First Brazilian birth after Preimplantation Genetic Testing for Severe Methylmalonic Acidemia: preventing sudden...

Methylmalonic acidemia (MMA) is a rare autosomal recessive metabolic disorder caused by pathogenic variants in the MMUT gene, often associated with severe neonatal manifestations and sudden unexpected death in infancy (SUDI). Preimplantation Genetic Testing for Monogenic Diseases (PGT-M) offers a valuable reproductive option for at-risk couples seeking to prevent transmission of such conditions. This represents the first Brazilian case of a healthy birth following combined PGT-M and PGT-A for MMA known. After the neonatal loss of their first child due to mut0-type MMA, a couple underwent genetic testing, which identified compound heterozygosity in MMUT: a maternal deletion (c.1196_1197del) and a paternal duplication (c.213_216dup). Haplotype construction used parental and proband DNA. Two IVF cycles yielded 13 blastocysts; of these, one embryo was diagnosed as being both euploid and unaffected, and two were euploid and heterozygous carriers. One of those embryos was selected for transfer, resulting in an uneventful pregnancy and the live birth of a healthy female infant. This single case highlights the clinical utility of PGT-M to prevent the recurrence of a severe inborn errors of metabolism and underscores the importance of early genetic counseling in couples with prior adverse neonatal outcomes.