Pantothenate kinase-associated neurodegeneration (Hallervorden-Spatz syndrome)

Eur J Paediatr Neurol. 2002;6(5):243-7. doi: 10.1053/ejpn.2002.0606.

Abstract

The arguments over the nomenclature of the syndrome are reviewed. Ethical considerations favour replacing the present eponyms with the title of panthothenate kinase-associated neurodegeneration (PKAN), now that more is known about the cause of the condition. The symptoms and signs of the syndrome are described, and these can present from infancy to adult life. Dystonia, involuntary movements and spasticity are prominent causes of disability. If the onset is delayed the presentation can be unusual. Tests that can help in diagnosis are reviewed, especially the "eye of the tiger" revealed by magnetic resonance imaging scanning. Death usually occurs about 10 years after the onset, but the course may be more prolonged. The findings on autopsy are also considered, with the typical findings of iron pigment deposits and axonal spheroids. Then the causes are discussed. Once the responsible gene PANK2 had been discovered on chromosome 20 it was found that this encoded for pantothenate kinase which is essential for the synthesis of coenzyme A from pantothenate; and this is integral to fatty acid synthesis and energy metabolism. Also this can lead to a concentration of cysteine in the basal ganglia, and then to an accumulation of iron in these areas. The cysteine-iron complex will result in tissue damage by promoting oxidative stress, as in some other neurodegenerative diseases. The syndrome of PKAN can therefore be identified as a disorder of pantothanate, vitamin B5, metabolism. Infantile neuroaxonal dystrophy is briefly described as there have been suggestions that it is a variety of PKAN, but the evidence is in favour of the two diseases being separate entities. There may as yet be no specific treatment for this syndrome, but much can be done to help these children. Drugs may be needed to control epilepsy, and when dystonia is severe it may be possible to alleviate this by medical or surgical means. Also there will be other problems needing expert management, such as the provision of alternative means of communication if dysarthria is marked. The hope for the future is that now the cause has been found it will be possible to use methods such as antioxidative therapy and gene induction procedures.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Basal Ganglia / pathology
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 20
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Mutation / genetics*
  • Neurologic Examination
  • Pantothenate Kinase-Associated Neurodegeneration / diagnosis*
  • Pantothenate Kinase-Associated Neurodegeneration / genetics
  • Pantothenate Kinase-Associated Neurodegeneration / therapy
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*

Substances

  • Phosphotransferases (Alcohol Group Acceptor)
  • pantothenate kinase