BH(4)-deficient hyperphenylalaninemia in Russia

A timely detection of patients with tetrahydrobiopterin (BH(4)) -deficient types of hyperphenylalaninemia (HPABH(4)) is important for assignment of correct therapy, allowing to avoid complications. Often HPABH(4) patients receive the same therapy as phenylalanine hydroxylase (PAH) -deficiency (phenylketonuria) patients—dietary treatment—and do not receive substitutive BH(4) therapy until the diagnosis is confirmed by molecular genetic means. In this study, we present a cohort of 30 Russian patients with HPABH(4) with detected variants in genes causing different types of HPA. Family diagnostics and biochemical urinary pterin spectrum analyses were carried out. HPABH(4)A is shown to be the prevalent type, 83.3% of all HPABH(4) cases. The mutation spectrum for the PTS gene was defined, the most common variants in Russia were p.Thr106Met—32%, p.Asn72Lys—20%, p.Arg9His—8%, p.Ser32Gly—6%. We also detected 7 novel PTS variants and 3 novel QDPR variants. HPABH(4) prevalence was estimated to be 0.5–0.9% of all HPA cases in Russia, which is significantly lower than in European countries on average, China, and Saudi Arabia. The results of this research show the necessity of introducing differential diagnostics for HPABH(4) into neonatal screening practice.