GM2 Gangliosidosis AB Variant: A Hidden Truth

GM2 gangliosidosis AB variant (GM2AB) is a rare neurodegenerative lysosomal storage disorder with clinical features resembling Tay-Sachs disease but characterized by normal lysosomal β-hexosaminidase A enzyme activity. To date, only 14 cases of the acute infantile form have been reported. To the best of our knowledge, this is the first case of GM2AB in a Portuguese patient reported in the literature. We describe the case of a girl with GM2AB, whose clinical presentation and pathological findings were critical for diagnosis. Post-mortem genetic sequencing identified a pathogenic mutation in homozygosity in the GM2A gene, confirming the diagnosis. This case highlights the importance of considering GM2AB in patients with severe neurodegenerative phenotypes and typical pathological findings, even when enzymatic studies are normal. Preserving genetic material post-mortem may allow for diagnosis even years after death, providing critical insights into rare disorders.