foods which contain lactose or galactose 10:
- Milk and all dairy products
- Processed and pre-packaged foods often contain lactose
- Tomato sauces
- Some candies
- Some medications in the form of tablets, capsules, sweetened liquid drops, can contain lactose as a filler
- Some fruits and vegetables may contain galactose
- Any foods or drugs that contain lactulose, casein, caseinate, lactalbumin, curds, whey, or whey solids.
Instead, infants can be fed soy formula (soy milk contains galactose and should not be used), other lactose-free formulas, or meat-based formula or Nutramigen (a protein hydrolysate formula). Calcium supplements are recommended.
Part of the treatment and management of any form of galactosemia should include working with a metabolic doctor or a dietician who is familiar with this condition.
A dietitian will help develop a food plan that allows a child to avoid lactose and galactose while still eating the right amount of protein, nutrients, and energy to keep him or her healthy.
This food plan will depend on several variables, such as age, weight, general health, and blood test results. The dietician will fine-tune the diet and food plan over time, and it will need to be continued throughout life.
Because a child is not able to ingest milk or milk products, their overall calcium intake may be too low. As a result, doctors often prescribe calcium supplements.
Calcium, Vitamin D and Vitamin K may also be prescribed by some medical professionals. Do use any medication or supplement without first checking with your doctor.
Once diagnosed, immediate treatment is a priority to prevent serious health problems and longer-term intellectual disabilities. Infants with galactosemia who are not treated shortly after birth can develop permanent effects.
Part of the treatment also includes regular blood and urine tests. These are administered to detect levels of toxic substances that may build up inside the body. The results are also used to fine-tune diet and treatment protocols.
Doctors may also suggest a formal evaluation of a child's mental development, speech, and language skills. Early detection of deficiencies in these areas makes it easier to arrange for treatment.
Also, it's critical to let anyone who cares for your child about their condition. That includes caregivers, school officials, relatives, and friends.
It may be advisable to have the child wear a medical alert bracelet and for parents to carry an emergency medical care letter from their doctor with steps on how to care for a child in various situations.
Even when treatment takes place at an early age, complications can still develop in many cases.
Parents need to understand that treatment does not provide a cure for galactosemia. The condition must be managed as effectively as possible to avoid serious long-term complications. Even so, there are no guarantees that serious complications will not develop.
Some children with classic galactosemia experience delays in learning and development that will require extra help when they reach school age. The level of delay varies from child to child.
Some children develop speech and language delays, while others have delays in motor skills such as walking and coordination and balance 11. Learning disabilities can be challenging to diagnose because some children naturally develop at a slower rate simply due to their level of maturity.
Neurological impairments (fine motor difficulties) can sometimes appear to be a learning disability. For example, a child who has trouble writing numerals or pointing may appear to have a learning disability as it relates to arithmetic.
But this may simply because he or she can't control their writing well enough to demonstrate that they have mastered the concept. In other cases, the child may have both problems.
Even when carefully treated, girls with galactosemia have a higher chance of having delayed periods and premature ovarian failure resulting in infertility.
Severe bacterial infections may also develop (E coli sepsis).
Some untreated babies have high levels of ammonia in their blood. High ammonia levels and hypoglycemia can both lead to coma and death.
Many children also develop cataracts, so regular visits every 3-4 months with an ophthalmologist are recommended as well. Cataracts are mostly observed in newborns but can also occur in adults.
It's estimated that 10-30% of newborns with classic galactosemia may develop cataracts in the first few weeks of life. When an effective diet is implemented, cataracts usually clear up on their own, but surgery is sometimes necessary.
Cirrhosis of the liver may also be another complication for some patients. Left untreated, children eventually die of liver failure.
Prognosis of Galactosemia
People who are diagnosed early and follow a strict diet can lead a relatively normal life with a normal life expectancy.
However, there are no guarantees that some symptoms or long-term impacts may or may not develop over time, even in those who avoid galactose in all its forms.
What to do Next: Living with Galactosemia
Support groups and organizations that advocate for galactosemia can provide valuable resources and insights to help you and your family best manage this condition:
Baby’s First Test
Registries for Galactosemia:
Galactosemia Patient Registry
GeneReviews has information on classic galactosemia.
The Screening, Technology And Research in Genetics (STAR-G) Project has more information on GALT.
Galactosemic Families of Minnesota (GFMN) - Minnesota, US Support Group
Galactosemia Families of the Southern States (GFSS) - Texas and surrounding states, USA Support Group - contact Jo Beth Southard.
Galactosaemia Support Group (GSG) - UK Patient Support Group
European Galactosaemia Society (EGS) - Europe Patient Support Group
The Australian Galactosaemia Support Network (AGSN) - Australia Patient Support Group
- GALK1 gene.
- GALE gene.
- Galactosemia. GeneAware. Retrieved online, December 2019.
- Classic Galactosemia. Baby's First Test. Retrieved Online, December 2019.
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