Galactosemia (Galactokinase Deficiency): GALK1 Gene Deletion/Duplication
Test Code: 4148
Turnaround time: 3 weeks
Galactokinase (GALK) deficiency is one of the three known forms of galactosemia, along with galactose-1-phosphate uridylyltransferase (GALT) deficiency (classic galactosemia) and UDP-galactose-4′-epimerase (GALE) deficiency [1-2]. GALK deficiency is an autosomal recessive disorder characterized by an elevation of blood galactose concentration and diminished galactose-1-phosphate concentration, leading to production of alternative metabolic products such as galactitol . Galactokinase-deficiency may present in the neonatal period with cataracts; no other clinical complications have been consistently associated with GALK-deficiency .
GALK deficiency should be considered in individuals with cataracts, elevated red cell galactose, galactosuria, or elevated urinary galactitol and normal GALT enzyme activity. GALK activity is used to rule-out variant galactosemia due to galactokinase deficiency which should not be confused with classical galactosemia secondary to GALT deficiency, or epimerase-deficiency galactosemia secondary to GALE deficiency. The vast majority of patients with biochemical diagnosis of GALK deficiency have mutations in the GALK1 (17q25) gene [4-6]. Gene sequence analysis is available to test for mutations in the GALK1 gene in patients with a biochemical diagnosis of GALK deficiency (test code: 9543).
1. Fridovich-Keil JL. Galactosemia: the good, the bad, and the unknown. J Cell Physiol 2006, 209(3):701-5.
2. Holton et al. Galactosemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease. McGraw- Hill, New York, pp. 1559-1561 (2001).
3. Gitzelmann R. Deficiency of erythrocyte galactokinase in a patient with galactose diabetes, Lancet 2:670-671, 1965.
4. Sangiuolo et al. Biochemical Characterization of Two GALK1 Mutations in Patients with Galactokinase Deficiency Hum Mutat 2004 Apr;23(4):396-403
5. Park et al. Molecular and biochemical characterization of the GALK1 gene in Korean patients with galactokinase deficiency. Mol Genet Metab. 2007. 91:234-8
6. Timson and Reece. Functional analysis of disease-causing mutations in human galactokinase Eur J Biochem. 2003. 270:1767-74
7. Thoden and Holden. The Molecular Architecture of Human N-Acetylgalactosamine Kinase. J Biol Chem 280(38):32784-32791, 2005.
8. Kolosha et al. Novel mutations in 13 probands with galactokinase deficiency. Hum Mutat 2000;15(5):447-53.
This test is indicated for:
- Individuals with elevated blood galactose but with normal GALT and GALE enzyme activities.
- Carrier testing for individuals with a family history of GALK deficiency.
Detection is limited to duplications and deletions. Array CGH will not detect point mutations or intronic mutations.
Please note that a “backbone” of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off- target copy number variants causative of disease may be identified that may or may not be related to the patient’s phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.
The vast majority of patients with clinical and biochemical diagnosis will have an abnormal DNA test. Clinical Sensitivity: 26/26 mutations identified in 13 patients , 4/4 mutations identified in 2 patients .
Analytical Sensitivity: ~99%Results of molecular analysis must be interpreted in the context of the patient’s clinical and/or biochemical phenotype.
Submit only 1 of the following specimen types
* Preferred specimen type: Whole Blood
Type: Whole Blood
In EDTA (purple top) or ACD (yellow top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
Submit copies of diagnostic biochemical test results with the sample. Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed by another third party provider, please submit a copy of the sequencing report with the test requisition.
• GALT and GALE Gene Sequencing for transferase deficient and epimerase deficient galactosemia
• Custom Diagnostic Mutation Analysis (test code: 6875) is available to family members if mutations are identified by sequencing.