What Is Galactosemia?

Galactosemia is a condition where the body does not convert one type of sugar molecule (galactose) into another (glucose). Both sugars are monosaccharides, making them the simplest building blocks for carbohydrates. Galactose and glucose are chemically similar but differ in the arrangement of their atoms. They both act as crucial sources of energy for human cells and hence, negative consequences arise when the metabolism of these sugars is disrupted.

Read the article to understand this condition in detail.

Overview

Galactosemia is a marked impairment of the body’s natural ability to process the sugar galactose into glucose. It is a genetic disorder that affects your metabolism. It has an autosomal recessive pattern of inheritance, meaning at least one parent needs to be affected by the disorder themselves, or both parents must be carriers of the gene mutation to pass galactosemia on to their offspring.. One of the most common mutations responsible for causing galactosemia occurs in the gene that encodes for the enzyme galactose-1-phosphate-uridylyl-transferase (GALT). In affected individuals, the enzyme GALT is deficient or completely absent. Hence, the body is not able to convert galactose into glucose, causing the accumulation of galactose and its unwanted metabolites in the blood. This may, in turn, lead to intellectual disabilities, liver failure and death in a newborn baby. As galactose is a major part of lactose, dairy products and breast milk are often avoided by patients suffering from galactosemia. 

Types of galactosemia

There are three different types of galactosemia:^1,2

Type I: Classic galactosemia

The most severe variant of galactosemia is known as the classic variant (type I). Affected patients are born without, or with very little, GALT enzymes. Life-threatening problems develop soon after birth in newborns with classic galactosemia if a galactose-free diet is not promptly followed. For a child to inherit classic galactosemia, both of its parents must pass on a defective copy of the GALT gene (carriers of the disease). This type of galactosemia is screened for during the newborn screening process. 

Duarte galactosemia similarly affects the GALT enzyme, but instead of a complete absence of the enzyme, patients affected by this variant have a mild enzyme deficiency. This galactosemia variant is much less severe, often not requiring any interventions for an individual to live a healthy life.

Type II: Galactokinase deficiency galactosemia

Type II Galactosemia prevents an affected individual from completely metabolising galactose due to a deficiency in the enzyme galactokinase. This type of galactosemia is caused by a mutation in the GALK1 (galactokinase) gene, an enzyme that catalyses steps in the metabolic pathway that converts galactose into glucose. Type II galactosemia has a relatively mild progression. Yet, it can be difficult to diagnose as typical newborn screening tests often fail to detect this galactosemia variant. 

Type III: Epimerase-deficiency galactosemia

Type III galactosemia is brought about by inheriting mutations in the GALE  (UDP-galactose-4′-epimerase) gene, which results in a partial loss of GALE enzyme activity that is required for galactose processing. GALE deficiency can be classified as generalised, intermediate, or peripheral. The severity of generalised GALE deficiency is comparable to that of classic galactosemia. Many newborn screening tests do not check for GALE deficiency galactosemia, preventing an early diagnosis from being made.

Signs and symptoms of galactosemia

Galactosemia may manifest itself as various clinical signs in infants and in the elderly:¹

Infant: 

• Issues with feeding
• Failure to flourish
• Liver problems
• Bleeding
• E.coli infection
• Sepsis

Elderly person:

• Untreated developmental delay
• Speech issues
• Motor function abnormalities, including extrapyramidal signs and ataxia
• Cataracts
• Liver disease or cirrhosis
• Early menopause

Diagnosis of galactosemia

Though newborn screening for conventional galactosemia has been established, galactokinase deficiency and UDP-galactose-4′-epimerase (GALE) insufficiency are not always detected. Newborn screenings for classic galactosemia consist of observing diminished GALT activity in dried blood spots (DBS) and measuring an increased level of galactose sugars in the blood. Tests relying solely on levels of galactose sugars in the blood may overlook cases of GALT deficiency in individuals on a galactose-limited diet. Confirmation of a galactosemia diagnosis is done through genetic testing, which identifies the specific mutations on either the GALT, GALE or GALK1 gene.²

Management and treatment of galactosemia

Infants and children with galactosemia should follow a lactose-restricted (dairy-free) diet, which includes alternative foods, such as soy products and lactose-free replacements. A strict diet should be implemented as soon as a diagnosis is established to improve the prognosis of the patient.

