Pattern of disease progression in atypical form of pantothenate-kinase-associated neurodegeneration (PKAN) - Prospective study.
BACKGROUND
Classic form of pantothenate-kinase-associated neurodegeneration (PKAN), caused by mutation in PANK2 gene, is characterized by early onset, severe neurological impairment and rapid disease progression. In less precisely described form of atypical PKAN, clinical course is associated with late onset, less severe motor impairment and slower disease evolution. The aim of this study was to assess a pattern of disease progression in atypical PKAN, by following development of specific milestones.


METHODS
The clinical characteristics and the disease course of 9 genetically confirmed patients with atypical form of PKAN were evaluated. Time latencies from the disease onset to the appearance of specific clinical milestones were estimated in order to assess the disease progression.


RESULTS
Most frequent disease presentation in our patients was characterized with early and prominent oromandibular dystonia (OMD), followed by severe generalized dystonia and early loss of mobility within the first five years of prolonged disease duration (18.7 ± 10.0 years). Eight out of 9 patients reached 7 significant clinical milestones (OMD, generalized dystonia, dysarthria, dysphagia, postural instability, gait difficulties, ADL dependency) in the first 4.6 years of disease course. Afterwards, a long-lasting, relatively stable period of slower progression was complicated predominantly with skeletal deformities (developed after 7.0 ± 2.8 years).


CONCLUSIONS
Majority of milestones which might significantly influence functional abilities and quality of life in patients with atypical form of PKAN developed in the course of the first five years of the disease, followed by a long-lasting, relatively stable period of slower progression.
Institute of Neurology, Clinical Center of Serbia, Belgrade, Serbia.
Aleksandra
A
Tomić
Institute of Neurology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Igor
I
Petrović
Institute of Neurology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Marina
M
Svetel
Institute of Neurology, Clinical Center of Serbia, Belgrade, Serbia.
Valerija
V
Dobričić
Institute of Neurology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Nataša
N
Dragašević Mišković
Institute of Neurology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address: vladimir.s.kostic@gmail.com.
Vladimir S
VS
Kostić
D000328:Adult; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D006211:Pantothenate Kinase-Associated Neurodegeneration / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D011446:Prospective Studies; D012189:Retrospective Studies; D055815:Young Adult
Clinical milestones; Disease progression; Dystonia; PKAN