Galactosemia Type I via the GALT Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
201 GALT$650.00 81406 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

Using DNA sequencing, Bosch et al. (2005) reported detection of 91% of causative variants in 106 consecutive galactosemia patients. Similarly, Kozák et al. (2000) reported detection of 96% of causative variants in 37 patients. More recently, Boutron et al. (2012) reported detection of 99% of causative variants in a cohort of 210 French families using direct sequencing.

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 GALT$990.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Sensitivity

While the great majority of GALT variants are expected to be detected via gene sequencing, several exonic or whole-gene deletions have been reported (Human Gene Mutation Database). In general, these deletions have been observed in a single patient, although a ~5.5 kb complex deletion is common in those of Ashkenazi Jewish descent (Barbouth et al. 2006; Coffee et al. 2006; Berry 2014). These types of copy number changes are expected to be detectable via gene-specific array CGH. The specific Ashkenazi Jewish ~5.5 kb deletion can also be detected by our PCR-based deletion test.

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Clinical Features

Galactosemia is a defect in the metabolism of galactose resulting in elevated levels of galactose and derivatives such as galactose-1-phosphate and galactitol. Severity of this disorder is quite variable, though it is generally categorized into three groups based on patient phenotype (Berry 2014). The first is the most severe “classic” form with onset in early infancy, and is characterized by feeding difficulties, vomiting, diarrhea, jaundice, cataracts, hypotonia, hepatomegaly and sepsis. If the amount of lactose in the diet is not reduced in the first days of life, these symptoms progress to death. Even in surviving patients, ovarian failure and lifelong speech and cognitive disabilities are expected (Berry 2014; Fridovich-Keil and Walter 2014). The second phenotypic category is termed "clinical variant" galactosemia, which also presents early in infancy and is more common in African Americans and native Africans in South Africa (Crushell et al. 2009; Berry 2014; Fridovich-Keil and Walter 2014). These patients tend to present with feeding difficulties, which may include failure to thrive, and hepatocellular damage, such as cirrhosis and bleeding. In these patients, if a lactose-restricted diet is implemented within the first days of life, the severe neonatal complications are typically prevented and the patients do not appear to be at risk for long-term complications (Berry 2014). The third phenotypic category is termed "biochemical variant galactosemia", the most common form of which is "Duarte variant galactosemia". Biochemical variant galactosemia is currently not thought to result in clinical disease in most patients (Berry 2014; Fridovich-Keil et al. 2014).

Today in wealthy nations, nearly all cases of classic galactosemia are detected through routine neonatal screening. However, it may be more difficult to detect patients with clinical and biochemical variant galactosemias because the galactose levels in such patients is not as high as in classic galactosemia patients, and results of breath testing may be normal (Berry 2014). In situations where the activity of the GALT enzyme is always tested or the patient is fed enough lactose, clinical and biochemical variant galactosemias should be detectable (Berry 2014; Fridovich-Keil et al. 2014).


Galactosemia is an autosomal recessive disorder. Pathogenic variants in the GALT gene are the primary genetic cause of galactosemia. Relatively small numbers of cases are caused by pathogenic variants in the GALK1 (galactokinase) and GALE (UDPgalactose-4’-epimerase) genes. GALT encodes the enzyme galactose-1-phosphate uridyltransferase. Over 300 causative GALT variants have been reported to date (Human Gene Mutation Database; ARUP GALT Database at Roughly 70% of these variants are missense, although frameshift, nonsense, splicing, small insertions and deletion variants and gross deletions have all been reported. The Gln188Arg variant is the most common cause of classic galactosemia, comprising up to 50% of all causative alleles in U.S. classic galactosemia patients and higher fractions among patients with western European ancestry (Berry 2014). Other common variants associated with classic galactosemia are the Lys285Asn and Leu195Pro missense variants, and a 5.5 kb complex deletion common in individuals of Ashkenazi Jewish descent. The Ser135Leu variant is particularly common among patients with African ancestry and is associated with clinical variant galactosemia (Suzuki et al. 2001; Crushell et al. 2009), whereas a 4-bp deletion in the GALT promoter, termed c.-119_-116delGTCA or D2 allele, is currently considered to be the main cause of Duarte variant galactosemia (Berry 2014). The Asn314Asp missense variant is usually found on the D2 allele together with the c.-119_-116delGTCA promoter variant, but as this missense variant also occurs on functionally normal GALT alleles, it is no longer considered to be a contributing factor to Duarte variant galactosemia (Berry 2014).

Testing for the 5.5 kb GALT deletion is available separately.

Testing Strategy

This test involves bidirectional DNA sequencing of all 11 exons of the GALT gene. The full coding region of each exon plus ~10 bp of flanking non-coding DNA on either side are sequenced. If specifically requested, we will sequence exon 6, containing the common Gln188Arg variant, first before proceeding to the rest of the gene. Our test covers the 4 bp deletion in the promoter region upstream of exon 1 (c.-119_-116 delGTCA) that has been shown to decrease enzyme activity in the Duarte allele (Elsas et al. 2001; Berry 2014). We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results. If desired, testing for the 5.5 kb GALT deletion common in the Ashkenazi Jewish population is available separately (Test #2310).

Indications for Test

All patients with reduced galactose-1-phosphate uridyltransferase activity are candidates for this test. We will also sequence the GALT gene to determine carrier status.


Official Gene Symbol OMIM ID
GALT 606999
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Galactosemia 230400

Related Test

Galactosemia Type I via the GALT Gene, 5.5 kb Common Deletion


Genetic Counselors
  • Barbouth D. et al. 2006. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 8: 178-82. PubMed ID: 16540753
  • Berry GT. 2014. Classic Galactosemia and Clinical Variant Galactosemia. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301691
  • Bosch A.M. et al. 2005. Human Mutation. 25: 502. PubMed ID: 15841485
  • Boutron et al. 2012. Molecular Genetics and Metabolism. 107:438-447 PubMed ID: 22944367
  • Coffee B. et al. 2006. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 8: 635-40. PubMed ID: 17079880
  • Crushell E. et al. 2009. Journal of Inherited Metabolic Disease. 32:412-5. PubMed ID: 19418241
  • Elsas L.J. et al. 2001. Molecular Genetics and Metabolism. 72: 297-305. PubMed ID: 11286503
  • Fridovich-Kei J.L. et al. 2014. Duarte Variant Galactosemia. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 25473725
  • Fridovich-Keil J.L., Walter J.H. 2014. Galactosemia. In: Valle D, Beaudet A.L., Vogelstein B, et al., editors. New York, NY: McGraw-Hill. OMMBID.
  • Kozák L. et al. 2000. Human Mutation. 15: 206. PubMed ID: 10649501
  • Suzuki M. et al. 2001. Human Genetics. 109: 210-5. PubMed ID: 11511927
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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