Galactosemia Confirmation Test, Blood

CPT CODE:

USEFUL FOR:

Diagnosis, carrier detection, and determination of genotype of GALT deficiency, the most common cause of galactosemia
Differentiating D/G mixed heterozygotes from classical galactosemia
Confirming results of newborn screening programs

SPECIMEN REQUIRED:

Draw blood in a lavender-top (EDTA) tube(s) from a fasting (4 hour) patient, and send 5 mL of EDTA whole blood refrigerated. Specimen cannot be frozen.  Note:    Patient's age is required on request form for processing.

TRANSPORT TEMPERATURE:

Refrig\Ambient OK\Frozen NO

CLINICAL INFORMATION:

Galactosemia is an autosomal recessive inborn error of galactose metabolism. Deficiencies of 3 clinically important enzymes that catalyze the conversion of galactose to glucose and result in galactosemia have been described: deficiency of galactokinase (#8628 "Galactokinase, Blood"), UDP galactose-4-epimerase (GALE), and galactose-1-phosphate uridyltransferase (GALT).
The GALT deficiency, referred to as classical galactosemia or G genotype, is the most commonly occurring of the 3 disorders. Typically, individuals with classic galactosemia are diagnosed vianewborn screening and a lactose-restricted diet is initiated during the neonatal period (lactose is metabolized to galactose and glucose). In the unfortunate circumstance where diagnosis and dietary treatment is delayed, infants usually present with gram-negative sepsis, inanition (weakness and weight loss due to severe lack of food), failure to thrive, vomiting, life-threatening liver disease, cataracts, and ultimately, mental retardation if galactose ingestion continues. Treatment with lactose-restricted diet can typically reverse the acute symptoms. Mild growth retardation, cognitive impairment,and intellectual deficit have been variably described as complications of treated galactosemia in some patients.  Ovarian dysfunction is an almost unavoidable consequence of classic galactosemia, even with adherence to a strict diet. Osteoporosis secondary to decreased calcium intake can also occur.
Several disease-causing mutations are commonly encountered in classical galactosemia. The most frequently observed is the Q188R classical mutation, which has been reported to account for 54%-70% of classical galactosemia alleles. The S135L mutation is the most frequently observed mutation in African-Americans and accounts for approximately 50% of the mutant alleles in this population. The K285N mutation is common in those of eastern European descent and accounts for 8% of the alleles in thegeneral European population. The L195P mutation is observed in 2.6% of classical galactosemia cases.
The Duarte N314D mutation is found in 5% of the general UnitedStates population and, when paired with a classical galactosemia mutation, results in D/G mixed heterozygote. D/G mixed heterozygosity typically results in a benign phenotype, but may be treated with a low lactose-containing diet during infancy. D/G mixed heterozygotes may mimic classical galactosemia in the biochemical assays used in newborn screening (reduc

CLINICAL INTERPRETATION:

This test detects 4 of the most frequently encountered classical galactosemia alleles (Q188R, S135L, K285N, and L195P),as well as the N314D Duarte and L218L Los Angeles variants.
The laboratory provides an interpretation of the results, including GALT enzyme activity, genotype, and biochemical phenotype, if necessary. This interpretation provides an overview of the results and their significance, a correlation to available clinical information, elements of differential diagnosis, and recommendations for additional testing.
Any specimen where enzyme activity is <18.5 U/g hemoglobin will be analyzed for the presence of the 4 mutations associated with classic galactosemia, as well as the 2 variants(Duarte and Los Angeles). See "Galactosemia Testing Algorithm" in Special Instructions for testing algorithm.
Galactosemia occurs in patients whose enzymes levels are extremely low.
For dietary compliance, refer to #80337 "Galactose-1-Phosphate, (Gal-1-P), Erythrocytes."
See "Galactosemia Testing Algorithm" in Special Instructions for additional information.

REFERENCE VALUES:

> or = 18.5 U/g of hemoglobin