|Year : 2019 | Volume
| Issue : 3 | Page : 130-133
Dystonic opisthotonus: A rare phenotype of adrenoleukodystrophy
Sindhu D Mallikarjuna1, Sadanandavalli R Chandra1, Hansashree Padmanabha1, Rita Christopher2
1 Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
2 Department of Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
|Date of Submission||03-Jun-2019|
|Date of Decision||06-Aug-2019|
|Date of Acceptance||12-Sep-2019|
|Date of Web Publication||04-Dec-2019|
Dr. Sadanandavalli R Chandra
Faculty Block, Department of Neurology, Neurocentre, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru 560029, Karnataka.
Source of Support: None, Conflict of Interest: None
X-linked adrenoleukodystrophy (X-ALD) is a pan-ethnic disorder and affects approximately 1:20,000 males (Moser HW, Mahmood A, Raymond GV. X-linked adrenoleukodystrophy. Nat Rev Clin Pract Neurol 2007;3:140-51; Natarajan A, Christopher R, Netravathi M, Bhat M, Chandra SR. Liquid chromatography-tandem mass spectrometry method for estimation of a panel of lysophosphatidylcholines in dried blood spots for screening of X-linked adrenoleukodystrophy. Clin Chim Acta 2018;485:305-10). Phenotypes include the childhood cerebral form, which affects children who present with rapid cognitive decline. Adolescents and adults present with spastic paraparesis or adrenomyeloneuropathies and also as pure Addison's disease. The less common presentations are psychosis and cortical blindness. A 9-year-old boy presented with progressive cognitive decline, behavioral disturbance, extrapyramidal symptoms, and opisthotonic posturing. Magnetic resonance imaging of brain and blood levels of very long-chain fatty acids lysophosphatidylcholine confirmed X-ALD.
Keywords: Dystonia, opisthotonus, very long-chain fatty acids lysophosphatidylcholine, X-linked adrenoleukodystrophy
|How to cite this article:|
Mallikarjuna SD, Chandra SR, Padmanabha H, Christopher R. Dystonic opisthotonus: A rare phenotype of adrenoleukodystrophy. Ann Mov Disord 2019;2:130-3
|How to cite this URL:|
Mallikarjuna SD, Chandra SR, Padmanabha H, Christopher R. Dystonic opisthotonus: A rare phenotype of adrenoleukodystrophy. Ann Mov Disord [serial online] 2019 [cited 2020 Apr 9];2:130-3. Available from: http://www.aomd.in/text.asp?2019/2/3/130/272280
| Key message:|| |
ALD spectrum is expanding and a high degree of suspicion is needed as treatment options are available if diagnosed early.
| Introduction|| |
X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder, which occurs due to mutations in the ABCD1 gene located on chromosome Xq28., This gene codes for the peroxisomal binding cassette (ABC) protein belonging to subfamily D transporter protein known as adrenoleukodystrophy protein. A defect in this gene results in defective transport of very long-chain fatty acids (VLCFA) into the peroxisome for degradation by beta-oxidation., This results in the accumulation of VLCFA in various tissues such as white matter of brain, peripheral nerves, fibroblasts, blood, adrenal glands, and testis. The clinical spectrum of this disorder is wide, ranging from asymptomatic patients, subclinical adrenal insufficiency to severe forms such as childhood cerebral ALD, and adrenomyeloneuropathies, which becomes symptomatic by third to fourth decade. In various reports, 20%–30% of female carriers are said to become symptomatic by sixth decade. Ten percent of patients may even present as pure Addison's disease. The usual patients present with behavioral disturbances, visual symptoms, spastic paraparesis, cognitive decline, ataxia, apraxia, seizures, and become bed bound by three to four years. Extrapyramidal involvement is a very rare manifestation of X-ALD, and it is reported in very few cases.,
Laboratory markers are excess of VLCFA, which includes absolute levels of hexacosanoic acid (C26), the ratio of C26 to tetracosanoic acid (C26:C24), and the ratio of C26 to docosanoic acid (C26:C22) in plasma red cells, white cells, and cultured fibroblasts. In addition, low serum sodium and chloride and elevated potassium are observed. Low serum cortisol and poor response of 17 hydroxyl ketosteroids after adreno cortico trophic hormone stimulation are noticed. Mild elevation of cerebrospinalfluid protein may occur.
