Galactosemia Type II via the GALK1 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
1448 GALK1$650.00 81479 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, Kolosha et al. (2000) analyzed the GALK1 gene from thirteen probands with low levels of erythrocyte galactokinase activity. Causative variants were found in the homozygous or compound heterozygous state in all thirteen probands (100%). Additionally, Kalaydjieva et al. (1999) used DNA sequencing to analyze the GALK1 gene in eight galactokinase deficient Romani children, and found the same variant (c.82C>A, p.Pro28Thr) in the homozygous state in all eight (100%). Additionally, this same variant was identified in the heterozygous state in all unaffected family members.

Overall, the analytical sensitivity of this test is expected to be high because all pathogenic variants in the GALK1 gene reported to date are detectable via DNA sequencing.

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 GALK1$690.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity
To date, there have been no reported gross deletions or duplications in the GALK1 gene (Human Gene Mutation Database).

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Clinical Features
Galactosemia Type II is caused by a defect in galactose metabolism, resulting in an elevated level of total galactose and derivative metabolites. In the vast majority of affected patients, the only clinical and biochemical findings are bilateral cataracts, galactosemia and increased urinary galactitol. However, a few patients have been reported with intellectual disability or pseudotumor cerebri. The onset of symptoms is usually within the first weeks or months of life. This disorder is treated by restricting dietary intake of galactose and lactose, and if treatment is started early, symptoms are preventable or reversible. However, in cases where treatment is not begun until after cataracts have already formed, the damage may not be reversible by dietary restriction and surgery may be required (Fridovich-Keil and Walter 2014). 
In countries where newborn screening programs operate, such programs typically identify galactosemic individuals shortly after birth. However, in cases where the first round of screening is based on GALT enzyme activity alone, individuals with galactosemia type II rather than GALT-deficient classical galactosemia may be missed (Berry 2014; Fridovich-Keil and Walter 2014).
Galactosemia Type II is an autosomal recessive disorder, and GALK1 is the only gene in which defects are known to cause galactokinase deficiency (Fridovich-Keil and Walter 2014). To date, over 35 causative variants have been reported in the GALK1 gene (Kalaydjieva et al. 1999; Kolosha et al. 2000; Okano et al. 2001; Park et al. 2007; Stambolian et al. 1995; Human Gene Mutation Database). Roughly two-thirds are missense variants, although nonsense, frameshift and small insertion and deletion variants have also been reported. The variants are spread throughout the coding regions of GALK1, although they tend to be somewhat clustered near conserved functional regions in exons 1, 3 and 7 (Fridovich-Keil and Walter 2014).  The Pro28Thr variant has been reported to be a founder mutation in individuals of Romani and southeastern European descent (Kalaydjieva et al. 1999). The relatively mild Ala198Val variant has been found to be common in Japanese and Korean patients and has been termed the Osaka variant (Okano et al. 2001). The Gln382* variant has been reported to be common in patients from Costa Rica (Kolosha et al. 2000). No other pathogenic variants have been reported to be particularly common.

Galactosemia Type II is caused by defects in the galactokinase protein, which is encoded by the GALK1 gene. This enzyme is part of the galactose metabolism pathway in many organisms and performs the first step in the Leloir pathway, converting galactose to galactose-1-phosphate. While the phosphorylation reaction performed by galactokinase is reversible, the reaction equilibrium leans heavily in favor of galactose-1-phosphate formation (Berry 2014; Fridovich-Keil and Walter 2014). In the absence of galactokinase activity, galactose builds up and is converted to other metabolites, including galactitol, at a higher rate than normal. Excess galactitol accumulation in the lens of the eye leads to osmotic irregularities, which is thought to be the cause of cataract formation (Okano et al. 2001; Fridovich-Keil and Walter 2014).
Testing Strategy
This test involves bidirectional Sanger sequencing using genomic DNA of all coding exons of the GALK1 gene plus ~10 bp of flanking non-coding DNA on each side. 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.
Indications for Test
Patients identified as galactosemic via newborn screening or other biochemical testing, especially individuals with elevated total galactose, elevated urinary galactitol, normal GALT enzyme activity levels and decreased GALK enzyme activity levels, are good candidates for this test. Infants with bilateral cataracts that develop within the first weeks or months of life are also good candidates for this test (Berry 2014; Fridovich-Keil and Walter 2014). Lastly, family members of patients who have known GALK1 variants are candidates. We will also sequence the GALK1 gene to determine carrier status.


Official Gene Symbol OMIM ID
GALK1 604313
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Deficiency Of Galactokinase 230200

Related Tests

Epimerase Deficiency Galactosemia via GALE Gene Sequencing with CNV Detection
Galactosemia Type I via the GALT Gene
Galactosemia Type I via the GALT Gene, 5.5 kb Common Deletion


Genetic Counselors
  • 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
  • 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.
  • Human Gene Mutation Database (Bio-base).
  • Kalaydjieva L, Perez-Lezaun A, Angelicheva D, Onengut S, Dye D, Bosshard NU, Jordanova A, Savov A, Yanakiev P, Kremensky I, Radeva B, Hallmayer J, Markov A, Nedkova V, Tournev I, Aneva L, Gitzelmann R. 1999. A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies). Am. J. Hum. Genet. 65: 1299–1307. PubMed ID: 10521295
  • Kolosha V, Anoia E, Cespedes C de, Gitzelmann R, Shih L, Casco T, Saborio M, Trejos R, Buist N, Tedesco T, Skach W, Mitelmann O, Ledee D, Huang K, Stambolian D. 2000. Novel mutations in 13 probands with galactokinase deficiency. Hum. Mutat. 15: 447–453. PubMed ID: 10790206
  • Okano Y, Asada M, Fujimoto A, Ohtake A, Murayama K, Hsiao K-J, Choeh K, Yang Y, Cao Q, Reichardt JKV, Niihira S, Imamura T, Yamano T. 2001. A Genetic Factor for Age-Related Cataract: Identification and Characterization of a Novel Galactokinase Variant, “Osaka,” in Asians. Am J Hum Genet 68: 1036–1042. PubMed ID: 11231902
  • Park H-D, Bang Y-L, Park KU, Kim JQ, Jeong B-H, Kim Y-S, Song Y-H, Song J. 2007. Molecular and biochemical characterization of the GALK1 gene in Korean patients with galactokinase deficiency. Mol. Genet. Metab. 91: 234–238. PubMed ID: 17517531
  • Stambolian D, Ai Y, Sidjanin D, Nesburn K, Sathe G, Rosenberg M, Bergsma DJ. 1995. Cloning of the galactokinase cDNA and identification of mutations in two families with cataracts. Nat. Genet. 10: 307–312. PubMed ID: 7670469
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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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