GM2-Gangliosidosis, AB Variant: Clinical, Ophthalmological, MRI, and Molecular Findings

Abstract

GM2-gangliosidosis, AB variant is a very rare form of GM2 gangliosidosis due to a deficiency of GM2 activator protein, associated with autosomal recessive mutations in GM2A. Less than ten patients, confirmed by molecular analysis, have been described in the literature.A 12-month-old Hmong girl presented to the neurometabolic clinic for evaluation of global developmental delay, hypotonia, and cherry red spots. The parents were not known to be consanguineous. Her examination was remarkable for hypotonia with hyperreflexia and excessive startling. The head circumference was normal. An extensive neurometabolic evaluation was negative.Developmental regression began at 14 months of age. Retinal examination at 16 months of age disclosed 4+ cherry red/black spots with "heaped up" ring of whitish infiltrate surrounding both foveae but no evidence of optic atrophy or peripheral retinal abnormalities. Repeat magnetic resonance imaging (MRI) scan at 17 months of age revealed delayed but interval myelination associated with abnormal signal intensity of the bilateral thalami presenting as T2 hyperintensity of the posterior thalami in the region of the pulvinar nuclei and T2 hypointensity in the anterior thalami. Sequencing of the GM2A gene revealed a homozygous c.160 G>T mutation, predicted to result in a premature protein termination p. Glu54*.

Rare Variant of GM2 Gangliosidosis through Activator-Protein Deficiency

“…6 Renaud et al showed delayed myelination and hyperintensity of the posterior thalami in the region of the pulvinar nuclei. 7 Similar changes have been reported for classical gangliosidosis, especially in the basal ganglia, but also in the thalamus [8][9][10] as well as periventricular white matter. 11,12 These signs were also seen in our patients, both of which showed signal changes in the basal ganglia and some myelination delay: one showed signal changes of periventricular white matter and the other some signal changes of the posterior thalami at 14 months.…”

GM2 activator protein deficiency, mimic of Tay-Sachs disease

“…It is an extremely rare disease and only 16 cases have been reported so far, of which 9 cases only are proven by molecular studies (Table 1). [3][4][5][6][7][8][9][10][11]…”

“…Comparison of present case with previous proven cases. 3-11 Schroder et al,1991, Xie et al, 1992 Schroder et al, 1993 5 Schepers et al, 1996 6 Schepers et al, 1996 6 Chen et al, 1999 7 Kolodny et al, 2008 8 Renaud et al, 2015 9 Kustermann et al, 2015 10 Sheth et al…”

“…1,2 Only 16 patients with GM2 Activator protein deficiency have been reported so far and the underlying mutation was proven in only 9 cases. [3][4][5][6][7][8][9][10][11] We report a homozygous intronic mutation proven case of GM2 activator protein deficiency which is the 10th case report proven by molecular studies.…”

Insilico Analysis Reveal Three novel nsSNPs May effect onGM2Aprotein Leading to AB variant of GM2 gangliosidosis

“…(10, 11) located in chromosome 5q31.3-q33.1 (12)(13)(14) The GM2 activator deficiency is caused by mutations in the GM2A gene encoding the GM2 activator protein. (15) Different mutations have been reported related to GM2A, (16)(17)(18)(19)(20)(21)(22) but interestingly, some study shows that, mutation in GM2A Leads to a Progressive Chorea-dementia Syndrome. (23) ELISA system can be used as diagnosis tool as well as therapeutic evaluation of GM2 gangliosidoses using anti-GM2 ganglioside antibodies (24) Can also be diagnosed by demonstrating accumulation of GM2 in the CSF of patients with normal hexosaminidase activity.…”