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HelpTest Code SOFT: Z0060 Galactose-1-Phosphate Uridyltransferase Biochemical Phenotyping, Erythrocytes
Additional Codes
| Ordering Mnemonic | Mayo Test ID |
|---|---|
| HOM: GPUT GENOTYPING | GALTP |
Reporting Name
Gal-1-Phos Urdyltrns Phenotype,RBCUseful For
Determining the biochemical phenotype for galactosemia when enzymatic and molecular results are incongruent
Additional Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| GALT | Gal-1-P Uridyltransferase, RBC | Yes | Yes |
Testing Algorithm
A quantitative galactose-1-phosphate uridyltransferase (GALT) level is used in addition to the isoelectric focusing for accurate interpretation. If recent GALT test results are not provided, GALT testing will be automatically performed at an additional charge. However, if previous GALT results are provided, GALT testing will be canceled.
For more information see Galactosemia Testing Algorithm.
Method Name
Isoelectric Focusing
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
Whole Blood EDTAOrdering Guidance
The preferred test to evaluate for possible diagnosis of galactosemia, routine carrier screening, and follow-up of abnormal newborn screening results is GCT / Galactosemia Reflex, Blood.
For monitoring of dietary compliance, order GAL1P / Galactose-1-Phosphate, Erythrocytes.
Necessary Information
Patient's age is required.
A quantitative galactose-1-phosphate uridyltransferase level (GALT / Galactose-1-Phosphate Uridyltransferase, Blood) is required for accurate interpretation.
Biochemical Genetics Patient Information (T602) is recommended, but not required, to be filled out and sent with the specimen to aid in the interpretation of test results.
Specimen Required
Multiple whole blood tests for galactosemia can be performed on 1 specimen. Prioritize order of testing when submitting specimens. For a list of tests that can be ordered together see Galactosemia-Related Test List.
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Specimen Minimum Volume
2 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Whole Blood EDTA | Refrigerated (preferred) | 28 days | |
| Ambient | 14 days |
Reject Due To
| Gross hemolysis | Reject |
Special Instructions
Reference Values
An interpretative report will be provided.
Day(s) Performed
Pre-analytical processing: Monday through Saturday
Assay performed: Twice per month, Thursday
CPT Code Information
82664
82775
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| GALTP | Gal-1-Phos Urdyltrns Phenotype,RBC | 33780-8 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 80341 | Gal-1-Phos Urdyltrns Phenotype,RBC | 33780-8 |
| 34524 | Reviewed By | 18771-6 |
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.Disease States
- Galactosemia
Clinical Information
Galactosemia is an autosomal recessive disorder that results from a deficiency of any 1 of the 4 enzymes catalyzing the conversion of galactose to glucose: galactose-1-phosphate uridyltransferase (GALT), galactokinase (GALK), uridine diphosphate galactose-4-epimerase (GALE), and galactose mutarotase (GALM). GALT deficiency is the most common cause of galactosemia and is often referred to as classic galactosemia. The complete or near-complete deficiency of GALT enzyme is life threatening if left untreated. Complications in the neonatal period include failure to thrive, liver failure, sepsis, and death.
Galactosemia is treated by a galactose-restricted diet, which allows for rapid recovery from the acute symptoms and a generally good prognosis. Despite adequate treatment from an early age, individuals with galactosemia remain at increased risk for developmental delays, speech problems, and abnormalities of motor function. Female patients with galactosemia are at increased risk for premature ovarian failure. Based upon reports by newborn screening programs, the frequency of classic galactosemia in the United States is approximately 1 in 30,000, although literature reports range from 1 in 10,000 to 1 in 60,000 live births.
Duarte-variant galactosemia (compound heterozygosity for the Duarte variant, N314D, and a classic variant) is generally associated with higher levels of enzyme activity (5%-20%) than classic galactosemia (<5%); however, this may be indistinguishable by newborn screening assays. Previously, it was unknown whether children with Duarte-variant galactosemia were at an increased risk for adverse developmental outcomes due to milk exposure and were often treated with a low galactose diet during infancy. More recently, the outcomes data suggest a lack of evidence for developmental complications due to milk exposure, therefore treatment recommendations remain controversial. The Los Angeles variant, which consists of N314D and a second variant, L218L, is associated with higher levels of GALT enzyme activity than the Duarte-variant allele.
