Estimation of the global burden of autosomal recessive rare inborn errors of metabolism

While many Rare Inborn Errors of Metabolism are treatable conditions their optimal diagnosis and treatment is a challenge for nations with low resources. Moreover, the population prevalence of these conditions is largely unknown. The availability of large genomic datasets brings the opportunity to estimate population carrier frequency of autosomal recessive IEMs. This would help to generate diseases burden statistics for better allocation of resources. In the current work we estimated the gene specific combined minor allele frequency of pathogenic variants from the gnomAD dataset for 235 genes associated with IEM phenotypes in OMIM. As per our estimation almost one third of the Global population is carrier for a pathogenic variant responsible for rare autosomal recessive inborn error of metabolism with the highest carrier frequency in the Ashkenazi Jews. Globally per thousand live births approximately five children are born with an ARIEM. European Finnish have the highest burden of nine out of 10,000 live births. With 25 million live births per year India is expected to have at least 8,025 newborns with an ARIEM. Since many of these diseases are treatable early newborn screening holds the key to ensure optimal management of these children.