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   Introduction
   Case Report
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 Table of Contents    
CASE REPORT  
Year : 2016  |  Volume : 58  |  Issue : 4  |  Page : 467-470
A case of adrenoleukodystrophy presenting with manic symptoms in a patient on steroids for Addison's disease


1 Department of Psychiatry, Government Medical College, Thrissur, Kerala, India
2 Department of Health Services, Primary Health Centre Arthat, Thrissur, Kerala, India

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Date of Web Publication27-Dec-2016
 

   Abstract 

Adrenoleukodystrophy (ALD) is an X-linked disorder with diverse clinical presentations. A 30-year-old male, previously diagnosed with Addison's disease, on steroid supplementation for 18 years, presented to us with manic symptoms for 4 years. He was found to have white matter hypodensities in computed tomography head and had white matter signal changes in magnetic resonance imaging, and therefore a diagnosis of ALD was made.

Keywords: Adrenoleukodystrophy, Addison's disease, organic mood disorder, peroxisomal disorders

How to cite this article:
Jyothi K S, George C, Shaji K S. A case of adrenoleukodystrophy presenting with manic symptoms in a patient on steroids for Addison's disease. Indian J Psychiatry 2016;58:467-70

How to cite this URL:
Jyothi K S, George C, Shaji K S. A case of adrenoleukodystrophy presenting with manic symptoms in a patient on steroids for Addison's disease. Indian J Psychiatry [serial online] 2016 [cited 2019 Dec 14];58:467-70. Available from: http://www.indianjpsychiatry.org/text.asp?2016/58/4/467/196705



   Introduction Top


Adrenoleukodystrophy (ALD) is an X-linked recessive disorder due to mutations in the ABCD1 gene in X-chromosome, characterized by impaired peroxisomal beta-oxidation of very long-chain fatty acids (VLCFA), resulting in its accumulation in plasma and all tissues, especially affecting the adrenal glands, white matter of nervous system, and Leydig cells of testes. It is the most common peroxisomal disorder, with a prevalence of about 1 in 20,000.[1],[2] The disease can present with diverse clinical manifestations, posing a diagnostic challenge, and sometimes atypical psychiatric symptoms may be the clinical presentation.


   Case Report Top


Our patient is a 30-year-old unmarried male, construction worker, with no prior history of any psychiatric illness. He was taking prednisolone 7.5 mg daily for the past 18 years after being diagnosed with Addison's disease by an endocrinologist, and was functioning well till about 4 years back.

He was brought to the psychiatry department by his mother with a history of continuous manic symptoms for the past 4 years. He was having increased talk, increased self-esteem, over familiar behavior, irritability, overspending, irregularity in job, and sleep disturbance. His mother also reported that he was recklessly driving his motorbike and has fallen a few times. He was also disturbing girls and children in public places. There were no psychotic symptoms or history of substance abuse.

On further inquiry, his relatives had noticed him to be less stronger physically, compared to before, during the past 1 year. He had an accident 6 months back during work when he dropped a stone and fractured his left forearm which was surgically treated.

There was a family history of rapidly progressing paralysis and death in his brother and cousin at 9 and 12 years of age, respectively. The latter also had a history of receiving steroid supplementation during the illness.

The patient was not very cooperative for a detailed assessment initially. His vitals were normal. He was very jovial but became irritable at times. His talk and psychomotor activity was increased. Insight and judgment were poor. His cognitive functions were normal.

On initial investigation, his serum cholesterol and low-density lipoprotein were elevated (267 and 193). Hemogram, electrolytes, and sugar were normal. Liver, renal, and thyroid function tests were normal. Serological tests for HIV and venereal disease research laboratory were negative. Ultrasound scan of the abdomen showed minimal fatty infiltration of the liver.

Because of the atypical nature of the presentation–prolonged manic symptoms appearing many years after steroid replacement was started–we opted for a computed tomography scan of the brain. It showed white matter hypodensities involving centrum semiovale [Figure 1], pareito-occipital region, and cerebellum bilaterally [Figure 2].
Figure 1: Computed tomography brain showing white matter hypodensities involving centrum semiovale

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Figure 2: Computed tomography brain showing bilateral cerebellar hypodensities

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Hence, we did an magnetic resonance imaging (MRI) of the brain which showed bilateral fairly symmetrical T2/FLAIR white matter hyperintensities involving deep white matter and periventricular region, sparing subcortical U-fibers, involving pareito-occipital region [Figure 3]. Similar signal changes were also noted along corticospinal tracts (in brainstem, crus of midbrain, cerebral peduncle and pons), lateral thalami, splenium of corpus callosum, middle and inferior cerebellar peduncles, and dentate nuclei of cerebellum [Figure 4]. No abnormal parenchymal enhancement was noted in the postcontrast study.
Figure3: Magnetic resonance imaging of the brain showing bilateral fairly symmetrical T2/FLAIR white matter hyperintensities involving deep white matter and periventicular region, sparing subcortical U-fibers

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Figure 4: Magnetic resonance imaging of the brain showing bilateral T2/FLAIR white matter hyperintensities involving corticospinal tracts, middle and inferior cerebellar peduncles, and dentate nuclei of cerebellum

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A diagnosis of ALD was made. A psychiatric diagnosis of organic mood disorder (mania) was also made. We were unable to do a VLCFA estimation as it is not available in our locality.

