Pantothenate kinase-associated neurodegeneration initially presenting as postural tremor alone in a Japanese family with homozygous N245S substitutions in the pantothenate kinase gene.
We describe a 24-year-old Japanese woman with pantothenate kinase-associated neurodegeneration (PKAN) whose only early symptom was postural tremor in the right hand at around 18 years of age, leading to a diagnosis of essential tremor at age 21. Although she was treated with arotinolol hydrochloride and clonazepam, she gradually progressed to extrapyramidal and pyramidal signs several years later. T2-weighted magnetic resonance images (MRI) showed bilaterally marked hypointensity with a central region of hyperintensity in the globus pallidus, or the so-called "eye-of-the-tiger" sign. Six years have passed since the initial appearance of postural tremor, whereas she has not shown choreoathetosis, retinitis pigmentosa, optic atrophy, or seizure. Direct sequencing of the patient's genomic DNA revealed homozygous base substitutions in the pantothenate kinase gene (PANK2): the A764-->G substitution (N245S) due to consanguinity of her parents. Although the heterozygous form of this mutation has already been reported among several families, this is the first report of the homozygous mutation in a patient with atypical-type PKAN. This detailed description of the clinical features of a Japanese patient with PKAN arising from homozygous N245S mutations in PANK2 would be useful for elucidating the pathogenesis of PKAN.
Yamashita
Satoshi
S
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan.
Maeda
Yasushi
Y
Ohmori
Hiroyuki
H
Uchida
Yuji
Y
Hirano
Teruyuki
T
Yonemura
Kiminobu
K
Uyama
Eiichiro
E
Uchino
Makoto
M
D000050:Acanthocytes / Q000473:pathology; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D044466:Asian People; D001216:Asparagine / Q000235:genetics; D001479:Basal Ganglia / Q000473:pathology; D001931:Brain Mapping; D002998:Clonazepam / Q000627:therapeutic use; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D011412:Propanolamines / Q000627:therapeutic use; D012694:Serine / Q000235:genetics; D013194:Staining and Labeling / Q000379:methods; D014202:Tremor / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*
D000927:Anticonvulsants; D011412:Propanolamines; C024523:arotinolol; D012694:Serine; D002998:Clonazepam; D001216:Asparagine; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase