Galactosemia

Galactosemia

Article
Diseases & Conditions
Congenital & Genetic Disorders
Contributed byKrish Tangella MD, MBAMar 31, 2018

What are the other Names for this Condition? (Also known as/Synonyms)

  • Epimerase Deficiency Galactosemia
  • Galactose-1-Phosphate Uridyl-Transferase Deficiency Disease
  • UTP Hexose-1-Phosphate Uridylyltransferase Deficiency

What is Galactosemia? (Definition/Background Information)

  • Galactosemia is a genetic disorder in which the body is unable to convert a sugar, called galactose, into energy. It is caused by mutations in the GALE, GALK1, and GALT genes
  • Galactose is a simple sugar, just like glucose. Glucose is the most common type of sugar that the body converts into energy. Galactose is a part of lactose, which is present in milk and milk-products, including baby formulas
  • There are 3 different types of Galactosemia, caused by mutations in different enzymes that are responsible for metabolism of galactose. They are classified as:
    • Galactosemia Type I: Classic Galactosemia Type I is the most common type, with the most severe signs and symptoms. In this type, the mutation occurs in GALT gene
    • Galactosemia Type II: Caused by mutations in the GALK1 gene, resulting in galactokinase deficiency
    • Galactosemia Type III: Caused by mutations in the GALE gene, resulting in galactose epimerase deficiency
  • Like the enzyme produced from GALT gene, the enzymes made from the GALK1 and GALE genes play a role in processing galactose. A shortage of any of these critical enzymes, allows galactose and related compounds to build up to toxic levels in the body. The accumulation of these substances, damages tissues and organs, leading to the characteristic features of Galactosemia

Who gets Galactosemia? (Age and Sex Distribution)

  • Galactosemia is a congenital genetic disorder, which may cause signs and symptoms, right from birth
  • Classic Galactosemia Type I, which is the most common form, occurs with a frequency of 1 in 30,000 to 60,000 births.
  • Galactosemia Types II and III occur with a much lesser frequency. It is estimated that Galactosemia Type II occurs in less than 1 in 100,000 live births. The incidence of Type III Galactosemia is not known, but their occurrence is very rare
  • Both males and females are affected by this disorder

What are the Risk Factors for Galactosemia? (Predisposing Factors)

Galactosemia is a genetic disorder inherited in an autosomal recessive manner. Individuals with a family history of the condition are at a great risk of inheriting Galactosemia.

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Galactosemia? (Etiology)

  • Galactosemia is caused by mutations in the GALE, GALK1, and GALT genes. These genes are responsible for converting dietary galactose into energy, which the body can use
  • All Galactosemia types are genetic disorders inherited in an autosomal recessive pattern. This means that both copies of the genes (one obtained from each of the parents) have to be mutated to cause the disorder. If one gene is mutated and other is normal, then the individual is considered to a carrier of the disorder; such carrier individuals, do not suffer from signs and symptoms of Galactosemia
  • The body's lack of ability to metabolize galactose, results in accumulation of toxic substances in different parts of the body. These cause the signs and symptoms of Galactosemia, which also depend on the specific type (Type I, II, or III) of the disorder. Higher the levels of toxic accumulation, greater are the severity of signs and symptoms
  • Classic Galactosemia Type I is the most common type, with the most severe signs and symptoms. In this type, mutation occurs in the GALT gene; there are two variants of GALT gene mutations:
    • In a majority of the cases, the mutations in GALT gene cause a total loss of enzyme activity, leading to a complete lack of galactose metabolism in the body. This results in life-threatening signs and symptoms
    • In a minority of the cases, GALT gene mutation (called the Duarte variant) decreases, but does not completely eliminate the activity of the enzyme. Individuals with the Duarte variant, usually have much milder signs and symptoms of Galactosemia
  • Galactosemia Type II and Type III are caused by gene mutations, resulting in galactokinase deficiency and galactose epimerase deficiency, respectively

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Galactosemia?

The signs and symptoms of Galactosemia depend on the type of the disorder. Type I has more severe signs and symptoms, compared to Type II and Type III Galactosemia.

  • In Type I Classic Galactosemia, the infants fed with galactose, accumulate toxic levels of compounds quickly, resulting in life threatening complication within weeks. Such infants should not be given any form of galactose, right from birth
  • Signs and symptoms of  Type I Classic Galactosemia  include:
    • Difficulties in feeding
    • Lack of energy (lethargy)
    • Failure to gain weight and grow as expected (failure to thrive)
    • Jaundice due to liver failure, resulting in yellowing of the skin and white of the eyes
    • Bone marrow failure resulting in severe bacterial infections (sepsis)
    • Bleeding
    • Multi-organ failure
  • In less severe cases, such as in Type II and Type III Galactosemia, the presentations include:
    • Cataracts
    • Short stature
    • Infertility
    • Mental disabilities

How is Galactosemia Diagnosed?

A diagnosis of Galactosemia would involve:

  • Physical exam with evaluation of medical history; neonates are usually screened for this disorder, if the physician suspects the same
  • Urine and blood exam - blood sugar and plasma, amino acid analysis
  • Blood culture test, to detect any infection (due to bacteria)
  • Genetic tests and analysis for mutations, in order to determine the exact type of the condition
  • Prenatal exams, in order to measure certain enzymes

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Galactosemia?

Complications due to Galactosemia could include:

  • Liver enlargement - could progressively lead to liver cirrhosis and liver failure
  • Visual impairment from cataract
  • Mental disabilities, delayed speech development
  • Severe bacterial infection
  • Low blood sugar
  • Uncontrollable and involuntary bouts of muscle movement, tremors, lack of coordination
  • Ovarian failure, resulting in infertility
  • Reduced density of bones causing frequent fractures, even on ‘minimal-impact traumas’

How is Galactosemia Treated?

Management of Galactosemia is undertaken on a case-by-case basis, depending on the disorder type, and severity of signs and symptoms. However, Galactosemia is a genetic condition that cannot be cured.

The treatment measures considered are dependent upon the age of the individual, the disease stage, and acuity of the symptoms. These include:

  • Avoidance of galactose and lactose (in any form) completely from the diet; the mother’s milk is substituted by a soy-based formulaic preparation
  • Calcium supplementation (along with vitamin D), which is required for the development of bones and muscles

How can Galactosemia be Prevented?

  • Currently, there are no specific methods or guidelines to prevent Galactosemia genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
  • Avoiding any food item that contains galactose (in any form) is very important, in controlling the severity of the condition
  • Regular medical screening at periodic intervals with tests and physical examinations are mandatory for those affected by Galactosemia

What is the Prognosis of Galactosemia? (Outcomes/Resolutions)

  • Galactosemia is a genetic disorder that manifests at birth and having potential life-threatening consequences. Early detection and strict avoidance of galactose are the two key factors, to having a normal life
  • Physical impairment and mental growth delays often accompanies this disorder; however, the severity of Galactosemia can be controlled, with timely and appropriate medical care
  • A delay in diagnosis of the disorder, leading to a delay in treatment, could be fatal during the infancy stage

Additional and Relevant Useful Information for Galactosemia:

There are voluntary organizations and support groups that provide help and understanding to the families and parents of the Galactosemia disorder affected.

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Krish Tangella MD, MBA picture
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Krish Tangella MD, MBA

Pathology, Medical Editorial Board, DoveMed Team

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