What is Galactokinase Deficiency (Galactosemia Type II)?
Galactokinase deficiency, also known as type II galactosemia, is a genetic disorder that affects how the body processes a sugar called galactose. This type of galactosemia is less common, and not as noticeable as other types because it mainly causes the formation of cataracts (a clouding in the lens of the eye) without causing other noticeable symptoms such as digestive or systemic problems.
What Causes Galactokinase Deficiency (Galactosemia Type II)?
Galactokinase deficiency is a condition that happens due to a change, or mutation, in a specific gene known as the GALK1 gene. This gene is responsible for creating the galactokinase enzyme. Genes are inherited from our parents and this disorder follows what’s called an “autosomal recessive” pattern. This means the condition only occurs when a child gets two copies of the faulty gene – one from each parent.
Scientists have spotted more than 30 different types of changes in this gene in people who have galactokinase deficiency.
Risk Factors and Frequency for Galactokinase Deficiency (Galactosemia Type II)
Galactokinase deficiency is not a very common condition, with its occurrence ranging from 1 in 50,000 to as rare as 1 in 2,200,000. It is more prevalent in the Romani population, where 1 in 47 people carry the disease. In the United States, about 1 in 100,000 newborns are affected by this condition.
Signs and Symptoms of Galactokinase Deficiency (Galactosemia Type II)
Galactokinase deficiency is a rare hereditary metabolism disorder that tends to not show noticeable symptoms in infants. When there are symptoms, they often include high bilirubin levels and cataracts. If not identified early, these cataracts can impact the baby’s ability to display a social smile or visually track objects.
Another symptom that can appear is pseudotumor cerebri. This is due to a rise in the cerebrospinal fluid’s osmotic pressure, triggered by an increase in galactitol concentration. If the symptoms are left unchecked for a long time, the child might be at risk of issues like dyspraxia, mental retardation, motor development delays, and lower-than-normal gonad function. There’s also an increased risk for adults who carry the galactokinase deficiency gene to develop cataracts at an early age.
Other symptoms that have been reported in studies include small head size, failure to grow appropriately for their age, seizures, hearing loss in both ears, low blood sugar, high cholesterol levels, enlarged liver, and ovarian failure. It’s still not clear if these symptoms are directly linked to the deficiency of the galactokinase enzyme.
There are also reports of patients with galactokinase deficiency having severe high blood sugar levels that cannot be detected using a standard bedside glucose test. This could occur due to the build-up of galactose in the body.
Testing for Galactokinase Deficiency (Galactosemia Type II)
If a newborn has cataracts or abnormal results in their newborn screening tests, they could potentially have a rare condition called galactokinase deficiency. This is a disease that affects how the body processes a sugar called galactose. Doctors usually can detect it by looking for signs of too much galactose in the body.
There’s a special test called the Beutler fluorescent spot screening test that a doctor might want to run if they suspect this condition. Other tests might include checking how well an enzyme called GALT is working. If its level is less than 24.5 nmol/h/mg of hemoglobin, it could mean the baby either has classic galactosemia or a related condition called Duarte-variant galactosemia. If that’s the case, the doctor could request a gene analysis.
If the baby’s GALT levels are more than 24.5 nmol/h/mg of hemoglobin, but there’s still too much galactose in their body, the doctor might want to run a test on their red blood cells or do a galactokinase enzyme assay. Various diagnostic programs use different methods to determine GALT activity.
Some screening programs measure total galactose (including Galactose-1-phosphate or Gal-1-P) either on its own or alongside GALT testing. A negative result for galactosemia, therefore, must take into account the type of test conducted. If required to monitor the baby’s diet, doctors typically measure GAL1P/Gal-1-Phos levels in the baby’s red blood cells.
In comprehension of patients with galactokinase deficiency, doctors can study the level of galactose in early morning urine samples to check if patients’ diets are being followed correctly. Doctors may also find that the levels of galactose and a substance called galactitol are high in the urine and blood of people with this condition. But much of the time, with a galactose-restricted diet, the amount of this sugar in the blood can be reduced or even brought back to normal.
