Биохимическая и молекулярно-генетическая характеристика 16 пациентов с пропионовой ацидемией

Propionic acidemia is a rare autosomal recessive metabolic disorder, characterized as classic organic acidemia. The article represents biochemical and molecular characterization of 16 patients diagnosed with propionic acidemia in Russia. Symptoms appeared during the first months after birth in most cases. Poor feeding, seizures, hypotonia, lethargy were the most frequent symptoms. Biochemical tests (GC-MS and MS/MS) showed elevated 3-hydroxypropionic acid, methylcitrate, propionylglycine, C3 in patients blood. Six undescribed earlier variants were found as a result of PCCA & PCCB (4 variants - PCCA, 2 - PCCB) genes DNA-tests. Variant c.655-2A>G in PCCB is the most frequent in this group (17.2%). Localization of missense variants and their effect on protein was demonstrated using propionyl-CoA carboxylase 3D model. New variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines.