Galactosemia Confirmation with Reflex to Galt Gene Analysis
Label Mnemonic: GALCON
Epic Lab Code: LAB3194
Downtime Form: A-1a Miscellaneous Request
Commercial Mail-out Laboratory
5231 RCP
356-8593
Specimen(s):
Whole Blood
Specimen Instructions:
Patient's age is required.
Collection Medium:
Pink top tube 6 mL (K2-EDTA)
Minimum:
Preferred Minimum: 5.0 mL whole blood in a pink top (EDTA) tube.
Absolute Minimum: 2.0 mL whole blood in a pink top (EDTA) tube.
Delivery Instructions:
Submit specimen to laboratory as soon as possible after collection.
Turn Around Time:
4 days upon receipt at reference laboratory
Reference Range:
> or =24.5 nmol/h/mg of hemoglobin
Interpretive Data:
The laboratory provides an interpretation of the results, including galactose-1-phosphate uridyltransferase enzyme activity and genotype, 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 <24.5 nmol/h/mg of hemoglobin will be analyzed for the presence of 14 mutations associated with classic galactosemia, as well as the 2 variants (Duarte and Los Angeles). See Galactosemia Reflex Algorithm in Special Instructions for testing algorithm and additional information.

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 5 kb deletion is common in individuals of Ashkenazi Jewish descent. The Duarte mutation (N314D and -119_-116delGTCA) is observed in 5% of the general United States population. The rest of the mutations detected by this method (ie, D98N, S135L, T138M, M142K, F171S, Y209C, and Q344K) are all uncommon, but known to be recurrent in the general population.

A high proportion (20%) of patients with classic galactosemia have a private mutation. Since our assay does not investigate for the presence of private mutations, when GG, DG, or NG genotype is predicted by enzymatic studies and the current panel does not identify a mutation, molecular sequencing may be indicated.
Comments:
Please print, complete and submit the Informed Consent for Genetic Testing from Mayo Medical Laboratories with the specimen and the A-1a Miscellaneous Request or Epic Req.

Patient's age is required on request form for processing.

Useful for:
1) Diagnosis, carrier detection, and determination of genotype of
   galactose-1-phosphate uridyltransferase deficiency, the most common
   cause of galactosemia

2) Differentiating Duarte variant galactosemia from classic
   galactosemia

3) Confirming results of newborn screening programs

Preferred test to evaluate for possible diagnosis of galactosemia, 
routine carrier screening, and follow-up of abnormal newborn screening 
results. Comprehensive reflex test begins with quantitative galactose-1-
phosphate uridyltransferase (GALT) enzyme analysis (GALT/Galactose-1-
Phosphate Uridyltransferase [GALT], Blood). If quantitative GALT enzyme 
value is consistent with a diagnosis of or carrier status for 
galactosemia, DNA analysis of the GALT gene (GAL14/Galactosemia Gene 
Analysis [14-Mutation Panel]) is performed to detect 14 galactosemia 
alleles: -119_-116delGTCA, D98N, S135L, T138M, M142K, F171S, Q188R, 
L195P, Y209C, K285N, N314D, Q344K, c.253-2A>G, and 5 kb deletion.
Test Limitations:
This assay is not useful for monitoring dietary compliance by galactosemics, see GAL1P / Galactose-1-Phosphate (Gal-1-P), Erythrocytes.

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.

Many disorders may present with symptoms similar to those associated with galactosemia. Therefore, biochemical testing is performed to establish the diagnosis of galactosemia prior to DNA analysis.
Methodology:
Enzyme Reaction Followed by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
CPT Code:
Galactose-1-Phosphate Uridyltransferase (GALT), Blood
82775

Galactosemia Gene Analysis (14-Mutation Panel)
81401-GALT (galactose-1-phosphate uridylyltransferase) (eg, galactosemia), common variants (eg, Q188R, S135L, K285N, T138M, L195P, Y209C, IVS2-2A->G, P171S, del5kb, N314D, L218L/N314D