Test Directory

Test Code
1477
Test Name
Arterial Calcification, Generalized, Of Infancy, 2
CPT Codes
81479
Expected Turnaround Time
Typically 2 to 4 weeks from receipt of a sample in the laboratory. All cases involving ongoing pregnancies will be expedited.
Clinical Utility
Genetic analysis to provide a molecular diagnosis of this disorder. Recommended for individuals with a personal and/or family history of this disorder to ensure appropriate treatment and establish recurrence risk for family members.
Specimen and Container Info

Non-Prenatal Specimens

Preferred/Alternate

Specimen Type

Containers

Volume

Preferred Specimen Type

Whole Blood

Lavender Top (EDTA)

3 mL

Alternate Specimen Type

Genomic DNA

1.5 mL Tube

3 µg (at a concentration of at least 30 ng/µl), preferably in TE solution.

Alternate Specimen Type

Fibroblasts

T-25 Flasks

2 confluent T-25 flasks, filled to capacity

Alternate Specimen Type

Saliva (Whole blood is recommended for CNV)

DNA Self-Collection Kit or Oragene Saliva Collection Kit for Young Children

Follow kit instructions (www.dnagenotek.com)

Prenatal Specimens

Either specimen type below is acceptable.

Specimen Type

Containers

Volume

Cultured cells

T-25 Flasks

2 confluent T-25 flasks derived from amnio or CVS samples.

Genomic DNA

1.5 mL Tube

3 µg (at a concentration of at least 30 ng/µl), preferably in TE solution.

NOTE: For specimens from outside of North America, the preferred specimen type is Genomic DNA. HNL Genomics does not recommend shipping whole blood or cultured cells from any location other than the United States, Canada, or Mexico.

Transport Instructions
  • Transport at room temperature within 24 hours.
  • If the specimen cannot be transported to the lab within 24 hours, refrigerate for up to 72 hours.
  • Do not freeze or expose to extreme temperatures, refrigerate for up to 72 hours if cannot be transported to lab within 24 hours. 
Stability Requirements

Room Temperature

24 hours

Refrigerated

72 hours

Causes for Rejection
  • Improperly labeled specimen (minimum of two patient identifiers)
  • Inappropriate specimen type
  • Incomplete or incorrect test request form
  • Insufficient volume
  • Specimen has leaked in transit
  • Specimen without a test order
Methodology
Next Generation Sequencing and Copy Number Variation Analysis
Performing Location
Genomics - Snowdrift
Alternate Names
  • GACI
  • GACI1
  • GACI2
Description

Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder that is frequently fatal in infancy. This disorder is characterized by calcification of large and medium sized arteries and myointimal proliferation resulting in arterial stenosis. In some affected individuals the disease is detected prenatally. Most patients die in early infancy due to myocardial infarction or congestive heart failure.  GACI1 (MIM 208000) is caused by loss of function mutations in the ectonucleotide pyrophosphatase / phosphodiesterase 1 gene (ENPP1) and GACI2 (MIM 614473) is caused by loss of function mutations in the ATP-binding cassette, subfamily c, member 6 gene (ABCC6). ENPP1 is a transmembrane glycoprotein involved in the regulation of soft issue calcification and bone and joint cartilage mineralization via the generation of pyrophosphate (PPi). PPi is a physiological inhibitor of hydroxyapatite formation and a suppressor of chondrogenesis. ABCC6 is an ATP-binding cassette transmembrane transporter whose exact role in arterial and tissue calcification remains elusive. The GACI phenotype caused by ENPP1 or ABCC6 mutations may be clinically indistinguishable. Mutations in ENPP1 also cause some cases of autosomal recessive hypophosphatemic rickets (ARHR2; MIM 613312). In at least one family an identical ENPP1 mutation has been shown to cause hypophosphatemic rickets in a father and generalized arterial calcification of infancy in his son. Additionally, mutations in ABCC6 cause autosomal recessive pseudoxanthoma elasticum (PXE; MIM 264800), a multisystem disorder characterized by findings in the skin, eyes and cardiovascular system. Interestingly, a patient with GACI2 and hypophosphatemic rickets has been described and several patients with GACI1 and pseudoxanthoma elasticum have been reported suggesting that mutations in both ENPP1 and ABCC6 can cause a spectrum of clinical features including GACI, pseudoxanthoma elasticum, and hypophosphatemic rickets.

Testing Schedule
Monday-Friday
Genes
ABCC6
MIM
614473
Disease Group
Cardiovascular Disorders, Skin