Clinical, biochemical and molecular spectrum of acute neuronopathic type 2 Gaucher disease from India

Abstract Background Gaucher disease (GD) is one of the most common lysosomal storage disorders, and has three clinical subtypes (Type 1, 2 and 3). Of the three subtypes, type 2 GD (GD2), also referred to as acute infantile neuronopathic GD is the most severe type. It is characterized by early and profound central nervous system involvement, and patients succumb to disease before two years of age due to severe neurological deterioration and associated complications. It is the rarest of the three subtypes with a reported proportion of C (p.Leu483Pro) was identified in a compound heterozygous state in majority cases ( n = 10/19). Furthermore, we also identified a rare recurrent missense variant c.371T > G (p.Met124Arg) in exon 4 of the GBA1 gene in 4 patients with GD2 from Gujarat, suggesting the possibility of a founder effect. Computational protein modeling and in-silico analysis predicted a destabilizing effect on GBA1 protein structure and stability. Conclusion Overall, the present study represents the largest case series of type 2 Gaucher disease reported from India to date and provides important insights into its clinical and molecular spectrum in the Indian population.