Case Report

Adrenoleukodystrophy manifesting as spinocerebellar degeneration

Sanjay Mishra, Manish Modi, Chandi P. Das, Sudesh Prabhakar Department of Neurology, PGIMER, Chandigarh - 160 012, Punjab, India

X-linked (XALD) is an inherited Parents also noticed that he became more talkative and disorder of peroxisomal metabolism. Atypical presentations argumentative. There was no history of decreased vision/hearing, have been occasionally reported in literature. However, focal weakness, decreased sensations or . His birth and extrapyramidal and cerebellar manifestations are distinctly development was normal. One of his brothers had died at the age rare. We report a patient of X-linked adrenoleukodystrophy of three years with acute gastroenteritis like illness. Examination with cranial and cervical dystonia and neurological revealed features of dysautonomia on autonomic testing presentation resembling spinocerebellar degeneration (orthostatic hypotension, inadequate heart rate variability with followed by a brief review of relevant literature. deep breathing with inadequate rise in blood pressure on cold pressor and mental arithmetic testing). MMSE score was 30/30. Key words: Adrenoleukodystrophy, extrapyramidal, Detailed higher function testing did not reveal any significant spinocerebellar degeneration. abnormality. Speech was ataxic with a spastic component. He had broken pursuits with horizontal gaze evoked . Release signs including palmomental reflex, pout and glabellar X-linked adrenoleukodystrophy (XALD) is a rare inherited tap were present. There were bilateral pyramidal (hyperreflexia . Six phenotypes of the disease have been and extensor plantars) and cerebellar signs. In addition, he had described.[1] The most rapidly progressive childhood cerebral type cervical dystonia (antecollis) and cranial dystonia (frontalis/ is the most common followed by gradually evolving orbicularis dystonia). adrenomyeloneuropathy.[1] Extrapyramidal manifestation is very Investigations revealed low serum cortisol, normal serum rarely reported in patients with XALD. We report a patient of luteinizing hormone, follicle-stimulating hormone, testosterone and adrenoleukodystrophy having dystonia and clinical presentation thyroid hormone levels. conduction study showed normal resembling spinocerebellar degeneration. latency, amplitude and conduction velocity of motor and sensory . Visual evoked potentials were normal. Brainstem auditory Case Report evoked response showed prolonged interpeak latency between I­ III and I-V waves on both the sides. Contrast enhanced computed A 29 year old male presented with history of progressive tomography (CT) of the abdomen showed atrophy of both adrenal darkening of complexion for 20 years. Four years ago, he was glands. Magnetic resonance imaging (MRI) of the brain showed investigated and was found to have low serum cortisol-2.4 µg/dl hyperintensities on T2 weighted images and FLAIR sequences (normal-5 to 25 µg/dl) and very high ACTH values-6390 pg/ml in bilateral posterior parietooccipital , splenium of (normal < 46.00 pg/ml). He was diagnosed to have Addison’s corpus callosum, cerebellar white matter, internal capsules, middle disease and was started on steroid replacement therapy cerebellar peduncles, mid brain and pons and marked atrophy of (prednisolone 5.0 mg morning and 2.5 mg evening with the brainstem and cerebellum [Figures 1 and 2]. MRI of the fludrocortisone 0.1 mg/day) resulting in dramatic improvement cervicodorsal spine showed atrophy of the dorsal cord with in skin hyperpigmentation. For the last six years he started having hyperintense signals on axial dorsal cuts. Plasma very long chain hesitancy and later developed increased urinary frequency, fatty acids (VLCFAs), C26:0 (0.830 µg/ml) and ratios of C26:0/ urgency and urge incontinence. For the last four years he also C22:0 (0.069) and C24:0/C22:0 (1.416) were elevated. (normal had episodes of fecal incontinence and erectile dysfunction. He values of C26:0 – 0.23±0.09 µg/ml, C26:0/C22:0 – 0.01± 0.004 developed broad based ataxic gait, slurred speech with mild and C24:0/C22:0 – 0.84±0.10, Sir Ganga Ram Hospital, New tremulousness while writing for the last two and a half years. Delhi, India).

