Clinical and genetic characteristics of hyperphenylalaninemia cases identified in the Ivanovo region as part of expanded neonatal screening

Abstract

The clinical and genetic characteristics of 9 cases of hyperphenylalaninemia (HРA) identified during the extended neonatal screening (RNC) for the period 2023-2024 are presented. With confirmatory diagnosis using tandem mass spectrometry and molecular genetic analysis of HPA-associated genes, 5 children were diagnosed with severe HPA and 4 with mild HPA. All patients with severe HPA had mutations in the PAH gene: a frequent mutation C.1222C>T in the homo or hemizygous state (in 3 children), a combination of two pathogenic nucleotide variants in the compound heterozygous state (in 2 children). Three children with mild HPA had mutations in the PAH gene in a compound heterozygous state: a frequent mutation and a rare one (1 child); a frequent mutation and a mutation with unknown clinical significance (1 child), two rare mutations (1 child). One child with mild HPA had 2 mutations in the PTS gene in a compound heterozygous state. All children (both with severe HPA receiving treatment and with mild HPA, have.