ABSTRACT
OBJECTIVE@#To investigate the clinical manifestations, biochemical abnormalities and pathogenic variants among children with Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency detected by neonatal screening.@*METHODS@#A total of 2 730 852 newborns were screened from January 2016 to December 2021 with liquid chromatography tandem mass spectrometry. Suspected SBCAD deficiency patients were diagnosed by urine organic acid analysis and high-throughput gene sequencing analysis. The clinical, biochemical and genetic changes of the confirmed cases were analyzed, in addition with guidance for diet and life management, L-carnitine supplement, and survey of growth and intellectual development.@*RESULTS@#Twelve cases of SBCAD deficiency were diagnosed, which yielded a prevalence of 1/227 571. The lsovaleryl carnitine (C5) of primary screening blood samples was between 0.6 and 2.1 µmol/L, all exceeded the normal range. C5/acety1 carnitine (C2) was between 0.02 and 0.12, with 6 cases exceeding the normal range. C5/propionyl carnitine (C3) was between 0.1 and 1.16, with 5 cases exceeding the normal range. Free carnitine (C0) was between 18.89 and 58.12 µmol, with 1 case exceeding the normal range. Three neonates with abnormal screening results were recommended to have appropriate restriction for protein intake and two were given L-carnitine. During follow-up, their C5 has ranged from 0.22 to 2.32 µmol/L, C5/C2 has ranged from 0.01 to 0.31, C5/C3 has ranged from 0.14 to 1.7. C5 or C5/C2 and C5/C3 were transiently normal in all patients except for case 8 during the neonatal screening and follow-up. C0 was 17.42 ∼ 76.83 µmol/L Urine organic acid analysis was carried out in 9 of the 12 cases, and 2-methylbutyroglycine was elevated in 8 cases. Urine organic acid analysis was carried out in 9 cases, and 2-methylbutyrylglycine was increased in 8 cases. Genetic analysis was carried out for 11 children, and in total 6 ACADSB gene variants were identified, which included 4 missense variants (c.655G>A, c.923G>A, c.461G>A, c.1165A>G), 1 frameshift variant (c.746del) and 1 nonsense variant (c.275C>G). Among these, the C.461G>A variant was unreported previously. The most common variants were c.1165A>G (40.9%) and C.275C>G (22.7%). The patients were followed up for 18 days to 55 months. Only one patient had mental retardation, with the remainders having normal physical and mental development.@*CONCLUSION@#SBCAD deficiency is a rare disease. The detection rate of newborn screening in this study was 1/227 571. Early intervention can be attained in most asymptomatic patients through neonatal screening. In this study, the common gene variants are c.1165A>G and c.275C>G.
Subject(s)
Humans , Infant, Newborn , Amino Acid Metabolism, Inborn Errors/genetics , Carnitine , Neonatal Screening/methodsABSTRACT
Objective To assess the feasibility of the log file-based three-dimensional independent dose verification system for the quality assurance of clinical radiotherapy.Methods The statistical values of the percentage depth dose,off-axis curves and output factor calculated by the Mobius system were statistically compared with the measured data by three-dimensional water tank.The three-dimensional independent dose verification in clinical radiotherapy plan and the acceleratr log file-based three-dimensional dose verification during the treatment were performed in 17 patients with nasopharyngeal cancer.The accuracy of dose calculation and reconstruction of Mobius system was assessed.A statistical analysis was performed on the intra-fractionalγpass rate (3％/3 mm) for each patient to evaluate the stability of intra-fractional radiotherapy.Results The percentage depth dose,off-axis curve and output factor statistically calculated by the Mobius system matched well with the data measured by three-dimensional water tank.The dose-volume histogram (DVH) parameters between the target area and organ at risk during clinical radiotherapy plan were statistically compared in 17 patients with nasopharyngeal cancer.The maximum deviation was-2.16％ for the three-dimensional independent dose verification in the clinical radiotherapy plan,and 0.18 Gy for the accelerator log file-based three-dimensional dose verification.The averageγpass rate for 17 nasopharyngeal cancer patients was 99.26％,and the maximum deviation of intra-fractional radiotherapy was below 0.5％.Conclusions The function of dose reconstruction and independent calculation of the Mobius system yeilds the same accuracy with the treatment planning system,which can quickly perform three-dimensional independent dose verification in the clinical radiotherapy plan and accelerator log file-based three-dimensional dose verification throughout the treatment,thereby guarantting and providing the safe and reliable technical support for clinical treatment.