Dystonia is a syndrome of sustained muscle contractions, which results in twisting, patterned, or repetitive movements and postures. This is due to pathological motor programming, resulting from mismatch between sensory input and motor output, and therefore considered a network disorder. Other pathomechanisms postulated are maladaptive cortical plasticity, disorganization in primary somatosensory cortex, impaired central inhibition of surrounding muscles, and defective temporal discrimination in the limbs. There is a hypothesis of striosomes and matrix forming a three-component neurochemical model of basal ganglia circuits, resulting in altered push-pull function of the direct excitatory and indirect inhibitory pathways. However, the exact pathomechanisms remain unclear.
| Case Report|| |
A 9-year-old boy, only child born to non-consanguineous parents with normal birth and developmental history, presented with behavioral changes in the form of inattention, restlessness, and aggressive behavior of 1.5-year duration. This was followed by tics in the form of winking his left eye, which he could voluntarily suppress, visual agnosia as evidenced by searching for objects in front of him even though he was not hitting against walls or doors, progressive cognitive decline, cerebellar involvement in the form of gait ataxia, difficulty in carrying food to the mouth, and dysarthria. Few months later, he developed dystonic posturing of both ankles. Over a year later, his symptoms worsened and he had intermittent twisting movements of upper limbs and opisthotonic posturing of trunk [Figure 1]. He had nystagmus, flexion at right elbow, extension of left elbow and fisting of both hands, bow-like trunk, extended legs, and plantar flexed ankles. Ophthalmic examination showed no kayser fleisher ring and fundus showed bilateral primary optic atrophy. His diagnostic workup included estimation of amino acids and acylcarnitines by tandem mass spectrometry, which was noncontributory. Serum creatinine kinase was elevated (558 IU/L) due to persistent posturing. Brain magnetic resonance imaging revealed T2 and fluid attenuated inversion recovery images hyperintensities involving both parietal and occipital white matter, extending into the posterior limb of the internal capsule, left cerebellum, middle cerebellar peduncle, and corticospinal tract in pons and medulla [Figure 2]. Blood VLCFA lysophosphatidylcholines (LPCs), the diagnostic markers for X-ALD, estimated by liquid chromatography–tandem mass spectrometry method showed significantly elevated C26:0-LPC (0.67 µmol/L as against <0.1 µmol/L, which is normal). Blood C24:0-LPC level was also elevated (0.51 µmol/L as against the normal value of <0.25 µmol/L). His serum sodium was 140 mEq/L, potassium was 4.48 mEq/L, and chloride was 104.9 mE/L. Ultrasound abdomen was noncontributory. Child was managed with muscle relaxants, trihexyphenidate, clonazepam, and steroids. At the time of discharge, there was symptomatic improvement in the form of reduced opisthotonus and ability to turn in bed.
|Figure 1: Child showing opisthotonus and flexion at the right elbow, bilateral wrist flexion, extension of legs, and plantar flexed ankle|
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|Figure 2: T2 images show white matter hyperintensities involving both parieto-occipital regions, splenium, brain stem up to medulla, and cerebellum|
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| Discussion|| |
Movement disorders are very uncommon in leukodystrophies as most often they cannot be clinically expressed due to spasticity even when present. Ataxia is reported with metachromatic leukodystrophy, Alexander disease, hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome), ALD, and childhood ataxia with vanishing white matter. Dystonia is reported with MCT8-specific thyroid hormone cell transporter deficiency, Parkinsonism More Details with hereditary diffuse leukoencephalopathy with spheroids, and chorea in Gordon Holmes syndrome as well as palatal myoclonus in Alexander disease. However, movement disorders can be seen in other types of leukoencephalopathies.
Marsden et al. reported patients with ALD presenting as familial spinocerebellar syndrome, and Ohno reported features of olivopontocerebellar atrophy., Patients have been reported with bronzing of the skin as early as four years with quadriparesis, pseudobulbar features, and decerebrate posturing. Less common presentations are repeated vomiting, personality change, inappropriate laughter, and acute adrenal crisis. Pathologically, there is severe destruction of myelin asymmetrically in various parts of cerebral hemispheres; brain stem, spinal cord and optic nerves, and sudanophil-positive macrophages were seen in these lesions. There is an autosomal-recessive neonatal form, which presents as hypotonia, seizures, severe psychomotor retardation, blindness due to optic atrophy, and adrenal atrophy without obvious hypoadrenalism.
Dystonic opisthotonus is due to failure of reciprocal inhibition at spinal cord between agonist and antagonists. Opisthotonus seen in our patient could be due to altered cortical regulatory mechanisms, which involve caudal supplementary motor area, bilateral sensory motor cortex, posterior cingulate, and mesial parietal cortex in the form of reduced function of the cortical inhibitory circuits, which alter the spinal mechanisms. Our patient showed the radiological extension of pathology to parietal regions and brain stem as well. This case is reported for its phenotypic rarity and to sensitize professionals for this possibility.
Treatment consists of adrenal replacement therapy and diet enriched with monounsaturated fatty acids. Avoiding long-chain fatty acids is useful when used early in addition to symptomatic treatment of presenting features. Genetically matched stem cell transplantation is the only effective treatment option in asymptomatic patients. Gene therapy using patients' own stem cells modified by noninfective virus, which will introduce the ABCD1 gene is being tried. Bone marrow transplantation when carried out early slows down the progression.
National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India.
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
The diagnosis of this patient for very long-chain fatty acid levels was supported by funds from the Department of Biotechnology, Ministry of Science and Technology, New Delhi, Government of India (Grant No. BT/PR26150/MED/12/768/2017).
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]