부산대학교 도서관

Abstract: Background: Whilst a reduction in blood phenylalanine (Phe) levels is essential in patients with PKU, a decrease in Phe/Tyrosine (Tyr) ratio and fluctuations in blood Phe levels over time have been recently associated with improved neuropsychological outcome. The aim of this study was to identify if Tetrahydrobiopterin (BH4) offers additional benefit based on the assumption that these 2 factors are beneficial. Method: Since 2002, 9 patients identified through NBS as BH4 responsive (BH4 group) and 25 non-responsive patients (non-BH4 group) produced a total of 1384 and 4415 samples, respectively, for analysis. Statistical analysis was performed to compare mean and median Phe levels, Tyr levels and Phe/Tyr ratios in BH4 and non BH4 responsive patients. Results: Variations in blood Phe levels were greater in the non-BH4 group (BH4: median 338μmol/L, 95% Confidence Interval (CI) 329–346, mean: 358μmol/L, CI 350–366; non-BH4: median 338μmol/L CI 332–344, mean: 370μmol/L CI 364–376). Variations in blood Tyr levels were slightly greater in the non-BH4 group: (BH4: median 59μmol/L CI 58–61, mean 67 CI 66–69; non-BH4: median 62μmol/L CI 61–63, mean 70 CI 69–71). The variation in Phe/Tyr ratios was greater in the non-BH4 group (mean 6.12, CI 5.9–6.3) than in the BH4 group (Mean 5.44, CI 5.3–5.6), particularly at blood Phe levels >600μmol/L. Conclusion: BH4 responsive patients have smaller variations in blood Phe levels and tighter Phe/Tyr ratios than non-BH4 responsive patients, particularly at high blood Phe levels. If decreased fluctuations in Phe levels and a decreased Phe/Tyr ratio are indeed neuro-protective, then BH4 responsiveness is advantageous over diet alone in PKU. Neuropsychological testing in patients who have been treated with BH4 long term may be able to ascertain the clinical benefit of these biochemical findings. [Copyright &y& Elsevier]