Sapropterin Dihidroklorid Tedavisi Başlanan Hiperfenilalaninemili Hastaların Izlem Sonuçları

Abstract

Phenylketonuria is one of the most commonly seen inborn errors of metabolism that if left untreated causes mental retardation. Until ten years ago, protein and phenylalanine-restricted diet was the only therapeutic option for this disorder. More recently, some of the PAHdeficient patients was found to be responsive to a synthetic analog of BH4 which is the natural cofactor of the enzyme phenylalanine hydroxylase (PAH). In these patients, blood Phe levels decrease with the administration of BH4 and thus more liberal diet could be used while on BH4. Description of such cases has proved that BH4 might be an alternative to low-protein and low-Phe diet. In order to select potentially BH4 responsive PAH-deficient patients a BH4 loading test is necessary. In this study, long-term followup results of hyperphenylalaninemic patients loaded with BH4 and treated with BH4 alone or BH4 along with relaxed diet were presented. A total of 131 patients with hyperphenylalaninemia were evaluated both clinically and biochemically and were categorized to be “more likely responders”. A hundred and twenty two of them were tested for BH4 responsiveness. Patients’ ages ranged from 0 to16 years. Sapropterine dihydrocloride treatment was started in 54 of 63 responders. The age range was between 0-14 years in the treated group. A total of 28 patients were male and 26 were female. Duration of the treatment ranged from 2 to 25 months. Phenylalanine tolerance increased from 7 to 148 mg/kg corresponding to 1.2-6.6 folds increase in daily phe intake as compare to their previous diet. BH4 treatment in five patients was stopped because of secondary unresponsiveness in the course of treatment. No adverse/side events was reported. In conclusion, sapropterin dihydrochloride which is the first drug with FDA approval in the pharmacotherapy of hyperphenylalaninemia seems to be a promising and safe molecule to be used in well-selected responsive patients with PAH deficiency.