Lab Profiles UPDATED

Condition: Galactosemia

"Galactosemia is caused when a baby cannot digest sugar found in milk. The condition leads to cataracts, liver damage, mental retardation and usually death. Substituting a special formula for milk starting in the first weeks of life helps to avoid these problems" - Vermont Newborn Screening

Technical information from the Mountain States Genetic Network:

Galactosemia is an elevation of blood galactose levels. It may be due to a deficiency of any of the three enzymes of the galactose catabolic pathway: galactose-1-phosphate uridyltransferase (Gal-1-PUT), galactokinase, or UDP-galactose-4-epimerase. Clinically, deficiency of galactose-1-phosphate uridyltransferase (Gal-1-PUT) has become synonymous with classic galactosemia. This autosomal recessive disorder occurs with an incidence of approximately 1:40-60,000 in the general population. The symptoms can be severe in infancy and may lead to death or severe neurologic damage if not recognized and treated.

Galactose is a monosaccharide present in many polysaccharides. Clinically, the most important source is the disaccharide lactose. Lactose is the predominant carbohydrate in human and most other animal milk, including cows milk. Many commercially available infant formulas contain lactose. However, other formulas, such as some soy-based formulas, do not contain lactose. This is critical information to assess in patients as ingestion of galactose is prerequisite to the development of clinical symptoms.

Clinical Features
Galactose-1-phosphate uridyltransferase deficiency (Gal-1-PUT)
Galactosemia, due to a complete lack of Gal-1-PUT activity, presents in the first weeks of life. The most prominent clinical features are liver dysfunction manifest as jaundice and hypoglycemia; neurologic findings of irritability and seizures; and gastrointestinal findings of poor feeding, vomiting, and diarrhea. Other findings include cataracts and renal Fanconis syndrome. Escherichia coli sepsis has been described in many patients with galactosemia. If the diagnosis of galactosemia is not made in the neonatal period, failure to thrive, chronic vomiting, hepatic cirrhosis, and mental retardation may develop in infants who survive. The diagnosis can be suspected clinically by the presence of the above symptoms, but some affected infants may be asymptomatic at the time of screening. Positive non-glucose urine reducing substances increases suspicion of the condition, but not all affected newborns will have a positive urine test.

There are several clinical variants due to genetic mutations in Gal-1-PUT that alter, but do not eliminate, enzyme activity. The most common of these are the Duarte and Los Angeles variants. Patients with these variants are usually clinically asymptomatic; however the reduced enzyme activity will be detected by newborn screening. Further testing is required.

Galactokinase deficiency
This is a rare defect manifest only by the development of cataracts, usually in the neonatal period, but occasionally delayed until adulthood. The toxic symptoms of Gal-1-PUT deficiency are not present, however the urine may be positive for reducing substances. Consideration of galactokinase deficiency should be given in any patient with an abnormal total galactose result and a normal Gal-1-PUT on the newborn screen.

UDP-galactose-4-epimerase deficiency
This is a very rare cause of galactosemia that may be either symptomatic or asymptomatic. Consideration should be given in any patient with an abnormal total galactose result and a normal Gal-1-PUT on the newborn screen.

Laboratory Tests
Two screening tests are presently used to detect galactosemia. All states in our region use the Gal-1-PUT screen; some states also screen for total galactose.
The Gal-1-PUT test depends upon fluorescence produced by the normal enzyme cascade in red blood cells. The test is abnormal when the enzyme activity is reduced and little or no fluorescence is observed. Patients with classic galactosemia have no enzyme activity; patients with a variant form will have reduced but not absent activity and fluorescence. Gal-1-PUT is sensitive to heat, so a false positive may result if the sample has been heat-damaged. Because the test assays enzyme activity in red blood cells, false negatives can result from a blood transfusion (the newborn screening specimen should always be obtained before an infant receives a blood transfusion).

Total galactose levels are determined using either fluorometric or colorimetric metabolite assays to detect accumulation of blood galactose. These test methods are dependent upon lactose consumption. If total blood galactose is elevated and the Gal-1-PUT test is normal, galactokinase or UDP-galactose-4-epimerase deficiencies, or a variant galactosemia, may be present.

The acute symptoms of the galactosemia syndromes are effectively treated by dietary exclusion of galactose; exclusion of milk and milk products alone does not constitute a galactose-restricted diet, as galactose is found in other foods as well. This galactose-restricted diet must be followed for life and requires close supervision and monitoring. Medical care of the patient also involves management of those symptoms not prevented by diet. Treatment for galactosemia is at present controversial, consultation with a metabolic physician is indicated. For assistance with management of galactosemia, refer to the directory for a metabolic consultant in your state.

Screening Practice Considerations
The Gal-1-PUT test should demonstrate no enzyme activity in all severe (classic) galactosemic infants with the exception of infants that have received a blood transfusion; in this situation infants with galactosemia may have a GAL-1-PUT test which is normal or is suggestive of a galactosemia variant, rather than classic galactosemia. Always obtain a newborn screening specimen before a transfusion. In patients who have received a transfusion prior to the collection of the newborn screening specimen, a newborn screening specimen should be obtained 90-120 days following the last transfusion and, if galactosemia is a clinical consideration, dietary restriction of galactose maintained until an accurate test has been obtained.
Prompt confirmatory testing is required even if there is evidence to suggest that one of the situations associated with false positive screens is present (these include early specimen collection, prematurity, heat-damaged specimen, hyperalimentation, or antibiotic therapy). The presence of any of these does not exclude the possibility of disease.

Elevation of blood galactose levels depends on lactose ingestion, so blood galactose should be normal in infants receiving non-lactose containing formulas.

The Gal-1-PUT test will be unaffected by the formula given to an infant. If galactosemia is a clinical consideration, especially in an infant with non-glucose urine reducing substances and clinical symptoms of galactosemia, begin a galactose-free formula immediately -- the Gal-1-PUT test will be unaffected by this potentially life-saving measure. If galactosemia is suspected, immediate consultation with a metabolic physician is advised.

The purpose of newborn screening is to identify infants at risk and in need of more definitive testing.
As with any laboratory test, both false negative and false positive results are possible.
Screening test results are insufficient information on which to base diagnoses or treatment.