GeneDx
207 Perry Parkway
Gaithersburg, MD 20877
Phone: 301-519-2100
Fax: 301-519-2892
E-mail: genedx@genedx.com
www.genedx.com
Test Information Sheet
GK Gene Analysis in Glycerol Kinase Deficiency
Mendelian Inheritance in Man Numbers: 307030 – Glycerol Kinase Deficiency; 300474 – GK gene
Clinical features:
Glycerol kinase deficiency (GKD) is an X-linked disorder characterized by elevated plasma or urine glycerol.
It may occur as an isolated form caused by mutation of the GK gene alone or as part of a contiguous gene
syndrome involving the DAX1 and DMD genes on Xp21.3. Individuals with isolated GKD may be
asymptomatic or symptomatic with episodes of vomiting, acidosis and lethargy that may progress to coma or
CNS crisis. Phenotypic variability occurs even within families.1 Symptomatic individuals usually present with
signs of hypoglycemia, ketoacidosis, and/or seizures. Patients who are symptomatic in childhood may
become symptom free. Asymptomatic patients are often identified through hyperlipidemia testing when they
are mistaken as having hypertriglyceridemia, as elevated plasma glycerol concentrations can erroneously
result in overestimation of plasma triglycerides. Isolated GKD has also been found in children with
dysmorphic features and mental retardation; however, at this time, it is not clear whether or not these features
are related to GKD alone.2,3 Individuals with GKD as part of the Xp21.3 contiguous gene syndrome also
have features of congenital adrenal hypoplasia and/or Duchenne muscular dystrophy.
Inheritance pattern: X-linked
Genetics and biochemical features:
Isolated GKD is caused by mutations in the GK gene that encodes the glycerol kinase enzyme that catalyses
the phosphorylation of dietary glycerol to glycerol-3-phosphate, which is used in the synthesis of lipids.
Deficient glycerol kinase activity results in elevated urine and plasma glycerol. Elevated plasma glycerol
concentrations can mistakenly result in an overestimation of plasma triglycerides, known as
pseudohypertriglyceridemia. The GK gene is located on chromosome Xp21.3 and has 21 exons. Individuals
with GKD as part of the Xp21.3 contiguous gene syndrome may also have biochemical findings related to
congenital adrenal hypoplasia and/or Duchenne muscular dystrophy such as hypoglycemia, hyponatraemia,
hyperkalaemia and elevated creatine kinase.
Reasons for referral:
1. Confirmation of biochemical diagnosis
2. Carrier testing
3. Genetic counseling
4. Prenatal diagnosis in at risk pregnancies
Test method:
Mutation analysis of the GK gene is performed on genomic DNA from the submitted specimen using bidirectional sequence analysis of the coding exons and corresponding intron/exon boundaries. In addition, if
no mutation is found by sequencing, targeted array CGH analysis with exon-level resolution (ExonArrayDx)
is available for females to evaluate for a deletion or duplication of one or more exons of this gene. Mutations
found in the first person of a family to be tested are confirmed by repeat analysis using sequencing, restriction
fragment analysis or another appropriate method.
Information Sheet on GK deficiency
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GeneDx 10/10
Test sensitivity:
In a series of small studies of males with confirmed isolated GKD, a GK mutation was identified in all
individuals.2, 3, 4, 5, 6, 7
Mutation spectrum:
GK mutations consist of missense, nonsense, splice site, small deletions/insertions and large deletions. An
N288D missense mutation in the GK gene has been identified in individuals from the Saguenay Lac-St.-Jean
region of Quebec with severe hyperglycerolemia but otherwise no frequent mutations have been reported.5
Genotype-phenotype correlations have not been established.2, 4, 8
Specimen Requirements and Shipping/Handling:
 Blood: A single tube with 1-5 mL whole blood in EDTA (1-2mL for infants). Ship overnight at ambient
temperature, using a cool pack in hot weather. Specimens may be refrigerated for one week prior to
shipping.
 Buccal Brushes: Can be used as an alternative to blood for GK sequencing only. Gene
deletion/duplication testing requires submission of a venous blood sample. When sending a

buccal sample, use a GeneDx buccal kit (others not accepted). Submit by mail. Buccal brushes are not
accepted on children under 6 months of age.
Prenatal Diagnosis: 20 mL amniotic fluid, 5 mg CVS, or 2 T25 flasks. Ship overnight at ambient
temperature, using a cool pack in hot weather. Call to discuss requirements for parental blood. Keep
backup cultures.
Required Forms:
Sample Submission (Requisition) Form – complete all pages
Payment Options Form or Institutional Billing Instructions
Prices and Turn-Around Time - Fees are subject to change without notice:
Test# 438 Mutation detection in a new patient
$ 2220
Test # 906: GK Deletion/duplication testing (ExonArrayDx)
$ 500
Test# 901 Testing of a relative for one (two) specific
known mutations
$ 350 ($500)
Test# 902 Prenatal diagnosis for a specific known mutation
$ 2000
(including maternal cell contamination studies)
Approx. 4 weeks
Approx. 4 weeks
Approx. 2-3 weeks
Approx. 2 weeks
CPT codes for mutation detection in a new patient - All codes and units apply:
#438 GK Sequencing
83891
83898
83894
83904
83892
83912
x
x
x
x
x
x
TOTAL
19
38
19
38
2
2
units = $
units = $
units = $
units = $
units = $
units = $
# 906 GK Deletion/Duplication Testing (ExonArrayDx)
220
730
220
950
40
60
83891 x 2 units = $ 12
88386 x 1 units = $ 488
$ 2220
TOTAL
ICD9 codes that might apply to new patients having this diagnostic test:
Other specified disorder of metabolism
$ 500
277.8
References: 1. Hellerud et al., (2003) Clin Chem Lab Med 41:46-55. 2. Hellerud et al., (2004) Acta Paediatr 93:911-921. 3.
Sjarif et al., (2004) Eur J Hum Genet 12:424-432. 4. Sargent et al., (2000) J Med Genet 37:434-441. 5. Gaudet et al.,
(2000) Am J Hum Genet 66:1558-1568. 6. Walker et al., (1996) Am J Hum Genet 58:1205-1211. 7. Sjarif et al., (1998)
J Med Genet 35:650-656. 8. Dipple et al., (2001) Hum Genet 109:55-62.
Information Sheet on GK deficiency
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GeneDx 10/10