Meanwhile, the patient was already started on sodium valproate 600 mg daily and it was hiked to 1000 mg daily. However, the patient developed significant ataxia, so sodium valproate was reduced and stopped and he was managed on haloperidol. With 20 mg/day of haloperidol, his manic symptoms were fairly controlled. His young mania rating dropped to 14 from an initial 33 over a period of 2 weeks.

When the patient became more cooperative, a neurological assessment was made, and he was found to have cerebellar ataxia and incoordination. He had hypotonia in the upper limbs, but muscle tone was increased in the lower limbs. Deep tendon reflexes were brisk. Weakness with Grade 4 power was noted on all limbs. Ophthalmic fundus examination was normal. His cognitive functions were normal.


   Discussion Top


Addison's disease is a fairly common condition, and the common psychiatric manifestation associated with it is depression.[3] During administration of steroids, manic symptoms may occur initially, especially with high doses.[4] Chronic use of steroids may lead to the development of depressive symptoms.[5] However, our patient had developed manic symptoms–which was continuous in nature–even though he was getting only a low dose of prednisolone for quite a long time. These atypical features prompted us for the detailed investigation and led to the diagnosis of ALD.

ALD is an X-linked peroxisomal disorder due to mutations in the ABCD1 gene in X chromosome, characterized by impaired peroxisomal beta-oxidation of VLCFA.[6] The disease is associated with multiple phenotypes which can present along a varying age spectrum with considerable clinical diversity.[7]

The childhood-onset form of ALD is a rapidly progressing neurodegenerative disease which will result in death in almost 2 years. It may start from 3 to 8 years of age and is characterized by attention deficit, intellectual problems, behavioral problems, and neurological symptoms. An adolescent-onset form is also described, in which death occurs about 2 years following the onset of neurological symptoms. An adult-onset less severe form is also described.[2],[6]

Any combination of symptoms–adrenal, gonadal, neurologic, or psychiatric–is possible in ALD and it can produce a diagnostic dilemma although the most common presentation is neurological.

An MRI of brain shows the characteristic changes–bilateral symmetrical involvement of deep white matter in the parieto-occipital lobes, periventricular region, and the splenium of the corpus callosum–in most cases. A contrast MRI is also helpful in assessing the disease progression.[8] Diagnosis may be confirmed by demonstration of elevated plasma levels of VLCFAs.

There is no very promising treatment options for ALD so far. Dietary restriction of VLCFAs has not demonstrated any significant clinical efficacy. Dietary supplementation with “Lorenzo's oil” may slow the disease progression if done early. Bone marrow transplantation can halt the disease progression if done sufficiently early in the course, but is of little use in advanced cases. Addison's disease can be managed by appropriate supplementation with exogenous steroids.[1],[9]

There is a clear lack of literature regarding the management of psychiatric manifestations of ALD. Lithium can precipitate minerelocorticoid deficiency in these patients.[1] We observed that valproate is associated with significant ataxia in our patient. Atypical antipsychotics may worsen the lipid profile and may cause metabolic syndrome. These issues pose challenges in the management of psychiatric symptoms.


   Conclusion Top


It is of immense importance to suspect and detect ALD in patients presenting with Addison's disease and psychiatric symptoms, rather than considering it as mere psychiatric manifestations of Addison's disease and steroid use. This can help in the early initiation of specific treatments which may limit the disease progression and improve life expectancy of patients with ALD. Moreover, it will help in genetic counseling and early detection of susceptible individuals in the family.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Rosebush PI, Garside S, Levinson AJ, Mazurek MF. The neuropsychiatry of adult-onset adrenoleukodystrophy. J Neuropsychiatry Clin Neurosci 1999;11:315-27.  Back to cited text no. 1
    
2.
Engelen M, Kemp S, de Visser M, van Geel BM, Wanders RJ, Aubourg P, et al. X-linked adrenoleukodystrophy (X-ALD): Clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis 2012;7:51.  Back to cited text no. 2
    
3.
Rebecca E, Patricia I, Michael F. The neuropsychiatric profile of Addison's disease: Revisiting a forgotten phenomenon. J Neuropsychiatry Clin Neurosci 2006;18:450-9.  Back to cited text no. 3
    
4.
Ur E, Turner TH, Goodwin TJ, Grossman A, Besser GM. Mania in association with hydrocortisone replacement for Addison's disease. Postgrad Med J 1992;68:41-3.  Back to cited text no. 4
    
5.
Fardet L, Petersen I, Nazareth I. Suicidal behavior and severe neuropsychiatric disorders following glucocorticoid therapy in primary care. Am J Psychiatry 2012;169:491-7.  Back to cited text no. 5
    
6.
Kemp S, Berger J, Aubourg P. X-linked adrenoleukodystrophy: Clinical, metabolic, genetic and pathophysiological aspects. Biochim Biophys Acta 2012;1822:1465-74.  Back to cited text no. 6
    
7.
Berger J, Forss-Petter S, Eichler FS. Pathophysiology of X-linked adrenoleukodystrophy. Biochimie 2014;98:135-42.  Back to cited text no. 7
    
8.
Antonio CR, Gislaine CL, Fabio H, Ricardo N. Adult-onset adrenoleukodystrophy presenting as a psychiatric disorder. MRI findings. Dement Neuropsychol 2012;6:290-5.  Back to cited text no. 8
    
9.
Moser HW. Therapy of X-linked adrenoleukodystrophy. NeuroRx 2006;3:246-53.  Back to cited text no. 9
    

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Correspondence Address:
Cyriac George
Department of Health Services, Primary Health Centre Arthat, Chittanjoor P. O, Thrissur - 680 523, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5545.196705

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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