• Test Code:
  • Department:
    Molecular Genetics
  • Test Synonyms:
    Hallervorden-Spatz SyndromePANK2NBIA
  • CPT Code(s):

Pantothenate kinase-associated neurodegeneration (PKAN) (previously known as Hallervorden-Spatz syndrome) is a progressive neurodegenerative disorder with brain iron accumulation.  Symptoms include progressive dystonia, dysarthria, rigidity, and retinitis pigmentosa.  Classical PKAN has its onset in the first decade of life; atypical PKAN presents with later onset and slower disease progression.  The disease is autosomal recessive and is caused by mutations in the pantothenate kinase 2 (PANK2) gene.  

Reasons for Referral:

  • Confirmation of clinical diagnosis in patients with classical or atypical PKAN.
  • Carrier testing of family members of PKAN patients.
  • Prenatal diagnosis.


The test has two components:

Component 1: Sequencing using either Sanger Sequencing or Next-Generation Sequencing. Sanger Sequencing:  Sequencing of PANK2 is carried out by amplification of all exons and intron/exon boundaries followed by bi-directional Sanger sequencing.  The sensitivity of full gene sequencing is estimated to be approximately 99% for single nucleotide substitutions and small insertions/deletions.  All nucleotide changes are analyzed within the context of current databases and literature to predict pathogenicity.

NGS:  Next generation sequencing will analyze the exons or coding regions of PANK2 using Illumina NextSeq 500 technology.  Samples are prepared using hybridization probes to enrich exonic regions.  Promoter, intronic, etc. regions are not assessed on our assay, but may contain variants that impact gene function.

Component 2: Large deletions and duplications are assessed using either multiplex ligation-dependent probe amplification (MLPA) or by a customized CytoSure “exon-centric” array (Oxford Gene Technology).  The targeted array has enhanced probes targeted to the exonic regions of PANK2.  The arrays are run using Agilent SureScan technology.

 >98% detection rate in patients with eye-of-the-tiger sign on MRI.

 Test reporting follows the American College of Medical Genetics (ACMG) guidelines.

Specimen Requirements:

Blood: EDTA or ACD (Solution A or B):

  • Adult:  5 mL
  • Child:  5 mL
  • Infant:  2-3 mL


  • Direct Amniotic Fluid (10-20mL)
  • Direct CVS
  • Cultured Amnio or CVS (2-T25 flasks)

DNA: 10µg at a minimum of 100ng/µL

Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:

  • Maternal cell rule-out testing will be performed on all prenatal specimens received. Please provide maternal blood in addition to the fetal specimen. Additional charges apply for the maternal cell rule-out test.
  • All genetic testing performed on Direct CVS or Amniotic Fluid specimens will be confirmed on cell cultures prepared by Knight Diagnostic Laboratories. Cell cultures will be prepared from the specimen received. Additional charges apply for confirmatory testing.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):


Turn Around Time:

14 – 21 days

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.


Additional Info:

Prior to any genetic testing we recommend genetic counseling.  Please contact Client Services at (855) 535-1522 for forms and information about prenatal diagnostic testing.