P023: Using genomic databases to estimate rare disease prevalence: Application to disorders of propionyl-CoA oxidation

Inborn errors of propionate metabolism are a group of autosomal recessive, genetically heterogenous, severe and potentially lethal disorders detected via elevated propionylcarnitine on newborn screening (NBS). AAV-gene therapy efforts are underway for isolated methylmalonic acidemia (MMUT, MMAB) and propionic acidemia (PCCA, PCCB), supported by public and private partnerships, including the PaVe-GT and Bespoke Gene Therapy Consortium efforts. Data from NBS studies suggest these conditions should be classified as rare diseases, however, the exact prevalence of each disorder is unknown and complicated by genetic heterogeneity and the lack of a nationwide NBS registry.