Rare Variant of GM2 Gangliosidosis through Activator-Protein Deficiency

Abstract

GM2 gangliosidosis, AB variant, is a very rare form of GM2 gangliosidosis due to a deficiency of GM2 activator protein. We report on two patients with typical clinical features suggestive of GM2 gangliosidosis, but normal results for hexosaminidase A and hexosaminidase B as well as their corresponding genes. Genetic analysis of the gene encoding the activator protein, the GM2A gene, elucidated the cause of the disease, adding a novel mutation to the spectrum of GM2 AB variant. This report points out that in typical clinical constellations with normal enzyme results, genetic diagnostic for activator protein defects should be performed.

Keywords

sphingolipidoses - GM2 gangliosidosis - activator protein - Tay–Sachs' disease

• References

• 1 Sandhoff K, Harzer K. Gangliosides and gangliosidoses: principles of molecular and metabolic pathogenesis. J Neurosci 2013; 33 (25) 10195-10208
• 2 Schepers U, Glombitza G, Lemm T , et al. Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant. Am J Hum Genet 1996; 59 (5) 1048-1056
• 3 Sheth J, Datar C, Mistri M, Bhavsar R, Sheth F, Shah K. GM2 gangliosidosis AB variant: novel mutation from India - a case report with a review. BMC Pediatr 2016; 16 (1) 88
• 4 Salih MA, Seidahmed MZ, El Khashab HY , et al. Mutation in GM2A Leads to a Progressive Chorea-dementia Syndrome. Tremor Other Hyperkinet Mov (N Y) 2015; 5: 306
• 5 Wright CS, Li SC, Rastinejad F. Crystal structure of human GM2-activator protein with a novel beta-cup topology. J Mol Biol 2000; 304 (3) 411-422
• 6 Chen B, Rigat B, Curry C, Mahuran DJ. Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2. Am J Hum Genet 1999; 65 (1) 77-87
• 7 Renaud D, Brodsky M. GM2-gangliosidosis, AB variant: clinical, ophthalmological, MRI, and molecular findings. JIMD Rep 2016; 25: 83-86
• 8 Steenweg ME, Vanderver A, Blaser S , et al. Magnetic resonance imaging pattern recognition in hypomyelinating disorders. Brain 2010; 133 (10) 2971-2982
• 9 Seshadri R, Christopher R, Arvinda HR. Teaching NeuroImages: MRI in infantile Sandhoff disease. Neurology 2011; 77 (5) e34
• 10 Sharma S, Sankhyan N, Kalra V, Garg A. Thalamic changes in Tay-Sachs' disease. Arch Neurol 2008; 65 (12) 1669
• 11 Imamura A, Miyajima H, Ito R, Orii KO. Serial MR imaging and 1H-MR spectroscopy in monozygotic twins with Tay-Sachs disease. Neuropediatrics 2008; 39 (5) 259-263
• 12 Aydin K, Bakir B, Tatli B, Terzibasioglu E, Ozmen M. Proton MR spectroscopy in three children with Tay-Sachs disease. Pediatr Radiol 2005; 35 (11) 1081-1085