If doctors suspect a condition called pseudotumor cerebri (a rare condition where the pressure inside the skull increases for no obvious reason) in a baby with galactokinase deficiency, they may perform an in-depth examination of the baby’s eyes and brain scans. Then, they might carry out a lumbar puncture – a test where a needle is used to take a sample of fluid from the spine – to measure the pressure of the baby’s cerebrospinal fluid (the fluid around the brain and spinal cord).
For genetic testing for galactokinase deficiency, doctors usually look at the entire sequence of the GALK gene and check for any deletions or duplications in the gene rather than looking for specific mutations.
If a newborn is diagnosed with any form of galactosemia (including galactokinase deficiency), genetic counseling ought to be provided to the families involved. This is because the condition is passed down in an autosomal recessive fashion, meaning both parents must carry the faulty gene for the baby to have the disease. The chance of the disease occurring in a future pregnancy is at least 25 percent. Options for carrier screening, prenatal testing through amniocentesis or chorionic villus sampling, or preimplantation genetic testing can be discussed with families who are at risk of having a child with galactosemia.
Treatment Options for Galactokinase Deficiency (Galactosemia Type II)
If a baby is born with a condition that causes high levels of galactose (a type of sugar) in their body, it’s very important to start them on a special diet with reduced galactose as quickly as possible. This could also involve adding calcium supplements to their diet. This approach can significantly lower the levels of the harmful byproducts that galactose can turn into in the body.
While it’s essential to limit major sources of galactose in the diet, small amounts found in foods like legumes, green vegetables, and dairy products are not typically a concern. It’s generally assumed that small amounts of galactose are processed and removed from the body before they can turn into harmful substances.
If this special diet is started within a few weeks of the baby’s birth, it can even help to clear up cloudiness in their eyes, known as a cataract. In cases where the cataract has become too dense or mature, it may need to be surgically removed.
Switching infants to a soy-based formula is often a part of this dietary intervention. While babies following this diet usually develop as expected, recent research has found an increased risk of developmental issues.
Long-term care for these children typically involves frequent testing of the levels of galactose and the substances it turns into in the body. This includes careful monitoring of the levels of a substance called galactitol in red blood cells. Regular eye exams are necessary to catch and treat any early signs of developing cataracts.
In cases where the child has developmental delays or learning difficulties, they may also need regular developmental testing. Regular blood sugar checks are necessary because there is a risk of low blood sugar associated with this condition.
What else can Galactokinase Deficiency (Galactosemia Type II) be?
“Classic galactosemia” is a genetic disorder that’s usually spotted in newborns. It leads to serious problems like feeding issues, failure to gain weight properly, liver damage, severe bacterial infections, and excessive bleeding. However, if a special diet is started within the first ten days of life, these problems can be avoided.
“Duarte galactosemia” is a similar genetic disorder with somewhat milder symptoms. It’s often missed in newborn screenings because it doesn’t markedly raise galactose (a type of sugar) levels in the blood like classic galactosemia does. Still, severe symptoms can be prevented if treatment begins within the first ten days of life.
Another type of galactosemia is “Epimerase deficiency galactosemia”. This should be considered if a baby isn’t gaining weight well, has liver disease, and shows high galactose levels in red blood cells, but normal enzyme activity. The condition can be confirmed by finding reduced GALE enzyme activity.
What to expect with Galactokinase Deficiency (Galactosemia Type II)
The outlook is very good if people continue to avoid eating galactose, a type of sugar. Proper treatment can prevent the development of cataracts, which are clouding of the eye’s lens, or at least partially reverse them if treatment starts before the cataract fully forms.
Possible Complications When Diagnosed with Galactokinase Deficiency (Galactosemia Type II)
The two main problems typically seen in patients with galactokinase deficiency are the development of cataracts and pseudotumor cerebri. Even when these patients follow a strict diet, some still experience delays in mental and physical growth, trouble with physical coordination (dyspraxia), and a condition known as hypogonadotropic hypogonadism, which affects the production of hormones that control sexual growth and development.
Common Complications:
- Cataracts
- Pseudotumor cerebri
- Delay in mental and physical development
- Dyspraxia (coordination problems)
- Hypogonadotropic hypogonadism (sexual development problems)