Classic Galactosemia Screening -Infant

Summary of Recommendation and Evidence

Population	Recommendation	Grade (What's This?)
Screening of both Genders	The genetic screening for Classic Galactosemia is recommended.	B

OVERVIEW

Galactose is found in many foods and is produced when lactose is split by lactase into glucose and galactose. Three enzymes are involved in the metabolism of galactose into uridine diphosphate (UDP)-glucose and, ultimately, to carbon dioxide. Mutations of each of these genes can result in galactosemia:

Galactose-1-phosphate uridyl-transferase (GALT) deficiency results in Classic Galactosemia, where homozygotes have less than 5% enzyme activity. Duarte variant galactosemia, with between 10% and 25% activity, results from the compound heterozygote state with a GALT mutation and a Duarte allele.
Galactokinase 1 (GALK1) deficiency may cause cataracts and pseudotumor cerebri. These individuals have normal GALT enzyme activity.
UDP-galactose-4-epimerase (GALE) deficiency can cause a benign form, in which the deficiency is found only in red blood cells and no symptoms result, and a severe form, in which the deficiency affects most tissues resulting in symptoms similar to classic galactosemia. These individuals have normal GALT enzyme activity.

Symptoms of galactosemia are the result of inadequate energy production (due to lack of conversion to glucose) and accumulation of galactose and its metabolites (specifically galactose-1-phosphate). Accumulation of galactitol, the product of an accessory metabolic pathway, can result in cataracts and pseudotumor cerebri.

SCREENING

Finding

Deficiency of galactose-1-phosphate uridylyltransferase (GALT)

Tested By

Semiquantitative, fluormetric GALT enzyme assay; false positives may result from specimen exposure to excessive heat; transfusion prior to specimen collection can result in a false negative screen.

PREVALENCE

Classic galactosemia occurs in about 1 in 30,000 live births; Duarte variant occurs in about 1 in 16,000.

INHERITANCE

Classic galactosemia is inherited in an autosomal recessive manner. It affects both boys and girls equally.

PRENATAL TESTING

DNA testing possible by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected family member have been identified. GALT enzyme activity is also possible.

OTHER TESTING

Genetic testing is possible for at-risk family members if both disease causing mutations of an affected family member have been identified. Carrier testing by measuring GALT enzyme activity for at-risk family members is also possible.

CLINICAL CHARACTERISTICS

For classic galactosemia, symptoms develop shortly after starting to ingest milk or other lactose containing foods. With treatment, good health may be expected. Even with therapy, some patients with classic (G/G) galactosemia can have speech defects, poor intellectual function, neurologic deficits (predominantly extrapyramidal findings with ataxia), and ovarian failure with primary amenorrhea or early menopause. Without treatment, hepatic and neurologic injury and increased risk of sepsis may lead to death.

Initial signs/symptoms may include:

Poor feeding
Vomiting
Diarrhea
Jaundice
Bleeding diasthesis
Lethargy
Abdominal distention with hepatomegaly
Increased risk of sepsis with gram negative organisms

If not treated promptly, patients may experience:

Progressive liver failure
Cataract
Brain damage

EARLY SIGNS

Signs of classic galactosemia (GALT) can appear within a few days after birth.

Early signs of GALT include:

Poor weight gain and growth (known as failure to thrive)
Poor feeding and sucking
Vomiting
Diarrhea
Sleeping longer or more often
Tiredness
Irritability
Low blood sugar (hypoglycemia)

Many of these signs may occur when your baby eats foods that his or her body cannot break down.

CAUSES

When we eat food, enzymes help break it down. We need to break down the carbohydrates and sugars we eat so that they can be used for energy. Many foods, such as milk products and some fruits and vegetables, contain the sugar galactose. Galactose is broken down by several enzymes, including galactose-1-phosphate uridyl transferase (GALT enzyme).

If your baby has classic galactosemia (GALT), the GALT enzyme is either missing or not working correctly. When this enzyme does not work correctly, your baby’s body cannot break down galactose and undigested sugars build up in the blood. This build-up can damage important tissues and organs.

GALT is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for GALT, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with GALT is rare, when both parents are carriers, they can have more than one child with the condition.

TREATMENT

Dietary Treatment

Your baby may need to avoid foods with lactose and galactose (sugars found in milk) to prevent the toxic build-up of undigested sugars in his or her blood. Many children with classic galactosemia (GALT) need to avoid all milk products.

Your baby’s doctor can recommend foods and formulas that do not contain lactose or galactose. This diet will likely need to continue through adulthood.

Certain medications, candies, fruits, and vegetables also contain galactose. Your baby may need to avoid these as well. A dietician or nutritionist can help you plan a healthy diet for your child.

Supplements

Since many children must avoid milk-containing products, your baby may need to take calcium supplements. Your baby’s doctor may also prescribe Vitamin C and Vitamin K supplements.

EXPECTED OUTCOMES

With early and careful treatment, your child will most likely have a healthy life. Starting treatment shortly after birth can help prevent developmental delays and intellectual disabilities. This is why newborn screening for classic galactosemia (GALT) is so important.

Some children with mild forms of GALT may not need any special treatment.

Even if a child avoids all foods that contain galactose, a small buildup of undigested sugars may still occur because the human body makes a small amount of this on its own. Some children with classic galactosemia who receive treatment early still show delays in learning, development, speech/language, and motor skills.

Without treatment, babies with GALT are at risk of developing vision trouble, liver trouble, low blood sugar (called hypoglycemia), blood infections, developmental delays, and intellectual disabilities. Babies who do not receive treatment can die within their first weeks or months of life.