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|LETTER TO EDITOR
|Year : 2013 | Volume
| Issue : 2 | Page : 169-170
Mineral deposition on magnetic resonance imaging in chorea-acanthocytosis: A pathogenic link with pantothenate kinase-associated neurodegeneration?
Bhavna Kaul1, Vinay Goyal1, Garima Shukla1, Achal Srivastava1, Ajay Garg2, Benedikt Bader3, Adrian Danek3, Susan Hayflick4, Madhuri Behari1
1 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Neuroradiology, All India Institute of Medical Sciences, New Delhi, India
3 Neurology Clinic and Polyclinic, Ludwig-Maximilians-University, Munich, Germany
4 Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, USA
|Date of Submission||05-Dec-2012|
|Date of Decision||03-Jan-2013|
|Date of Acceptance||10-Mar-2013|
|Date of Web Publication||29-Apr-2013|
Department of Neurology, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kaul B, Goyal V, Shukla G, Srivastava A, Garg A, Bader B, Danek A, Hayflick S, Behari M. Mineral deposition on magnetic resonance imaging in chorea-acanthocytosis: A pathogenic link with pantothenate kinase-associated neurodegeneration?. Neurol India 2013;61:169-70
|How to cite this URL:|
Kaul B, Goyal V, Shukla G, Srivastava A, Garg A, Bader B, Danek A, Hayflick S, Behari M. Mineral deposition on magnetic resonance imaging in chorea-acanthocytosis: A pathogenic link with pantothenate kinase-associated neurodegeneration?. Neurol India [serial online] 2013 [cited 2020 Sep 23];61:169-70. Available from: http://www.neurologyindia.com/text.asp?2013/61/2/169/111129
A 33-year-old lady presented with a history of generalized tonic-clonic seizures of 5 years duration and involuntary chewing and lip biting since 2 months. Abnormal involuntary orofacial movement included chewing, tongue protrusion, and spitting. She reported ideas of self-hatred and self mutilation in the form of deliberate lip biting. Examination revealed orofacial dyskinesias consisting of repetitive chewing and lip pursing and motor tics in the form of tongue clicking and hiccoughs. Oral mucosa and tongue revealed multiple ulcerations. Motor system examination showed generalized hyporeflexia with distal wasting. Serum creatine kinase was elevated (1,038 IU/L), fresh blood smear showed peripheral acanthocytosis up to 10%. Head computed tomography (CT) scan showed bilateral caudate atrophy [Figure 1]a. Magnetic resonance imaging (MRI) brain showed bilaterally symmetrical hypo-intensities in globus pallidus, substantia nigra, and red nucleus on T2- and susceptibility-weighted images along with caudate and posterior putaminal atrophy [Figure 1]b-d. These features were suggestive of mineral (iron or another paramagnetic substance) deposition, thus mimicking the "eye-of-the-tiger" sign as described in pantothenate kinase-associated neurodegeneration (PKAN). The Western blot showed absence of chorein in erythrocyte membranes confirming the diagnosis of chorea-acanthocytosis (ChAc).
|Figure 1: Head CT scan and MRI of the brain: (a) CT scan showing bilateral caudate atrophy; (b) T1 - weighted axial images showing bilateral iso- to hypointense signal alterations in the internal globus pallidus and posterior putaminal atrophy; (c) T2 - weighted axial images showing hypointense signal in the same are suggestive of mineral deposition; (d) susceptibility - weighted images (axial view) confirming mineral depositions corresponding to hypointense signal in the above areas|
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The molecular defect in ChAc is caused by mutations of VPS13A on chromosome 9q12 leading to absence or marked reduction of chorein, a membrane protein of yet unknown function.  In PKAN, mutations of PANK2 occur on chromosome 20p13 coding for pantothenate kinase 2.  PANK2 mutations are believed to cause oxidative stress due to mitochondrial coenzyme A (CoA) deficiency. As a substrate in CoA biosynthesis, cysteine may accumulate in cells and undergo rapid auto-oxidation in the presence of free iron, generating free radicals.  Both disorders are part of the 'core' neuroacanthocytosis syndromes, clinically characterized by chorea, dystonia, and less frequently, Parkinsonism More Details.
MRI of the brain in PKAN shows the classic 'eye-of-the-tiger' appearance, attributed to iron deposition in the globus pallidus, which causes a proton relaxation effect, resulting in a decrease in T1 and T2 relaxation times and decreased signal intensity in the globus pallidus, while the central hyper-intensity is attributed to intense gliosis. Pooled data of three large series showed that 94% of patients with this sign on MRI had PANK2 mutation.  Typical MRI findings in ChAc include striatal atrophy (involving the caudate more than the pallidum) and putaminal atrophy.  To our knowledge, this is the first report of mineral deposition in a confirmed case of ChAc and the first confirmed case of chorea-acanthocytosis from India. Recently, Lee et al., reported a paramagnetic substance in susceptibility-weighted MRI in a case clinically assumed to represent ChAc.  Another report by Gautam et al., described radiological findings akin to the 'eye-of-the-tiger' sign in a patient presenting with tremors, rigidity, chorea, and one episode of seizure along with peripheral acanthocytosis. Genetic testing was not done for PKAN or for ChAc in this patient.  The MRI finding of mineral deposition in our patient raises the question of whether these two phenotypically related but genetically distinct disorders do indeed have a common pathogenic basis. We hypothesize that mutations in VPS13 could lead to enzymatic defects resulting in brain mineral accumulation in these patients, which may prove to be the final common pathway responsible for clinical manifestations in both these neuroacanthocytosis syndromes. Although a plain CT is sufficient to document caudate atrophy, we suggest that susceptibility-weighted MRI should be done to systematically document mineral deposition in all patients of ChAc to shed light on pathogenesis of this rare disorder. We also recommend that all patients of suspected PKAN with atypical features who have evidence of pallidal mineral deposition on neuroimaging but test negative for PANK2 mutation should be screened for the deficiency of chorein protein in erythrocytes.
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