Sudesh Prabhakar Department of Neurology, PGIMER, Chandigarh - 160 012, Punjab, India. E-mail: [email protected]

Neurology India | June 2006 | Vol 54 | Issue 2 195 CMYK195 Mishra et al.: Atypical features in a patient with X- linked adrenoleukodystrophy

variants. Rare forms of presentations might mimic spinocerebellar degeneration,[4] olivopontocerebellar atrophy[5] or a brain tumor. Our case presented with cerebellar, autonomic, pyramidal and extrapyramidal features resembling spinocerebellar degeneration. To the best of our knowledge there are reports of 15 cases of adrenoleukodystrophy presenting like spinocerebellar degeneration or olivopontocerebellar atrophy in the world literature. Recently, a novel point mutation (single nucleotide deletion in exon 2) of the ALD gene has been identified in patients presenting like spinocerebellar degeneration.[6] We could find out only two reports of adrenoleukodystrophy from India, presenting as adrenomyeloneuropathy.[7,8] Extrapyramidal manifestations in adrenoleukodystrophy are distinctly rare. We could locate only one case of truncal dystonia as a part of the manifestation of severe childhood cerebral phenotype is reported in world literature.[9] Figure 1: Axial MRI picture (FLAIR image) showing bilateral deep CT and MRI findings have been reported in a similar case parietooccipital white matter hyperintensities labeled ataxic variant of adrenoleukodystrophy.[10] CT revealed marked atrophy of the cerebellum and pons and bilateral low- density lesions in the deep while matter of the cerebellum. MRI showed these lesions more clearly, as well as other lesions in the middle and superior cerebellar peduncles, despite the absence of cerebral white matter involvement at the time of presentation. Management of these patients includes steroid replacement, Lorenzo’s oil, marrow transplantation and . Lorenzo’s oil has been found to reduce the risk of developing MRI abnormalities in asymptomatic boys with normal MRI brain. Bone marrow transplantation is recommended for patients with mild but progressive neurological and MRI abnormalities in childhood cerebral phenotype. This case highlights the need for Figure 2: Mid-sagittal MRI picture (FLAIR sequence) showing atrophy of the brainstem and cerebellum appropriate screening of all male patients with Addison’s disease for adrenoleukodystrophy and the need to keep high index of With these clinical and investigation findings diagnosis of suspicion for the diagnosis of such patients because of its varied adrenoleukodystrophy was made and patient was continued on neurological manifestations. steroid replacement therapy. Patient could not afford mutational analysis. We wish to report this patient because of several peculiar References features like predominant cerebellar and autonomic manifestations, extrapyramidal features and onset with Addison’s 1. Moser HW. Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. Brain 1997;120:1485-508. disease only phenotype with slow evolution to spinocerebellar 2. Van Geel BM, Assies J, Wanders RJ, Barth PG. X-Linked adrenoleukodystrophy: degeneration like presentation. clinical presentation, diagnosis and therapy. J Neurol Neurosurg Psychiatr 1997;63:4-14. 3. Van Geel BM, Bezman L, Loes DJ, Moser HW, Raymond GV. Evolution of phenotypes Discussion in adult male patients with X-Linked adrenoleukodystrophy. Ann Neurol 2001;49:186-94. 4. Nakazato T, Sato T, Nakamura T, Tsuji S, Narabayashi H. Adrenoleukodystrophy Adrenoleukodystrophy is a disorder of peroxisomal metabolism. presenting as spinocerebellar degeneration. Eur Neurol 1989;29:229-34. 5. Vianello M, Manara R, Betterle C, Tavolato B, Mariniello B, Giometto B. X-linked The gene (ABCD1) responsible for the disease is located on Xq28. adrenoleukodystrophy with olivopontocerebellar atrophy. Eur J Neurol This gene codes for a peroxisomal membrane protein, which 2005;12:912-4. 6. Dunne E, Hyman NM, Huson SM, Nemeth AH. A novel point mutation in X-linked facilitates beta-oxidation of VLCFAs. Defect in the gene leads to adrenoleukodystrophy presenting as a spinocerebellar degeneration. Ann Neurol abnormal membrane protein and thus defective degradation of 1999;45:652-5. [2] 7. Mehndiratta MM, Rao KB, Garg S, Pandey S. Adrenomyeloneuropathy. J Assoc VLCFAs, which are responsible for the disease. Physic India 2005;53:562-3. Adrenoleukodystrophy is an important cause of Addison’s disease 8. Singhal BS. : Indian Scenario. Indian J Pediatr 2005;72:315-8 [2] 9. Shinga Y, Siato H, Mochizuki H, Chida K, Tsuburaya K. A case of (4 to 63% in various series), specially in young males. Upto adrenoleukodystrophy having progressed from the frontal lobes. Rinsho 14% patients of XALD may initially present as Addison’s disease Shinkeigaku 1992;32:600-5. 10. Kusaka H, Imai T. Ataxic variant of adrenoleukodystrophy: MRI and CT findings. only phenotype and gradually evolve into one or the other J Neurol 1992;239:307-10. phenotype, usually adrenomyeloneuropathy.[3] Besides, six usual phenotypes there are reports of several atypical Accepted on 06-03-2006

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