Affected individuals can produce galactolipids and other necessary galactose-containing substances without the use of food. Therefore, if a strict diet is followed, optimal physical growth and development are feasible.

In infants suffering from E. coli infections, antibiotic treatment is employed to control infection. Children may require care and supportive measures if the need to follow a strict diet is having an emotional effect on them. Individuals who have relatives affected by the condition or are affected themselves should seek genetic counselling to fully comprehend the risks of passing galactosemia to their children. Children who have acquired dysarthria or childhood apraxia of speech due to galactosemia may benefit from speech therapy. Individual education plans or professional assistance with learning skills may be required for some school-age children following an evaluation of their psychological development. In situations of delayed puberty and later in adolescence, the lack of regular menstrual cycles, hormone replacement therapies may be utilised.

Risk factors

Being born to parents who are both carriers of a galactosemia-causing mutation or to individuals who are affected by galactosemia is the main risk factor for developing the condition. 

Complications

Untreated newborns with classic galactosemia may experience life-threatening consequences, such as feeding issues, failure to thrive, liver damage, haemorrhage, and E. coli infection. Neonatal complications, like liver failure, sepsis, and neonatal death, can be avoided if a lactose-restricted diet is given during the first ten days of life. However, even with early and adequate treatment, children with classic galactosemia continue to have an increased risk of developmental delays, speech issues (also known as childhood apraxia of speech and dysarthria), and abnormalities in motor function. Premature ovarian insufficiency (POI) or hypogonadotropic hypogonadism are conditions commonly seen in females with classic galactosemia. 

Long-term complications associated with galactosemia are cataracts, learning disabilities, speech disorders, neurological impairments and early menopause.³

FAQs

How can I prevent galactosemia?

Although galactosemia cannot be prevented, complications can be avoided by removing galactose from your diet. Galactose must be eliminated from your diet to successfully manage it. Galactose is a part of lactose; hence, avoiding dairy products is usually required. Infants can be given an elemental or soy-based formula as a replacement for breast milk and dairy products.

How common is galactosemia?

Type I galactosemia (classic) is the most prevalent variant, occurring in 1 in 30,000 to 60,000 infants. In contrast, type II galactosemia is observed in less than 1 in every 100,000 infants, while type III is considered extremely rare.

When should I see a doctor?

A newborn with galactosemia first seems healthy, but within a few days or weeks, will begin to lose their appetite and begin to vomit. At this point, you should take your child to be evaluated by a doctor. If you miss the early signs of galactosemia, the following can serve as additional indicators that your baby needs to be taken to a doctor:²

• Jaundice, which is the yellowing of the skin, mucous membranes, and whites of the eyes
• Liver enlargement 
• The presence of amino acids and proteins in their urine 
• Failure to grow
• Fluid buildup in the abdominal cavity (ascites) 
• Diarrhoea 
• Irritability 
• Tiredness
• Signs of a bacterial infection 

If lactose is not eliminated from the diet immediately, significant weight loss, marked weakness, and body tissue atrophy can eventually take place.

Summary

Galactosemia is a condition characterised by the inability to effectively metabolise a sugar known as galactose. It is a genetic condition that causes the absence or a deficiency in the enzymes that catalyse the metabolic pathway used to convert galactose into glucose. Galactosemia can vary from mild to severe, depending on the mutation that is inherited. In most cases, the elimination of galactose from an affected patient’s diet can help manage the condition, improving their prognosis. If this is not achieved, the likelihood of complications rises, potentially causing individuals with galactosemia to suffer from developmental disabilities, liver damage and hormonal disruptions. Although current management consists of lifestyle changes and the treatment of secondary disorders, recent developments in the understanding of the molecular and cellular components of galactosemia should pave the way for the creation of brand-new treatment approaches.⁴