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|Year : 2017 | Volume
| Issue : 5 | Page : 1195-1196
Isolated globus pallidi hypointensities in type 2 GM1 gangliosidoses
Mahesh Kamate, Nishant Mittal
Department of Paediatrics, KLE University's J N Medical College, Belgaum, Karnataka, India
|Date of Web Publication||6-Sep-2017|
Department of Paediatrics, KLE University's J N Medical College, Belgaum - 590 010, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kamate M, Mittal N. Isolated globus pallidi hypointensities in type 2 GM1 gangliosidoses. Neurol India 2017;65:1195-6
An 8-year old boy, born to consanguineous parents, presented with developmental delay, unclear speech, abnormal gait, and recent worsening in gait and swallowing function. There was no dysmorphic features or hepatosplenomegaly. He had extrapyramidal rigidity with severe dysarthria because of oromandibular dystonia. His two elder sisters had similar problems and were bed-bound from 8 years of age. Routine blood tests, fetoprotein, vitamin E, copper, and ceruloplasmin titers were negative. Metabolic work-up, including blood and urine chromatography of amino acids and urinary organic acids, were unremarkable. A careful look at the magnetic resonance imaging (MRI), which was reported to be normal, revealed that the globus pallidi were hypointense. This MRI picture was more evident on the fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted (DW) images [Figure 1]. There was neither cerebral atrophy nor evidence of white matter hyperintensities. These MRI changes have been reported in late infantile and juvenile GM1 gangliosidoses earlier; however, in view of the rarity of the condition, many may not be aware of this finding. This prompted a genetic testing which showed heterozygous variants in the GLB1 gene (responsible for the production of beta-galactosidase enzyme), known to cause GM1 (monosialotetrahexosylganglioside) gangliosidosis. This included a paternally inherited, novel canonical splice site variant (NM_000404.2:c.(553-2A>G) and a maternally inherited previously reported pathogenic variant [NM_000404.2:c.(1325G>A); NP_000395:p.(Arg442Gln)]. Lysosomal enzyme assay in cultured skin fibroblasts revealed a galactosidase activity of 1.6 nmol/mg/h (normal range: 32.5–206.5 nmol/mg/h).
|Figure 1: Magnetic resonance imaging of the brain: Axial FLAIR (a), spin-echo T2-weighted (b) sequences and coronal (c) sections showing hypointensities in the bilateral globus pallidi (black arrows). The signal changes are more pronounced in the diffusion-weighted images (d). There is neither cerebral atrophy nor a periventricular white matter signal change. The thalami are normal|
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Neurodegeneration with brain iron accumulation, which includes conditions such as pantothenate kinase-associated neurodegeneration, neuroferritinopathy, infantile neuroaxonal dystrophy, and aceruloplasminemia, is characterized by the evidence of focal brain iron accumulation in the extrapyramidal nuclei; the globus pallidum is consistently involved. The age of onset of the symptoms, the involvement of additional nuclei, and the pattern of involvement help in the differentiation of different disorders. Globus pallidum T2 hypointensity is also a known feature of thalassemia major and human immunodeficiency virus, in which the hypointensity is caused by iron deposition, and of Wilson's disease, in which it reflects the paramagnetic properties of copper. Isolated globus pallidum hypointensity in children is always abnormal. It should, therefore, point toward GM1 gangliosidoses and prompt appropriate investigations.
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