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|LETTER TO EDITOR
|Year : 2021 | Volume
| Issue : 6 | Page : 1848-1849
Nemaline Rods in a Patient of Chorea-Acanthocytosis with a Novel Pathogenic Mutation of VPS13A Gene
Qian Zheng1, Lina Zhu1, Chunlin Zhang2, Ling Jiao1
1 Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China
2 Department of Biology, College of Basic Medical, Guizhou Medical University, Guiyang, Guizhou Province, China
|Date of Web Publication||23-Dec-2021|
Dr. Chunlin Zhang
College of Basic Medical, Guizhou Medical University, Guiyang - 550 004, Guizhou, Province
Dr. Ling Jiao
Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guiyang - 550 004, Guizhou Province
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Zheng Q, Zhu L, Zhang C, Jiao L. Nemaline Rods in a Patient of Chorea-Acanthocytosis with a Novel Pathogenic Mutation of VPS13A Gene. Neurol India 2021;69:1848-9
A 31-year-old male, who was born to consanguineous parents but did not have a family history of neurological disease, was admitted to our neurology department after he complained of involuntary movements of the face, neck, and upper extremities for seven years. At the age of 24 years, he began experiencing abnormal, repetitive, involuntary, and nonpurposeful blinking, tooth baring, pouting, grimacing, involuntary neck turning, shrugging, and limb writhing. In the following years, his choreoathetosis progressively worsened, and he developed slight dysarthria.
Physical examination revealed that chorea manifested as repetitive, involuntary, and nonpurposeful movements of the face, neck, and upper limbs. Orofacial and lingual dyskinesia occurred. He walked with a bizarre gait. Deep tendon reflexes were diminished. He failed to complete heel-knee-tibia and finger-nose tests. He was a short man, with amyotrophic bilateral zygomaticus and alveololabialis. Other systemic examination was normal.
Laboratory investigations revealed that creatine kinase (CK) and lactic acid levels increased to 4487.85 U/L (normal = 38.00 U/L to 174 U/L) and 5.68 mmol/L (normal = 0.60 to 2.20 mmol/l), respectively. Nerve conduction analysis revealed motor axonal neuropathy. Brain magnetic resonance imaging showed that the structure and signal of the brain parenchyma were normal. Other routine investigations were normal.
A biopsy of the left biceps brachii was performed on the basis of the increased level of CK. H and E staining occasionally revealed small angular and regenerating fibers [Figure 1]a. Modified Gomori trichrome-stained cryostat sections displayed a moderate number of the collections of the rod structures preferentially located under the sarcolemma [Figure 1]b. Immunohistochemistry frequently revealed fibers with internal nuclei [Figure 1]c. We further performed an electron microscopy of peripheral blood and found an increased number of acanthocytes [Figure 2]. Sequence analysis of the exome revealed exhibited VPS13A:c.444delA, which was a homozygote mutation of a 38-exon gene on chromosome 9, thereby causing changes in p.D148Tfs*2 [Figure 3]. The variation did not belong to the polymorphic loci, and the incidence in the population was extremely low. This mutation has not been reported in the Human Gene Mutation Database. Therefore, the patient was eventually diagnosed with chorea-acanthocytosis (ChAc).
|Figure 1: Muscle biopsy specimen obtained from the left biceps brachii (a) H and E staining demonstrated multiangular and regenerating fibers (black arrow). Original magnification: 200×. (b) Modified Gomori trichrome staining of the transverse section of the biopsied muscle demonstrated revealed nemaline rods clustering preferentially in a subsarcolemmal location (red arrows). Original magnification: 400×. (c) Immunohistochemistry demonstrated fibers with few internal nuclei (blue arrows). Original magnification: 500×|
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|Figure 2: Electron microscopy of peripheral blood with an increased number of acanthocytes. Original magnification: 400×|
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|Figure 3: Sequencing analysis of VPS13A of this patient and his parents. VPS13A sequencing in our patient revealed a homozygous deletion in exon 38 (c.4441delA), leading to a premature translation termination (p.D1483Tfs*2). VPS13A sequencing in his parents displayed a heterozygous mutation of the same genetic mutation|
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ChAc is present with involuntary movements, psychiatric symptoms, amyotrophy, and erythrocyte acanthocytosis. Clinical neuromuscular symptoms, such as muscle weakness/atrophy, reduced or absent deep tendon reflexes, and hypotonia, are common hallmarks of ChAc. Our patient exhibited marked progressive involuntary movements, psychiatric symptoms, and erythrocyte acanthocytosis. A diagnosis of ChAc was confirmed via genetic testing although no positive family history was reported.
ChAc is an autosomal recessive inherited movement disorder associated with mutations in VPS13A on chromosome 9q21. VPS13A sequencing in our patient exhibited a homozygous deletion in exon 38 (c.4441delA), thereby leading to premature translation termination (p.D1483Tfs*2). VPS13A sequencing in his parents revealed a heterozygous mutation of the same genetic mutation. This genetic mutation of VPS13A is new in the Human Gene Mutation Database.
Nemaline rods may form under various pathological conditions, and the precise mechanisms of rod formation remain unclear. This formation is the hallmark of congenital or adult-onset nemaline myopathy. However, nemaline rods have also been found in many conditions, such as mitochondrial diseases, tenotomized muscles, end-plate myopathy induced by prostigmine, normal adult myotendinous junction, and various other myopathies., They have also been found at the center of target structures associated with acute denervation. In 2005, the first study described a patient who suffered from ChAc and exhibited nemaline rods distributed in biopsied muscles. Nemaline rods were also found under the sarcolemma of our patient, which is the second case of ChAc with nemaline rods. Nemaline rods are not pathognomonic for ChAc, but muscle membranous structures have been suggested to be disordered. Histopathological findings of myogenic changes and increased serum CK levels of our patient indicated that nemaline rods might be a consequence of the underlying myopathic condition in ChAc.
In conclusion, this is the first report of a new p.D1483Tfs*2 VPS13A mutation at the homozygous state, which expands the VPS13A gene mutation spectrum. And nemaline rods can be found under the sarcolemma in patient of ChAc.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
This study was supported by the Natural Science Foundation of the Scientific and Technologic Bureau of Guiyang, Guizhou, China ((2017)30-30), the Natural Science Foundation of Guizhou Province of China (LH(2015)7414), and the Department of Science and Technology of Guizhou Province ((2017)5718).
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]