Those with PKAN are deficient or completely lacking pantothenate kinase 2 (PANK2) activity. PANK2 deficiency is thought to cause accumulation of N-pantothenoyl-cysteine and pantetheine, which may cause cell toxicity directly or via free radical damage as chelators of iron. Deficient pantothenate kinase 2 is also predicted to result in coenzyme A (CoA) depletion and defective membrane biosynthesis in those tissues in which this is the major pantothenate kinase or in tissues with the greatest CoA demand.
PANK2 encodes a 1.85-kb transcript that is derived from seven exons spanning just over 35 Mb of genomic DNA on chromosome 20.
PKAN is inherited in an autosomal recessive manner. Diagnostic testing approaches may include single-gene testing, gene-targeted testing with specialized panels or exome or genome sequencing depending on the phenotype.
PANK2