Demographics, diagnosis and treatment of 256 patients with tetrahydrobiopterin deficiency in mainland China: results of a retrospective, multicentre study

Abstract Background National coverage of neonatal screening for hyperphenylalaninaemia (HPA) in China is still low and tests to differentiate causes of HPA are not performed in many centres. This study aimed to describe the demographics, geographic distribution, diagnosis, treatment and clinical outcomes of treatment, including intellectual development, in patients with tetrahydrobiopterin (BH 4 ) deficiency in mainland China. Methods This was a retrospective, multicentre, chart review in patients with BH 4 deficiency across mainland China born 1985–2010. Results Two hundred fifty six patients were included; 59.9 % (267/446) of parents were from eastern China. Median (interquartile range) age at diagnosis decreased from 12.0 (5.5, 102.0) months to 2.0 (1.0, 3.5) months in patients born 1985–1999 ( n = 28) and 2005–2010 ( n = 152), respectively. 6‐Pyruvoyl‐tetrahydropterin synthase (PTPS) deficiency was the primary cause of BH 4 deficiency (96.0 %); four hotspot mutations accounted for 76.6 % of PTS gene mutations; two novel variants in the QDPR gene were identified. Most patients (83.6 %) received treatment with BH 4 , l ‐dopa, 5‐hydroxytryptophan and/or diet therapy. Target blood Phe concentration was confirmed at 88.9 % of visits; median (Q1, Q3) blood Phe concentration was 106.8 (73.0, 120.0) μmol/L during therapy and 117.0 (67.1, 120.0) μmol/L at last visit. Median (Q1, Q3) WISC IQ score was 80.0 (69.0, 90.0) in 33 patients. DQ scores were within normal range (≥85) for 37/59 (62.7 %) patients. Physical development indicators were within normal ranges. Treatment‐related adverse events, reported in 20/256 (7.8 %) patients, were mild‐to‐moderate in severity. Conclusion This study provides valuable information on the current and historical situation of BH 4 deficiency in mainland China.