Pantothenate Kinase-Associated Neurodegeneration

Clinical Characteristics
Ocular Features: 

Clinically evident retinal degeneration is present in a significant number (25-50%) of individuals.  However, when combined with ERG evidence the proportion rises to 68%.  When present it occurs early and one series reported that it is unlikely to appear later if it was not present early in the course of the neurodegeneration.  Some patients have a fleck-like retinopathy.  Optic atrophy may be present in advanced cases.

Systemic Features: 

This is a disorder primarily of the basal ganglia resulting from progressive damage secondary to iron accumulation.  There is an early onset classic form with symptoms of extrapyramidal disease beginning in the first decade of life and rapid progression to loss of ambulation in about 15 years.  Others with atypical disease may not have symptoms until the second or third decades.  Clumsiness, gait disturbance, and difficulty with tasks requiring fine motor coordination are common presenting symptoms.  Motor tics are often seen.  Dysarthria, dystonia, rigidity and corticospinal signs are often present early as well.  Swallowing difficulties may be severe sometimes leading to malnutrition.  Cognitive decline and psychiatric disturbances such as obsessive-compulsive behavior and depression may follow.  Independent ambulation is lost in the majority of patients within one to two decades.    Brain MRIs show an ‘eye of the tiger’ sign with a specific T2- weighted pattern of hyperintensity within the medial globus pallidus and the substantia nigra pars reticulata.


Iron accumulation in the basal ganglia resulting from homozygous mutations in the PANK2 gene (20p13-12.3) encoding a pantothenate kinase leads to the classic form of this autosomal recessive disorder. 

This is the most common of several diseases of neurodegeneration with iron accumulation in the brain known collectively as NBIAs.  The group is genetically heterogeneous with many overlapping features.  Mutations in PLA2G6 cause NBIA2A (256600) and NBIA2B (610217) while mutations in a FLT gene cause NBIA3 (606159). The latter does not have apparent eye signs.

Treatment Options: 

Pharmacologic treatment is aimed at alleviation of specific symptoms such as dystonia and spasticity.  Some symptoms may improve with deep brain stimulation.

Article Title: 


Gregory A, Polster BJ, Hayflick SJ. Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J Med Genet. 2009 Feb;46(2):73-80. Review.

PubMedID: 18981035

Pellecchia MT, Valente EM, Cif L, Salvi S, Albanese A, Scarano V, Bonuccelli U, Bentivoglio AR, D'Amico A, Marelli C, Di Giorgio A, Coubes P, Barone P, Dallapiccola B. The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration. Neurology. 2005 May 24;64(10):1810-2.

PubMedID: 15911822

Hayflick SJ, Westaway SK, Levinson B, Zhou B, Johnson MA, Ching KH, Gitschier J. Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N Engl J Med. 2003 Jan 2;348(1):33-40.

PubMedID: 12510040