Genetic Footprints in El Salvador: Analyzing Five Years of Expanded Newborn Metabolic Screening

Background: Expanded newborn screening (NBS) enables early detection of treatable metabolic disorders, but population-level data from Central America are scarce. The aim of this work is to describe the frequency and spectrum of inherited metabolic disorders detected through an expanded NBS program in El Salvador between February 2020 and October 2025. Methods: A retrospective observational study analyzed 2,308 dried-blood-spot samples obtained primarily within the first week of life from hospitals across the country. Screening included ~70 conditions using tandem mass spectrometry followed by confirmatory targeted DNA analysis. Results: Thirty-two newborns were diagnosed with inherited metabolic or enzymatic disorders (detection rate: 1:72 screened newborns). The most frequent condition was glucose-6-phosphate dehydrogenase deficiency with the c202G>A; 376A>G mutation (n=13; 1:178), followed by maple syrup urine disease (n=6; 1:385) and several organic acidemias acidemias (n= 4; 1:577). The distribution reflects the admixed ancestry characteristic of Latin American populations. Conclusion: Expanded newborn screening is feasible in a Central American middle-income setting and reveals a clinically significant load of treatable disease. Nationwide implementation with structured follow-up care is warranted.