Galactosemia (Galactokinase Deficiency): GALK1 Gene Deletion/Duplication

Create a PDF of this page

Condition Description

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 [3]. Galactokinase-deficiency may present in the neonatal period with cataracts; no other clinical complications have been consistently associated with GALK-deficiency [2].

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 (IQ).

Visit www.ThinkGenetic.com for patient-friendly information on galactosemia.

Click here for the GeneReviews summary on this condition. Also, refer to the Comprehensive Galactosemia Panel for a disease overview.

References:
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.

Genes (1)

Indications

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.

Methodology

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.

Detection

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 [8], 4/4 mutations identified in 2 patients [9].
Analytical Sensitivity: ~99%Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Submit only 1 of the following specimen types

Preferred specimen type: Whole Blood

Type: Whole Blood

Specimen Requirements:

In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>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.

Type: Saliva

Specimen Requirements:

OrageneTM Saliva Collection kit (available through EGL) 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.

Special Instructions

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 outside of Emory Genetics Laboratory, please submit a copy of the sequencing report with the test requisition.

  • GALT and GALE Gene Sequencing for transferase deficient and epimerase deficient galactosemia
  • Comprehensive Galactosemia Panel includes: GALT enzyme activity, isozyme pattern, gal-1-P concentration
  • Urine Galactitol Concentration
  • Custom Diagnostic Mutation Analysis (KM) is available to family members if mutations are identified by sequencing.
  • Prenatal testing is available for known familial mutations only. Please call the Laboratory Genetic Counselor before collecting a fetal sample.

How to Order