GALACTOSEMIA (GALACTOSE INTOLERANCE): CAUSES, SYMPTOMS, TREATMENT
Medically Reviewed by Dr. Rosmy Barrios
Galactosemia is a rare hereditary condition that impacts the body's capacity to process galactose, a sugar found in milk and dairy products, as well as some fruits and vegetables.
Galactose is a simple sugar, also known as a monosaccharide. It is found primarily in lactose, the sugar in milk and dairy products[1]. Our bodies can convert galactose into glucose[2], the primary fuel our cells use for energy. Galactose forms specific fats and sugars important for brain development, especially during infancy.
People with galactosemia lack the enzyme needed to break down galactose into glucose. When someone with galactosemia consumes galactose, it builds up in the body and becomes toxic, causing damage to various organs, particularly the liver, eyes, and brain. This condition can result in severe health complications if left untreated.
Classic galactosemia affects about 1 in 40,000-60,000 newborns[3]. It is an autosomal recessive condition, which means that to develop the disorder, a child needs to receive a defective gene from each of their parents. If both parents carry the gene, there is a 25% chance their child will have galactosemia.
This article delves into the causes underpinning galactosemia, the symptoms, and available treatment options.
Types and Causes of Galactosemia
A deficiency in one of the enzymes that break down galactose into glucose, which the body can use for energy, causes galactosemia.
The enzyme deficiency corresponds to the type of galactosemia:
- Type 1 galactosemia is the most common form of the disorder, also known as classic galactosemia. It is characterized by a GALT enzyme deficiency, which converts galactose-1-phosphate into glucose-1-phosphate.
- Duarte galactosemia is a milder disorder caused by a partial deficiency in the GALT enzyme. People with Duarte galactosemia have a reduced ability to break down galactose (roughly a 75% reduction) and can usually tolerate small amounts of galactose in their diet without experiencing symptoms. This form is more common than classic galactosemia.
- Type 2 galactosemia corresponds with a deficiency in the GALK enzyme, which converts galactose into galactose-1-phosphate.
- Type 3 galactosemia is the rarest form of the disorder, accounting for less than 5% of cases. Those with this type possess a deficiency in the GALE enzyme, which converts UDP-galactose into UDP-glucose.
- Type 4 galactosemia is caused by a GALM enzyme deficiency, which converts alpha-galactose to beta-galactose.[4]
When there is an impairment of the normal galactose metabolism pathway (Leloir pathway), as in galactosemia, the body activates alternative pathways to eliminate the excess galactose. However, these alternative pathways lead to the accumulation of toxic metabolites such as galactitol and D-gluconate, which build up in different tissues and can cause tissue damage.[5]
Specifically, aldose reductase, the first enzyme of the polyol pathway, converts excess galactose into galactitol. However, there is no way for the body to metabolize galactitol further, and it poorly diffuses through cell membranes. It accumulates in cells, disrupts the balance of fluids and electrolytes (hyperosmotic stress), and creates oxidative stress, which researchers believe is responsible for the cataracts observed in people with galactosemia.
Is Galactosemia the Same as Lactose Intolerance?
Lactose intolerance constitutes a deficiency in the enzyme lactase, which breaks lactose down. Galactosemia is a rare, genetic metabolic condition that demands a strict avoidance of galactose products, while lactose intolerance is usually a digestive or allergenic issue. People with lactose intolerance may still consume small amounts of lactose without experiencing symptoms[6]. The symptoms of lactose intolerance are far milder than those seen in galactosemia.
What are the Symptoms of Galactosemia?
In infants, symptoms appear shortly after birth after the baby ingests breast milk or formula containing galactose. They may display the following symptoms:
- Jaundice (yellowing of the skin and eyes)
- Poor ability to feed
- Poor weight gain and growth
- Vomiting
- Diarrhea
- Lethargy
- Irritability
Swift diagnosis and treatment are vital to prevent life-threatening complications in newborns.
As the infant develops, the following symptoms are commonly observed[7]:
- Enlarged liver
- Kidney problems
- Developmental delays
- Speech difficulties
- Learning disabilities
- Cataracts
If left untreated, galactosemia can lead to serious health complications, including liver damage, sepsis (blood infection), and brain damage[8].
How Does Galactosemia Affect Adults?
Adults with galactosemia may experience all the same symptoms listed above alongside any of the following[9]:
- Menstrual irregularities
- Infertility
- Early menopause
- Osteoporosis
- Cognitive impairment
- Speech difficulties
- Learning disabilities
- ADHD[10]
- Tremor
- Seizures
People with galactosemia require frequent health checkups to monitor their symptoms and tailor their treatment plans closely.
How is Galactosemia Diagnosed?
