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Table of Contents    
Year : 2013  |  Volume : 61  |  Issue : 2  |  Page : 175-176

A novel PANK2 mutation in a 12-year-old Chinese boy with pantothenate kinase-associated neurodegeneration

Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China

Date of Submission11-Jan-2013
Date of Decision18-Feb-2013
Date of Acceptance09-Mar-2013
Date of Web Publication29-Apr-2013

Correspondence Address:
Yan-Ming Xu
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province
People's Republic of China
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.111134

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How to cite this article:
Pan LS, Yu LH, Yin YY, Xu YM. A novel PANK2 mutation in a 12-year-old Chinese boy with pantothenate kinase-associated neurodegeneration. Neurol India 2013;61:175-6

How to cite this URL:
Pan LS, Yu LH, Yin YY, Xu YM. A novel PANK2 mutation in a 12-year-old Chinese boy with pantothenate kinase-associated neurodegeneration. Neurol India [serial online] 2013 [cited 2020 Nov 29];61:175-6. Available from:


A 12-year-old boy, born to healthy non-consanguineous Chinese parents, presented with abrupt onset limb dystonia. Pregnancy and delivery had been unremarkable. There was no family history of any neurological disease. His academic performance was average to above-average. Development had been normal until the age of 11.5 years, when the patient began to present with varus and external rotation of the left foot due to dystonia while walking. The walking-associated dystonia extended rapidly to the right lower limb and both upper limbs within 4 months. Due to bilateral lower limb dystonia, the boy presented with a gait abnormality manifested by varus and external rotation affecting both feet, accompanied by an abnormal posture involving frequent involuntary rotation of the left upper extremity toward the tergum, as well as involuntary flexion of the right wrist during walking. Strikingly, all the abnormalities disappeared during rest. Symptoms aggravated rapidly and no response to treatment with levodopa, benserazide tablets (187.5 mg/day), and clonazepam (2 mg/day) given for one month was observed. Neurological examinations showed no abnormality during rest but severe limb dystonia affecting all extremities during walking, which visibly disturbed the gait. During walking, both feet manifested varus and external rotation, accompanied by involuntary movements affecting both upper extremities. The left upper extremity frequently rotated toward the tergum, and the right upper extremity presented with wrist flexion. Neither eye showed pigmentary retinopathy or optic atrophy. Other neurological, cognitive, and laboratory and general tests revealed no abnormalities. T 2 -weighted brain magnetic resonance imaging (MRI) showed a typical eye-of-the-tiger sign [Figure 1].
Figure 1: T2-weighted brain MRI showing the typical eye-of-the-tiger sign (arrows)

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The child was genotyped in the Pantothenate kinase 2 (PANK2) gene using a protocol approved by Sichuan University. Genetic studies, as described previously, [1] detected two heterozygous PANK2 mutations [Figure 2]. A c. 1555T > C mutation was detected, and it corresponds to a transition from phenylalanine to leucine at codon 519 (p. F519L, GenBank accession NP_705902.2). To our knowledge, this F519L mutation has not been reported in the literature. The other mutation, c. 1607A > G (p. Y536C), has previously been described. [2] Neither mutation was found in the 500 normal Chinese healthy controls.
Figure 2: Two heterozygous mutations in the PANK2 gene of the present patient: A novel mutation c. 1555T > C (p. F519L), and a previously described mutation c. 1607A > G (p. Y536C)

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PANK2 contains an N-terminal sequence of 29 residues that is predicted to target the protein to mitochondria. [3] Residues 211-570 of mammalian PanKs contain the catalytic core, and the highly conserved segment VVFVGNFLR 517-525 is essential for PANK2 activity. [4] Both the F519L and Y536C mutations detected in this case lie within the region spanning residues 211 to 570, so it is likely that they reduce catalytic function without altering the subcellular localization of PANK2. In particular, the F519L mutation is likely to inhibit PANK2 activity because even conservative substitutions within the VVFVGNFLR 517-525 motif significantly reduce or even completely eliminate catalytic activity.

Numerous cases of Pantothenate kinase-associated neurodegeneration (PKAN) associated with PANK2 mutations have been reported around the world. In mainland China, however, only four cases of genetically confirmed PKAN, have been reported, and most patients showing PKAN symptoms are diagnosed according to older, more restrictive criteria based on phenotype and brain imaging, without genotyping. [5] In addition, clinicians in mainland China and other developing countries such as India, [6] continue to employ imprecise terminology, such as " Hallervorden-Spatz disease More Details." Without precise genotyping and extensive analysis, our patient, like other Chinese cases, [3],[7] might not have been correctly diagnosed with PKAN, since he did not meet the older diagnostic criteria in widespread use in China. Genetic analysis revealed that he harbors two PANK2 mutations linked to PKAN. Therefore, we recommend genetic analysis for all patients that present with both a PKAN phenotype and the eye-of-the-tiger sign in brain MRI, the presence of which correlates strongly with PANK2 mutations. [8]

  Acknowledgments Top

This study was supported by the Sichuan Key Project of Science and Technology (no. 2010SZ0086). We thank all the subjects who participated in this study.

  References Top

1.Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ. A novel pantothenate kinase gene PANK2 is defective in Hallervorden-Spatz syndrome. Nat Genet 2001;284:345-9.  Back to cited text no. 1
2.Lim BC, Ki CS, Cho A, Hwang H, Kim KJ, Hwang YS, et al. Pantothenate kinase-associated neurodegeneration in Korea: Recurrent R440P mutation in PANK2 and outcome of deep brain stimulation. Eur J Neurol 2012;194:556-61.  Back to cited text no. 2
3.Zhang YH, Tang BS, Zhao AL, Xia K, Long ZG, Guo JF, et al. Novel compound heterozygous mutations in the PANK2 gene in a Chinese patient with atypical pantothenate kinase-associated neurodegeneration. Mov Disord 2005;207:819-21.  Back to cited text no. 3
4.Zhang YM, Rock CO, Jackowski S. Biochemical properties of human pantothenate kinase 2 isoforms and mutations linked to pantothenate kinase-associated neurodegeneration. J Biol Chem 2006;2811:107-14.  Back to cited text no. 4
5.Swaiman KF. Hallervorden-Spatz syndrome. Pediatr Neurol 2001;252:102-8.  Back to cited text no. 5
6.Sachin S, Goyal V, Singh S, Shukla G, Sharma MC, Gaikwed S, et al. Clinical spectrum of Hallervorden-Spatz syndrome in India. J Clin Neurosci 2009;162:253-8.  Back to cited text no. 6
7.Song XW, Wang YL, Shi YW, Deng WY, Chen SQ, Lin H, et al. Clinical manifestations and detection of pantothenate kinase 2 gene mutation in a patient with Hallervorden-Spatz syndrome. Natl Med J China 2009;8947:3320-3.  Back to cited text no. 7
8.Hayflick SJ, Westaway SK, Levinson B, Zhou B, Johnson MA, Ching KH, et al. Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N Engl J Med 2003;3481:33-40.  Back to cited text no. 8


  [Figure 1], [Figure 2]

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