In general, molecular genetic analysis (GALZ / Galactosemia, GALT Gene, Full Gene Analysis, Varies) is typically performed to determine the specific genotype. If the enzymatic and molecular results are incongruent, biochemical phenotyping may be beneficial to help clarify results to determine a treatment strategy and recurrence risks.
For more information see Galactosemia Testing Algorithm.
Interpretation
Different banding patterns obtained by isoelectric focusing of galactose-1-phosphate uridyltransferase (GALT) can be consistent with classic galactosemia, carrier status for a disease-causing GALT variant, compound heterozygosity, or a normal biochemical phenotype. The banding pattern is interpretated in the context of the separately measured GALT activity.
Cautions
A more comprehensive interpretation can be provided when parental specimens are also submitted for testing.
The results of testing performed in erythrocytes, including analysis of enzymes, biochemical phenotyping, or galactose-1-phosphate, are invalid following a transfusion.
Clinical Reference
1. Berry GT. Classic galactosemia and clinical variant galactosemia. In: Adam MP, Feldman J, Mirzaa GM, et al. eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated March 11, 2021. Accessed September 12, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1518/
2. Walter JH, Fridovich-Keil JL. Galactosemia. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed September 12, 2024. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=%20225081023
3. Carlock G, Fischer ST, Lynch ME, et al. Developmental outcomes in Duarte galactosemia. Pediatrics. 2019;143(1):e20182516. doi:10.1542/peds.2018-2516
4. Anderson S. GALT deficiency galactosemia. MCN Am J Matern Child Nurs. 2018;43(1):44-51. doi:10.1097/NMC.0000000000000388
Method Description
Isoelectric focusing is used to resolve the isoenzymes of galactose-1-phosphate uridyltransferase (GALT). The band patterns, when used in conjunction with a quantitative GALT result, can be used to predict the GALT phenotype of an individual.
In isoelectric focusing, a pH gradient is established across an agarose gel by adding a select mixture of amphoteric molecules to the gel and applying an electric field to the gel. Each protein (isoenzyme) has its own unique isoelectric point, a pH at which the net charge of the protein is equal to zero. Therefore, if a protein is applied to the gel, it will migrate through the pH gradient in the gel until it reaches its isoelectric point. There the protein will stop and "focus" into distinct bands.
In this procedure, a red blood cell hemolysate is focused on a 5% agarose gel containing ampholytes of a 5 to 7 pH range. The isoenzyme bands are then visualized by applying a substrate mixture that results in a series of reactions (shown below). The final product, reduced nicotinamide adenine dinucleotide phosphate (NADPH), is stained a blue-violet color when it reacts with phenazine methosulfate and 3-(4-5 dimethylthiazol-2-yl) I-2,5-diphenyltetrazolium bromide.(Shin YS, Niedermeier HP, Endres W, Schaub J, Weidinger S. Agarose gel isoelectrofocusing of UDP-galactose pyrophosphorylase and galactose-1-phosphate uridyltransferase. Developmental aspect of UDP-galactose pyrophosphorylase. Clin Chim Acta. 1987;166[1]:27-35, modified to acrylamide as described by Leclerc P, Forest JC. Electrophoretic determination of isoamylases in serum with commercially available reagents. Clin Chem. 1982;28:37-40; Cowan T, Pasquali M. Laboratory investigations of inborn errors of metabolism. In: Sarafoglou K, Hoffman GF, Roth KS, eds. Pediatric Endocrinology and Inborn Errors of Metabolism. 2nd ed. McGraw-Hill; 2017:1139-1158)
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GALT |
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Gal-1-P + UDP-Glu |
-------------> |
UDP-Gal + Glu-1-P |
|
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Phosphoglucomutase |
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Glu-1-P + Glu-1-6 diP |
-------------> |
Glu-1-6 diP + Glu-6-P |
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Glu-6-P-Dehydrogenase |
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Glu-6-P + NADP |
-------------> |
Ribose-5-P + CO2 + NADPH |
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NADPH + MTT + PMS |
-------------> |
Blue Violet Stain |
Report Available
4 to 17 daysSpecimen Retention Time
Processed RBC: 2 monthsForms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. Biochemical Genetics Patient Information (T602) is recommended.
3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.