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Annals of Indian Academy of Neurology
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LETTERS TO THE EDITOR
Year : 2021  |  Volume : 24  |  Issue : 4  |  Page : 620-622
 

Florid brain calcification in a child with X-linked adrenoleukodystrophy: What does it signify?


1 Pediatric Neurology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Chandigarh, India
2 Senior Research Associate, Pediatric Neurology Unit, Department of Pediatrics, Advanced Pediatrics Centre, PGIMER, Chandigarh, Council of Scientific and Industrial Research, CSIR Complex, Library Avenue, Pusa, New Delhi, India
3 Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh, India

Date of Submission08-Sep-2020
Date of Acceptance03-Nov-2020
Date of Web Publication18-Mar-2021

Correspondence Address:
Dr. Lokesh Saini
Assistant Professor, Pediatric Neurology Division, Department of Pediatrics, Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aian.AIAN_974_20

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How to cite this article:
Bhanudeep S, Madaan P, Saini AG, Vyas S, Saini L. Florid brain calcification in a child with X-linked adrenoleukodystrophy: What does it signify?. Ann Indian Acad Neurol 2021;24:620-2

How to cite this URL:
Bhanudeep S, Madaan P, Saini AG, Vyas S, Saini L. Florid brain calcification in a child with X-linked adrenoleukodystrophy: What does it signify?. Ann Indian Acad Neurol [serial online] 2021 [cited 2021 Oct 25];24:620-2. Available from: https://www.annalsofian.org/text.asp?2021/24/4/620/312835




A seven-year-old boy presented with poor attention span, hyperactivity, and aggression for past one month. There was no history of hearing, vision, speech, and gait disturbances or focal neurological deficits. There was no history of trauma or any similar history in the family. His 4-year-old younger female sibling was apparently healthy and asymptomatic. Generalized hyperpigmentation other than inattention was noticed during examination. Computerized tomography (CT) brain revealed hyperdensities in bilateral parieto-occipital white matter along the trigones of the lateral ventricles with suggestive demyelination in MRI [Figure 1]. With a clinico-radiological possibility of X-linked Adrenoleukodystrophy (X-ALD), the next genetic sequencing confirmed the diagnosis [a hemizygous pathogenic missense variant in exon 9 of the ABCD1 gene (p.Arg660Trp)]. His serum ACTH was 800 pg/ml. Parental testing could not be done due to affordability issues and the parents are not planning for next pregnancy.
Figure 1: Neuroimaging of the index child. Contrast Computed tomography images show calcifications in bilateral parieto-occipital white matter (a, b); T2W MRI images show confluent hyperintense signal intensities in parieto-occipital periventricular white matter (c) and T1W contrast MRI images showing no contrast enhancement (d)

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(X-ALD) is the commonest peroxisomal disorder. The involved ABCD1 gene encodes a peroxisomal membrane protein involved in transmembrane transport of very-long chain fatty acids into the peroxisome, thereby causing cytosolic accumulation in the disease state.[1] Varied clinical phenotypes have been described for ALD with age: Addison-only at school age, childhood, adolescent and adult cerebral ALD, adrenomyeloneuropathy with or without cerebral demyelination in late adulthood, and symptomatic and asymptomatic carriers.[2] Cerebral ALD is an insidious onset (as in the index child), rapidly progressive disorder that presents with deficits in attention and reasoning and may mimic attention deficit hyperactivity disorder.[2] Brain MRI is the preferred imaging modality for the detection of progressive demyelination and evolution of the disease when compared to CT. The classic MRI findings include parieto-occipital white matter (WM) abnormalities with complete sparing of arcuate fibres. On histopathology, three zones have been described- outer active demyelination zone, middle inflammatory zone, and innermost burnt-out zone.[3] Besides, contrast enhancement has a role in determination of progression of the disease. Also, different radiological patterns have been described for X-ALD. These include – the classical parietooccipital WM involvement, frontal WM predominant, isolated involvement of tracts, and cerebellum or a combination of any of these.[4] Many of these patterns are reported with Krabbe disease which is the closest differential diagnosis.[5]

