What is Galactose-1-Phosphate Uridyltransferase Deficiency?
Galactosemia is a genetic disorder that makes it difficult for the body to process a type of sugar called galactose. This condition was first identified in 1917, and the cause was determined to be faulty galactose processing in the 1950s. If not diagnosed and treated quickly, newborns with galactosemia may become extremely sick just days after being born. Thankfully, in developed countries, newborn screening tests help detect this condition early on.
However, doctors need to be very wary of this condition, especially when treating sick newborns. Babies with galactosemia often struggle with feeding, may show an enlarged liver, sleep more than normal, have blood clotting issues, and kidney problems within a few days of being born. Sometimes, these symptoms appear before the results of newborn screening tests are available. Therefore, it is crucial that doctors recognize these signs and act promptly to treat the newborn.
What Causes Galactose-1-Phosphate Uridyltransferase Deficiency?
The GALT gene located on chromosome 9p13 creates a protein called galactose-1-phosphate uridylyltransferase. This protein helps convert a type of sugar, called galactose-1-phosphate, into another form called UDP-galactose. If the body doesn’t have enough of this protein, a condition called classic galactosemia can occur.
Similarly, the GALK1 gene on chromosome 17q24 produces a protein named galactokinase, which converts galactose into galactose-1-phosphate. The GALE gene on chromosome 1p36-p35 creates UDP-galactose 4-epimerase – vital for converting UDP-galactose to UDP-glucose, which can be used to create energy in our bodies.
If a baby inherits a faulty copy of these genes from both parents (who are carriers, but usually do not have symptoms themselves), there is a 25% chance it could experience galactosemia’s symptoms.
A type of galactosemia, called Duarte galactosemia, is caused by reduced activity of the galactose-1-phosphate uridylyltransferase enzyme (around 14% to 25%). People born with this form are usually asymptomatic, irrespective of what they eat. This means that people with Duarte galactosemia might not require treatment. However, there are some contradicting reports, and further studies are needed to fully understand the potential effects of reduced GALT activity on brain development over time. Newborn screening tests might not always detect Duarte galactosemia.
Risk Factors and Frequency for Galactose-1-Phosphate Uridyltransferase Deficiency
Galactosemia, a condition found in about 1 out of every 19,000 to 44,000 infants in Europe and the United States, is more common in certain ethnic groups. Specifically, it’s seen most frequently within the Irish Traveler community, where the incidence jumps to 1 in 480 infants. This condition is passed down through families in an “autosomal recessive” manner.
Signs and Symptoms of Galactose-1-Phosphate Uridyltransferase Deficiency
Galactosemia is a condition that manifests in infants, usually showing up in the first few days after birth. The first signs often include yellowing of the skin and eyes (jaundice), an enlarged liver (hepatomegaly), tiredness (lethargy), and serious difficulties with feeding as soon the baby starts consuming dietary galactose, which can be found in breast milk or most of the standard infant formulas. This condition may also lead to additional health issues.
- Poor weight gain
- Kidney failure
- Blood clotting disorder (coagulopathy)
- Low blood sugar (hypoglycemia)
- Seizures
- Swelling of the brain (cerebral edema)
- Cataracts
- Bleeding within the eye (vitreous hemorrhage)
- Low number of a type of white blood cell (neutropenia)
- Infections with E. coli bacteria (sepsis)
Upon diagnosing Galactosemia, it’s important to follow up long-term because there can be an impact on the child’s cognitive and motor skills development, difficulties with speech, low bone density, movement disorders (like ataxia or tremor), and premature ovarian failure.
Testing for Galactose-1-Phosphate Uridyltransferase Deficiency
In developed countries, the initial screening of newborns usually helps identify Galactosemia, a rare genetic disorder that affects the body’s ability to process galactose, a type of sugar. This screening checks for the activity levels of relevant enzymes, enabling diagnosis even before the baby has been fed foods containing galactose. Nevertheless, if a baby has had a blood transfusion before the screening, this may give false normal results as the donated blood may have normal enzyme activity.
Often, severe symptoms such as feeding difficulties, lethargy, enlargement of the liver, kidney failure, cataracts (clouding of the eyes), low blood sugar levels, and seizures may appear within the first few days after birth – even before the newborn screening results are finalized. For that reason, doctors need to be vigilant for such metabolic disorders like Galactosemia, particularly when the newborn displays suspicious symptoms.
If a baby is known to be at a high risk of Galactosemia during pregnancy, procedures like amniocentesis or chorionic villus sampling can be performed to confirm or rule out Galactosemia before the baby is born.
Postnatal newborn screening for this disorder is common in the US and Europe. However, it’s important to note that some communities with high instances of Galactosemia might not deliver at hospitals where such services are available. If Galactosemia is suspected in a baby, tests checking for GALT (an enzyme related to this condition) activity in red blood cells or GALT gene analysis should be conducted.