Galactosemia is typically diagnosed through a routine test performed during newborn screening, which measures the level of galactose-1-phosphate in the blood. If the level is high, further testing is necessary to confirm the diagnosis.
In addition to newborn screening, other tests that may diagnose galactosemia include:
- Red blood cell enzyme test: This screening test measures the activity of the GALT enzyme in red blood cells.
- Urinary ketones test: This test measures the level of ketones in the urine, which can indicate a problem with galactose metabolism.
- Blood culture for bacterial infection: Infants with galactosemia have elevated odds of acquiring E. coli sepsis. A blood culture can help in checking for bacterial infection.
- Genetic Testing: Galactosemia genetic testing can be done on CVS or amniotic fluid to assess the fetus's risk or confirm the diagnosis. After birth, genetic testing identifies the specific GALT gene mutation in babies with GALT enzyme deficiency.
Treatment for Galactosemia
The only treatment for galactosemia is a strict lactose-free diet. Infants must start this diet within 10 days of birth to avoid complications. Breastfeeding should be ceased and traded for lactose-free milk replacers.[11]
Using a galactose-free formula can speed up the reduction of high erythrocyte galactose-1-phosphate values in children with galactosemia.
Other options include:
- Casein hydrolysates formula options
- Soy-based formula options
The long-term safety of soy infant formulas is debatable due to plant isoflavones. A systematic review found no correlation between soy-based diets and puberty initiation in children.[12]
Both casein hydrolysates and soy-based formulas contain trace amounts of galactose.
With the introduction of solids, those with galactosemia must adopt a galactose-free diet for life. Galactose is a component of lactose and is in all dairy products. Lactose is also often a hidden ingredient in pre-processed foods and may be added to artificial sweeteners.[13]
Up to 20% of medications contain lactose. It is essential to check the ingredient lists of oral contraceptives, antacids, painkillers, antibiotics, and other medications.
The following ingredients are galactose-free despite being derived from dairy products and other foods:
- Lactate
- Lactic acid
- Lactalbumin
- Casein
Avoiding galactose and maintaining adequate calcium intake can promote weight gain, prevent liver and kidney issues, and even reverse cataracts, often resulting in sustained vision. However, it does not reverse all problems associated with galactosemia, such as ovarian insufficiency, speech problems, and early cognitive decline.
Supplementing with Calcium and Vitamin D: People with galactosemia are at an increased risk for bone problems, such as osteoporosis, due to their diet's lacking calcium and vitamin D. To prevent these issues, it is crucial to supplement with calcium and vitamin D, either through dietary intake or supplements.
HRT for Women: Women with galactosemia may experience early menopause due to the effects of the disorder on their ovaries. Hormone replacement therapy (HRT) may help manage symptoms and prevent complications.
Long-Term Management of Galactosemia
With early diagnosis and strict adherence to a lactose-free diet, the prognosis for people with galactosemia is good. However, if left untreated, the condition can result in serious health complications.
The life expectancy for people with galactosemia varies depending on the type and severity of the disorder. People with Duarte galactosemia generally have an average life expectancy, while those with type 1 or 2 galactosemia may have a slightly reduced life expectancy.
Individuals with galactosemia may require the expertise and care of multiple healthcare specialists throughout their lives. These specialists work together to provide comprehensive medical management and address the specific needs associated with galactosemia. Routine checkups for possible health problems can improve outcomes for patients.
Healthcare specialists that may be involved include[14]:
- Registered Dietitian for a nutritional assessment
- Metabolic Geneticist
- Endocrinologist for female hormone or bone density assessments
- Gastroenterologist
- Hematologist for metabolic evaluation and liver function testing
- Ophthalmologist to screen for cataracts
- Neurologist to assess cognitive function and neurodevelopment (in children)
- Psychotherapist
- Pediatrician/Primary Care Physician for regular health checkups
Communication and collaboration with the relevant specialists are essential to provide comprehensive care and optimize the management of galactosemia complications that may occur throughout the person's life.
Some children may require additional input, including a speech therapist or an occupational therapist, to help improve or work with developmental delays.
Latest Advancements in Galactosemia Treatment
While there is currently no cure for galactosemia, ongoing advancements in treatment options may improve the lives of people with the disorder.
One promising area of research is gene therapy, which concerns replacing or repairing the defective gene responsible for causing galactosemia. While this treatment is still in the early stages of development, it has shown promising results in animal studies[15].
Conclusion
Galactosemia is an infrequently seen genetic disorder that can provoke serious health complications if left untreated. A deficiency in one of the enzymes responsible for breaking down galactose causes it. While galactosemia is incurable, a strict lactose-free diet can help manage symptoms and prevent complications. With early diagnosis and proper treatment, people with galactosemia can live long and healthy lives.
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