a 40-year - old man presented with involuntary movement of his right hand and left foot .
the symptom started when he was approximately 35 years of age and had slowly worsened .
his disability progressed over the following years and was restricted to his right hand and left foot .
he had no significant medical history and no history of exposure to neuroleptic drugs , hypoxic environments , or toxic metabolites , except for the intermittent inhalation of silica dust at his workplace .
there was no family history of neurological disorders . on examination , the patient had dystonic posture of his right hand , which caused alternating dorsiflexion and neutralization with supination of the forearm and flexion of the metacarpophalangeal joint .
an ophthalmologic evaluation showed no kayser - fleischer rings , optic atrophy , or pigmentary retinopathy .
serum ferritin and copper levels were normal , and a blood smear was negative for acanthocytes .
the results of other laboratory tests , including serum electrolytes , erythrocyte sedimentation rate , thyroid function test , liver function test , autoimmune antibodies , ferritin , copper , ceruloplasmin , and a blood smear were normal , except for borderline - low 24-hour urine copper ( 10.2 g / dl , normal 1530 g / dl ) .
a t1-weighted brain mri study showed hyperintensity bilateral anteromedial globus pallidi ( figure 1a ) .
a t2-weighted mri showed hypointensity in the bilateral globus pallidi with hyperintense core , the typical  eye - of - the - tiger  sign ( figure 1b ) .
genomic dna was extracted from peripheral blood , and polymerase chain reactions ( pcr ) were preformed . the dyt1 gag deletion ( dele302/303 )
automated dna sequence analyses revealed two single - base variants in exon 3 and exon 4 .
both pathological variants result in changes to conserved amino acids in the pank2 protein : asp268 gly ( p.d268 g ) and arg330prp ( p.r330p ) . to our knowledge , this is the first patient identified with the mutation p. r330p and the second patient with the mutation p.d268 g .
the dystonia of the patient s right hand and left foot did not respond to levodopa / carbidopa ( 100/25 mg t.i.d ) .
treatment with diazepam ( 5 mg t.i.d ) and trihexyphenidyl ( 2 mg t.i.d ) slightly improved the dystonia .
however , his dystonia worsened after one year , and he could not walk without a cane .
our patient had an atypical phenotype of the pank2 gene : compound heterozygous mutations in exon 3 ( p.d268 g ) and exon 4 ( p.r330p ) . to our knowledge
, our patient is the first to be identified with mutation p.r330p and the second to be identified with mutation p.d268 g .
the onset of atypical pkan is known to be 1st three decades ( mean age 13.6).2 in a previous study , 23 patients with atypical pkan were analyzed , and the mean age at onset was 13.7 years ( range 128 years ) .
patients with atypical pkan had variable clinical features , including parkinsonism , corticospinal tract involvement , speech disturbances such as palilalia , and psychiatric symptoms.3 our patient presented with dystonia and gait disturbance , which are the predominant symptoms of classical pkan . the implication of the  eye - of - the - tiger  sign on a brain mri is controversial.3,4 the  eye - of - the - tiger
 sign on mri is not pathognomic of pkan , and some patients with pank2 mutations do not have this sign and sometimes , it may appear only transiently .
this sign has also been reported in corticobasal degeneration , progressive supranuclear palsy , anoxicischemic leukoencephalopathy , and early - onset levodopa - responsive parkinsonism.4 however , a previous study reported that all patients clinically suspected of nbia with the  eye - of - tigersign  have mutations in pank2 and that all patients without the typical mri finding do not have these mutations.3 in our patient , the mri finding and presenting symptoms were consistent with classic pkan , while the age at onset and the absence of other features such as retinal degeneration , optic atrophy , and delayed development were consistent with atypical disease or other subtypes of nbia .
genetic studies identified compound heterozygous missense mutations ( p.d268 g , p.r330p ) in exons 3 and 4 of pank2 . to our knowledge , this is the first description of the p.r330p mutation .
the mutation p.d268 g was reported previously in a chinese patient with heterozygous missense mutations ( p.
d268 g , p.i391n).5 others have attempted to establish a correlation between the genotype and phenotype .
although the linkage between mutations and residual enzymatic activities related to the age of onset has been partially demonstrated , the phenotype is still difficult to predict based on the presence of pank2 mutations.3,68 there were no overlapping clinical features between our patient and the chinese patient with the p.d268 g mutation , except for the typical mri finding .
the chinese patient s disease began at 17 years of age , and his predominant symptoms were tremor and rigidity . it is presumed that modifier effects of allelic genes and environmental factors played a roll in the phenotypic differences between these two patients.3 the pank2 gene codes for pantothenate kinase , which is an essential regulatory enzyme in coenzyme a ( coa ) biosynthesis , catalyzing the cytosolic phosphorylation of pantothenate ( vitamin b5 ) the enzyme of the initial and rate - limiting step in coa biosynthesis : the phosphorylation of pantothenate , n - pantothenoyl - cysteine and pantetheine.9 to compensate for the partial enzymatic deficiency in patients with pkan , supplement of pantothenate ( vitamin b5 ) have been tried without conclusive benefit.3 previous case reports using pallidal deep - brain stimulation reported improvement of dystonia in patients with pkan , but it was also restrictive effect.10 further study is needed for early diagnosis of pkan , correct prediction of disease progress , and rational treatment .
 pantothenate kinase - associated neurodegeneration ( pkan ) is an autosomal recessive disorder that is characterized by mutations in the pantothenate kinase 2 gene ( pank2 ) and typical magnetic resonance imaging findings . 
 we report a case of atypical pkan presenting with generalized dystonia . our patient had compound heterozygous mutations in the pank2 gene , including mutation in exon 3 ( p.d268 g ) and exon 4 ( p.r330p ) . to our knowledge 
 , this patient is the first to have the p.r330p mutation and the second to have the p.d268 g mutation . 