Symmetrical calcifications have been rarely reported in childhood X-ALD. If present, they are often seen in the innermost zone and may be an early sign of progression to inflammatory stage of X-ALD.[1],[2],[6] Intracranial calcifications have also been described in other neurodegenerative disorders such as Cockayne syndrome, Alexander disease, Krabbe disease, mitochondrial cystic leukoencephalopathies, Fabry disease and sulphite oxidase deficiency.[7] Proposed hypothesis for calcium deposition in the brain for different neurological disorders include inflammation and secondary to white matter degeneration (X-ALD, Krabbe disease), microangiopathy (mineralising microangiopathy), dystrophic process (Dural arteriovenous fistula), abnormal calcium metabolism (hypoparathyroidism), etc.[8],[9]

In X-ALD, the calcifications are usually seen around the peritrigonal and periventricular regions.[10] The characteristic location of calcifications in an appropriate clinical setting may aid in narrowing the differential diagnoses. Hence, computerized tomography may help in an early diagnosis of ALD especially in resource constraint settings.

Consent

Written informed consent obtained from parents.

Ethical statement

We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Acknowledgements

Authors thank the parents for images and adding to the literature.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Engelen M, Kemp S, Poll-The BT. X-linked adrenoleukodystrophy: Pathogenesis and treatment. Curr Neurol Neurosci Rep 2014;14:486.  Back to cited text no. 1
    
2.
Ulate-Campos A, Petanas-Argemi J, Rebollo-Polo M, Jou C, Sierra C, Armstrong J, et al. Adrenoleucodistrofia ligada al X con patron radiologico atipico [X-linked adrenoleukodystrophy with an atypical radiological pattern]. Rev Neurol 2018;66:237-40.  Back to cited text no. 2
    
3.
Ferrer I, Aubourg P, Pujol A. General aspects and neuropathology of X-linked adrenoleukodystrophy. Brain Pathol 2010;20:817-30.  Back to cited text no. 3
    
4.
Loes DJ, Fatemi A, Melhem ER, Gupte N, Bezman L, Moser HW, et al. Analysis of MRI patterns aids prediction of progression in X-linked adrenoleukodystrophy. Neurology 2003;61:369-74.  Back to cited text no. 4
    
5.
Michael SN, Madaan P, Jauhari P, Chakrabarty B, Kumar A, Gulati S. Selective pyramidal tract involvement in late-onset Krabbe disease. Indian J Pediatr 2019;86:970-1.  Back to cited text no. 5
    
6.
Inoue Y, Fukuda T, Takashima S, Ochi H, Onoyama Y, Kusuda S, et al. Adrenoleukodystrophy: New CT findings. Am J Neuroradiol 1983;4:951-4.  Back to cited text no. 6
    
7.
Tonduti D, Panteghini C, Pichiecchio A, Decio A, Carecchio M, Reale C, et al. Encephalopathies with intracranial calcification in children: Clinical and genetic characterization. Orphanet J Rare Dis 2018;13:135. doi: 10.1186/s13023-018-0854-y.  Back to cited text no. 7
    
8.
Livingston JH, Stivaros S, Warren D, Crow YJ. Intracranial calcification in childhood: A review of aetiologies and recognizable phenotypes. Dev Med Child Neurol 2014;56:612-26.  Back to cited text no. 8
    
9.
Madaan P, Swamy D, Saini L. Stroke following trivial trauma. Pediatr Neurol 2019;96:83.  Back to cited text no. 9
    
10.
Santosh Rai PV, Suresh BV, Bhat IG, Sekhar M, Chakraborti S. Childhood adrenoleukodystrophy-Classic and variant-Review of clinical manifestations and magnetic resonance imaging. J Pediatr Neurosci 2013;8:192-7.  Back to cited text no. 10
    


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