CLIA #: 52D1027685 ● CAP #: 7185561

AU ID: 1407125 ● NPI: 1114140571

3700 Downwind Drive
Marshfield, WI 54449 USA
Phone: 715-387-0484 Fax: 715-384-3661

Glycogen Storage Disease Type IV via GBE1 Gene Sequencing (Test #225)

Brief Description of Clinical Features: Glycogen Storage Disease (GSD) Type IV (OMIM 232500), also known as
Andersen Disease, is a rare, severe disorder caused by a deficiency of glycogen branching enzyme encoded by the GBE1
gene. Clinical features for GSD Type IV vary widely. Some research groups bin patients into two groups: those
presenting with liver disease and those presenting with neuromuscular symptoms (see OMIM;
http://www.emedicine.com/ped/topic97.htm; Bao et al. J Clin Invest 97:941-948, 1996; and Bruno et al. Neurology
63:1053-1058, 2004). In most liver disease cases, failure to thrive is observed during the first 18 months.
Hepatosplenomegaly and liver cirrhosis then develop, leading to death by 5 years. Non-progressive hepatic forms have
also been described. The neuromuscular forms of the disease range from a lethal neonatal form with hypotonia, muscle
wasting and cardiomyopathy to an adult onset form, sometimes called Adult Polyglucosan Body Disease (APBD) (OMIM
263570) characterized by neurodegenerative features. For additional information, see the web sites for the Association for
Glycogen Storage Disease (www.agsdus.org) and the APBD Research Foundation (www.apbdrf.org).

Genetics: Both GSD Type IV and APBD are autosomal recessive disorders. Mutations in the GBE1 gene are the only
known cause of both of these disorders. About 20 different causative mutations have been reported. The mutations are
about equally split between missense and nonsense/frameshift. Mutations are located throughout the length of the gene.
APBD appears to be more common in people with Ashkenazi Jewish ancestry than other populations. Few connections
have been made between genotype and phenotype, although there are indications that some missense mutations may lead
to partial enzymatic activity and less severe phenotypes.

Description of This Particular Test: This test involves PCR amplification from genomic DNA and bidirectional
sequencing of all protein coding regions of the 16 GBE1 exons. We will perform full gene sequencing to identify carriers.
We will also sequence single exons or pairs of exons in the family members of patients with known mutations to
determine carrier status and in patients to confirm research results.

Indications for Test: All patients with symptoms of GSD Type IV are candidates for this test. Many of those tested will
have reduced glycogen branching activity determined by enzyme assay.

Sensitivity of Test: Sensitivity of this test has not been reported, but should be relatively high for patients with low
enzyme activity.

Turn Around Time: Maximum of 40 days, although many tests are completed in 2-3 weeks.
Specimen Requirements: See end of Requisition Form.

Price: Sequencing of all 16 GBE1 coding exons $ 990

CPT Codes:
Ascertainment x1 83890 $ 30 DNA Isolation x1 83891 $ 40
Amplification x16 83898 $ 310 Sequencing x16 83904 $ 460
Separation x1 83894 $ 60 Interpretation/Report x1 83912 $ 90
Single exon sequencing is available for $190 and sequencing of two exons for $340.

Accreditation Info. CLIA ID #: 52D1027685 (expires 1/18/11) (CAP#: 7185561, AU ID: 1407125 expires 12/20/10)

Contact for info: Dr. James Weber, www.preventiongenetics.com, jim.weber@preventiongenetics.com

Version 1.3 October 14, 2009