Pantothenate Kinase-associated Neurodegeneration - History & Epidemiology

History & Epidemiology

PKAN was first described by Hallervorden and Spatz (1922). Their discovery was brought about by a diagnosis of a family of 12 in which five sisters exhibited progressively increasing dementia and dysarthria. Autopsies revealed brown discolorations in different areas of the brain (particularly of interest were the globus pallidus and substantia nigra regions). Further investigation and description was brought about by Meyer (1958) who diagnosed 30 separate cases of PKAN. Meyer(1958) was followed by Elejalde et al. (1978) who described 5 affected family members and hypothesized that the disorder originated in central Europe, backing up his hypothesis with clinical and genetic analysis. Further investigation and insights were provided by Malmstrom-Groth and Kristensson (1982) and Jankovic et al. (1985).

Diagnosis of PKAN hit a milestone with the availability of MRIs, as well as the in-depth descriptions of those MRIs provided by Littrup and Gebarski (1985), Tanfani et al. (1987), Sethi et al. (1988),Angelini et al. (1992), Casteels et al. (1994), and Malandrini et al. (1995). The gene was localized to chromosome 20p by Taylor et al. (1996) who suggested that this disorder should be referred to as neurodegeneration with brain iron accumulation (NBIA1) to avoid the objectionable eponym of Hallervorden-Spatz. The disease was named 'pantothenate kinase-associated neurodegeneration' or PKAN by Zhou et al. (2001) who suggested the name to avoid misinterpretation and to better reflect the true nature of the disorder. Most recently Pellecchia et al. (2005) published a report of 16 patients afflicted with PKAN, confirmed by genetic analysis.

Survival rates for those diagnosed with typical PKAN is 11.18 years with a standard deviation of 7.8 years. Prevalence data regarding this disorder remains incomplete, however it is estimated that anywhere between 1 in 1,000,000 to 3 in 1,000,000 individuals will be afflicted with this disorder (based upon observed cases in a population), but once again this is only an estimate as the disease is so rare it is difficult to statistically and accurately ascertain.