BH₄-deficient hyperphenylalaninemia in Russia

by Polina Gundorova, Irina A. Kuznetcova, Galina V. Baydakova, Anna A. Stepanova, Yulia S. Itkis, Victoria S. Kakaulina, Irina P. Alferova, Lidya V. Lyazina, Lilya P. Andreeva, Ilya Kanivets, Ekaterina Y. Zakharova, Sergey I. Kutsev, Aleksander V. Polyakov

A timely detection of patients with tetrahydrobiopterin (BH₄) -deficient types of hyperphenylalaninemia (HPABH₄) is important for assignment of correct therapy, allowing to avoid complications. Often HPABH₄ patients receive the same therapy as phenylalanine hydroxylase (PAH) -deficiency (phenylketonuria) patients—dietary treatment—and do not receive substitutive BH₄ therapy until the diagnosis is confirmed by molecular genetic means. In this study, we present a cohort of 30 Russian patients with HPABH₄ with detected variants in genes causing different types of HPA. Family diagnostics and biochemical urinary pterin spectrum analyses were carried out. HPABH₄A is shown to be the prevalent type, 83.3% of all HPABH₄ 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. HPABH₄ 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 HPABH₄ into neonatal screening practice.