Galactosemia Gene Analysis (6-Mutation Panel)
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Classical galactosemia is an autosomal recessive disorder of galactose metabolism caused by mutations in the galactose-1-phosphate uridyltransferase (GALT) gene. The complete or near complete deficiency of the GALT enzyme is life threatening. If left untreated, complications include liver failure, sepsis, mental retardation, and death. Galactosemia is treated by a galactose-free diet, which allows for rapid recovery from the acute symptoms and a generally good prognosis. Despite adequate treatment from an early age, children with galactosemia remain at increased risk for developmental delays, speech problems, and abnormalities of motor function. Females with galactosemia are at increased risk for premature ovarian failure. The prevalence of classic galactosemia is approximately 1 in 30,000.
Duarte variant galactosemia (compound heterozygosity for the Duarte mutation, N314D, and a classic mutation) is generally associated with higher levels of enzyme activity (5%-20%) than classic galactosemia (<5%); however, this may be indistinguishable by newborn screening assays. Typically, individuals with Duarte variant galactosemia have a milder phenotype but are also often treated with a low galactose diet during infancy. The LA variant which consists of N314D and a second change, L218L, is associated with higher levels of GALT enzyme activity than the Duarte variant allele.
Newborn screening, which identifies potentially affected individuals by measuring total galactose (galactose and galactose-1-phosphate) and/or determining the activity of the GALT enzyme, varies from state to state. The diagnosis of galactosemia is established by follow-up quantitative measurement of GALT enzyme activity. If enzyme levels are indicative of carrier or affected status, molecular testing for common GALT mutations may be performed. If 1 or both disease-causing mutations are not detected by targeted mutation analysis and biochemical testing has confirmed the diagnosis of galactosemia, sequencing of the GALT gene is available to identify private mutations.
The GALT gene maps to 9p13. Several disease-causing mutations are common in patients with classic galactosemia (G/G genotype). The most frequently observed is the Q188R classic mutation. This mutation accounts for 60% to 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 25% to 40% of the alleles in this population. The L195P mutation is observed in 5% to 7% of classical galactosemia. The Duarte mutation (N314D) is observed in 5% of the general United States population.
The above mutations, in addition to the LA variant, are included in GAL6/84366 Galactosemia Gene Analysis (6-Mutation Panel) and in GCT/84360 Galactosemia Reflex, Blood. See Galactosemia Testing Algorithm in Special Instructions for additional information. Refer to Galactosemia: Current Testing Strategy and Aids for Test Selection, Mayo Medical Laboratories Communique 2005 May;30(5) for more information regarding diagnostic strategy.
Second-tier test for confirming a diagnosis of galactosemia (indicated by enzymatic testing or newborn screening)
Carrier testing family members of an affected individual of known genotype (has mutations included in the panel)
Resolution of Duarte variant and LA variant genotypes
An interpretative report will be provided.
Results should be interpreted in the context of biochemical results.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This assay will not detect all of the mutations that cause galactosemia. Therefore, the absence of a detectable mutation(s) does not rule-out the possibility that an individual is a carrier of or affected with this disease.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
In rare cases, DNA alterations of undetermined significance may be identified.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Many disorders may present with symptoms similar to those associated with galactosemia. Therefore, biochemical testing is recommended to establish the diagnosis of galactosemia prior to DNA analysis.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Elsas LJ 2nd, Lai K: The molecular biology of galactosemia. Genet Med 1998 Nov-Dec;1(1):40-48
2. Kaye CI, Committee on Genetics, Accurso F, et al: Newborn screening fact sheets. Pediatrics 2006 Sep;118(3):e934-963
3. Novelli G, Reichardt JK: Molecular basis of disorders of human galactose metabolism: past, present, and future. Mol Genet Metab 2000 Sep-Oct;71(1-2):62-65