Prenatal Diagnosis of Organic Acidemias – Experience from a Tertiary Care Hospital in India

Abstract Background: In India, the tradition of marriages, largely confined to the same ethnic groups or within families, increases the proportion of autosomal recessive genetic disorders. This includes organic acidemias (OAs) too. With immense burden of treatment of these disorders, the uptake of prenatal diagnosis (PND) is high. We present our experience in PND for the common five OAs, namely methylmalonic acidemia (MMA), propionic acidemia (PA), glutaric acidemia type 1 (GA1), isovaleric acidemia (IVA), and maple syrup urine disease (MSUD). Objective: The objective of this study was to describe the spectrum and our experience in PND for five common OAs from our center. Materials and Methods: Pregnant women with previous children affected with any of five OAs, undergoing prenatal diagnostic testing were enrolled, from 2008 to 2023. PND was performed using targeted molecular testing on either chorionic villous sampling or amniotic fluid samples. The pathogenicity of all variants and results of PND was analyzed. Results: Among 57 families undergoing 80 PNDs, genetic confirmation was achieved in 41 via proband. Parental testing confirmed molecular diagnosis in further 16 families. PA emerged as the most common disorder with 28 PNDs, followed by 21 of MMA, 18 of MSUD, 10 PNDs of GA1 cases, and 3 from IVA families. Affected fetuses were observed in 22 pregnancies. One family with previous MSUD was noted with a second disorder related to CANT1 . Conclusion: PND is a feasible and effective method of prevention of the burdensome organic acidemias in our population.