Large-Scale Epidemiological Data on the Regional Prevalence of Sphingolipidoses Across India

Background: Sphingolipidoses are a group of lysosomal storage disorders (LSDs) caused by defects in specific lysosomal enzymes that are required for the catabolism of sphingolipids containing ceramide. Objective: To estimate the prevalence of sphingolipidoses and their regional distribution as the epidemiological data is scarce from India. Methods: This is a retrospective study of 5029 patients with clinical suspicion of various lysosomal storage disorders enrolled during the period of July 2008 to June 2023. Enzyme analysis was performed to confirm the diagnosis. Plasma chitotriosidase was estimated as a surrogate biomarker in cases with Gaucher and Niemann Pick A/B disease. Results: In general, 29.2% (1469/5029) of the cases tested positive for LSD, of which 54% were for Sphingolipidoses. Among Sphingolipidoses (n=793), the relative frequency of Gaucher disease (19.2%) is higher followed by Metachromatic Leukodystrophy (18.2%). The age of onset showed a positive association with the percentage of specific enzyme activity in GM1-gangliosidosis (r = 0.529, p <0.00001), Niemann Pick A&B (r = 0.443, p = 0.00004), Metachromatic Leukodystrophy (r = 0.169, p = 0.042) and Krabbe (r = 0.371, p = 0.00003). The prenatal diagnosis revealed ~20.8% of positivity for Sphingolipidoses. Affected cases exhibited a high degree of consanguinity (35.4%). Conclusion: Our study demonstrates the highest prevalence of Gaucher disease and Metachromatic leukodystrophy among all the lysosomal storage disorders. Estimated relative frequency of Sphingolipidoses zonal wise in India. Disease-specific thresholds were established in differentiating affected vs carriers.