Analysis of types and metabolic profiles of hyperphenylalaninemia

Objective To study the characteristics of hyperphenylalaninemia (HPA) and the differences in blood and urine metabolic index and their correlation. Methods A total of 137 patients with HPA diagnosed by the Pediatric Inherit Metabolism and Endocrine Department, Guangdong Women and Children′s Hospital, Guangzhou Medical University from January 2014 to June 2017, were enrolled.Tandem mass spectrometry (MS/MS), gas chromatography/mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) were used to analyze the concentration of blood and urine metabolites in children, and the patients were divided into different groups according to the drug load test of tetrahydrobiopterin (BH4) and dihydrobiopterindine reductase (DHPR) deficiency.The HPA metabolite analysis of horizontal concentration by statistical differences and correlation analysis were performed. Results Among the 137 cases of HPA, there were 101 cases (73.7%) of phenylalanine hydroxylase deficiency (PAH), and among them 21 cases (15.3%) were classic phenylketonuria (PKU), 37 cases were mild PKU (27.0%), 43 cases (31.4%) were mild HPA.There were 22 cases (16.1%) with BH4 reaction, and 79 cases (57.7%) of non-reactive type.Besides, there were 36 cases(26.3%) of tetrahydrobiopterin deficiency (BH4D), of which 6-pyruvoyl tetrahydropterin synthase deficiency(PTPS) in 34 cases(24.8%) and dihydrobiopterindine reductase deficiency (DHPR) in 2 cases (1.5%). Urinary phenylacetic acid (r=0.673, P 0.05). Conclusions Through the analysis of the different types of HPA metabolic profiles, it can help to master the incidence and characteristics in the region, within a certain concentration range of blood Phe, the phenylacetic acid, phenyllactic acid, phenylpyruvic acid should not be tested by GC-MS alone.Uterine erythropoietin analysis of BH4D classification and identification of BH4 reaction, non-reactive PKU have a supporting role, so master the metabolic index of various types of concentration and relevance of HPA, it can provide basis for early diagnosis, accurate treatment and follow-up. Key words: Hyperphenylalaninemia; Metabolic profiling; Phenylalanine hydroxylase deficiency; Tetrahydrobiopterin deficiency