In the long term, monitoring levels of Calcium and Vitamin D is recommended each year. If necessary, supplements might be given in accordance with guidelines for the baby’s age group in the general population.
There’s some variation among treatment centers concerning biochemical monitoring. Common tests may include blood galactose, RBC Gal-1-P (a specific form of galactose found in red blood cells) , and/or urinary galactitol levels. However, it’s still not clear whether monitoring these levels is reflective of how well the prescribed diet is being followed or corresponds with clinical outcomes. Nonetheless, Gal-1-P levels are recommended to be checked at birth, at three and nine months, and yearly after that.
Developmental milestones, intellectual development, and speech and language progress should be assessed regularly at key stages like toddler, preschool, elementary, middle school, and high school ages. The use of a standardized tool is recommended to assess executive function, that is, the set of mental skills that include working memory, flexible thinking, and self-control.
Starting around eight to ten years of age, bone density should be checked using a bone density scan, and repeated every five years or earlier if low bone density is found. If cataracts are detected, a visit to an eye doctor is recommended.
More than 80% of girls with classic Galactosemia have primary ovarian insufficiency, which means their ovaries don’t work properly. It’s essential to discuss this with them before they hit puberty. A referral to a Pediatric Endocrinologist is appropriate to discuss when and how to test hormone levels and the potential requirement for hormone replacement therapy, which is typically administered until the usual age of menopause. In contrast, boys with Galactosemia usually have normal reproductive functions. Counseling about reproductive options should be offered to girls with primary ovarian insufficiency.
Treatment Options for Galactose-1-Phosphate Uridyltransferase Deficiency
The treatment for galactosemia, a rare genetic disorder, involves completely eliminating galactose, a type of sugar, from the patient’s diet. For babies, this means they cannot be breastfed or given standard baby formula. Instead, they need to switch to a special formula that does not contain galactose. This could be a soy-based formula, a casein hydrolysate formula, or an elemental formula. This diet change should happen immediately, even before final test results come in to confirm the condition.
Unfortunately, a person with this disorder will have to stick to a galactose-free diet for their whole life. These dietary restrictions might seem quite extreme, but keep in mind that there are several foods, including some fruits, vegetables, legumes, unfermented soy-based products, and mature cheeses, that have minimal galactose content and can be eaten. Currently, no medicine or therapy can allow a person with galactosemia to safely consume galactose.
In cases of a specific type of this disorder called Duarte variant galactosemia, it’s not clear whether it’s necessary to limit the intake of galactose. This decision is often left up to the patient’s doctor or parents, particularly during infancy and early childhood. However, it’s important to understand that the pros and cons of this diet restriction are still a subject of debate.
What else can Galactose-1-Phosphate Uridyltransferase Deficiency be?
When talking about certain medical conditions, it’s helpful to have a simple list. Here are some conditions that medical professionals consider:
- Biliary atresia
- Fructose 1 phosphate aldolase deficiency
- Fanconi Bickel syndrome
- Galactose kinase deficiency
- Hemochromatosis
- Hereditary fructose intolerance (HFI)
- Portosystemic vascular shunts
- Neonatal hemochromatosis
What to expect with Galactose-1-Phosphate Uridyltransferase Deficiency
If severe classic galactosemia, a serious medical condition, is left untreated, it can be life-threatening. Infants with galactosemia who are extremely sick, such as those with sepsis (a severe infection that spreads in the bloodstream), coagulopathy (a condition where the blood does not clot properly), or liver dysfunction (where the liver does not work as it should) may develop irreversible damages to their liver, brain, or eyes. However, it’s worth noting that cataracts (a clouding of the lens of the eye) are often completely reversible.
It is crucial to understand that most patients with severe galactosemia may not survive beyond the newborn period if they are not treated timely and properly.
Possible Complications When Diagnosed with Galactose-1-Phosphate Uridyltransferase Deficiency
Even when following a proper diet, most patients with this condition live with one or two long-term complications. Almost all are females with a condition called classic galactosemia, presenting with a type of ovarian insufficiency, which reduces the function of the ovaries.
In the case of seriously ill infants with galactosemia – including those suffering from blood poisoning, blood clotting disorders, liver dysfunction – they may suffer permanent damage to their liver, brain, or eye. However, one bright spot is that cataracts, if they occur, are usually completely reversible.
If not treated promptly after birth, most patients with severe cases of galactosemia won’t survive.
Key Complications:
- Living with one or two long-term complications despite proper diet
- Most females developed a reduced function of ovaries
- Seriously ill babies may have permanent liver, brain, or eye damage
- Eye damage can sometimes be reversed if it’s in the form of cataracts
- Likely death if severe galactosemia isn’t treated immediately after birth
Preventing Galactose-1-Phosphate Uridyltransferase Deficiency
In managing conditions that require a diet limited in galactose (a type of sugar), it’s crucial that both parents and children play an active role. As patients grow older, they generally handle milk, which contains galactose, better. Therefore, it’s important to have a discussion about the advantages and disadvantages of reducing milk intake.