Screening for neonatal inherited metabolic disorders by tandem mass spectrometry in Guangzhou.

To analyze the screening results for inherited metabolic disorders (IMD) in newborns by tandem mass spectrometry (MS/MS) in Guangzhou.A total of 272 117 newborns in Guangzhou from Jan 2015 to Dec 2020 were screened for IMD by MS/MS in Guangzhou Newborn Screening Center. When the primary screening was positive, the newborns and their mothers were recalled. For those with positive in re-examination, the biochemical and related genetic analysis were required for confirmation. The screening results, clinical characteristics and outcomes of the confirmed cases were retrospectively analyzed and the performance was optimized. Among 272 117 neonates, 1808 (0.66%) cases were positive in primary screening, and 1738 cases (96.13%) were recalled for review. The median clinical diagnosis time was 15 d after birth. A total of 79 cases of IMD were diagnosed, including 23 with aminoacidopathy, 17 with disorder of organic acid metabolism and 39 with fatty acid oxidation disorders, involving 21 diseases. The incidence rate was 1/3444 in newborns, and the positive predictive value of 4.5%. Four false negative cases were found, all of them were citrin deficiency. The common diseases were primary carnitine deficiency (26.6%), methylmalonic aciduria (12.7%) and phenylalanine hydroxylase deficiency (11.4%). The mothers of 32 cases were confirmed, including 30 cases of primary carnitine deficiency, 1 case of isobutyl-coenzyme A dehydrogenase deficiency and 1 case of 3-methylcromaryl coenzyme A carboxylase deficiency. The detection rate was 1/2451 in total population. During the follow-up, most patients remain asymptomatic, except for 5 severe cases who died early (1 case of maple syrup urine disease, 2 cases of isolated methylmalonic acidurmia, and 2 cases of carnitine-acylcarnitine translocase deficiency); and 10 cases of organic acid metabolism disorders developed mild psychomotor developmental retardation. After optimizing the screening indicators, the number of initial screening positives dropped to 903, and the positive predictive value increased to 9.1%, and no confirmed cases were missed. The incidence rate of fatty acid oxidation disorders is high in Guangzhou. A variety of IMD can be effectively screened out by MS/MS, and the screening performance can be improved by optimizing screening indicators.

Study on the electrodeposition of uranium in chloride molten salt.

This study focuses on the recovery of UO2 from oxide spent fuel using electrodeposition. U3O8 was used as the initial material and dissolved in NaCl-2CsCl using NH4Cl at high temperatures by means of chlorination reaction. The electrolysis process was conducted using a three-electrode system to investigate the effects of cathode material and diameter, electrolysis temperature, electrolysis time, electrolysis voltage, and uranium concentration in the molten salt on the electrolysis reaction. By optimizing the electrolysis conditions, pure UO2 with a recovery efficiency of 97% was obtained, and the products were characterized using XRD, SEM-EDS, ICP-AES and XPS. It was found that within the scope of this experiment, increasing the cathode diameter, extending the electrolysis time, and increasing the reduction voltage appropriately all led to an improvement in the recovery efficiency of the electrolysis reaction, while other conditions had minimal effect on the reaction. Furthermore, doping of the electrolyte system was performed by adding La, Ce and Nd elements, while the removal of La showed good purification effects, with a maximum decontamination factor of 119. Furthermore, the system showed good purification effects for Nd, with a decontamination factor of 57.

Same-sex twins have a high incidence of congenital hypothyroidism and a high probability to be missed at newborn screening.

BACKGROUND: We estimated the incidence of CH in twins, analyse the clinical features of CH cases in twins and further evaluate the CH screening strategy and recall procedures for twins. METHODS: A retrospective investigation of the screening results and confirmed cases in 724,791 newborns was conducted from 2015 to 2017 in Guangzhou. Clinical features were compared between twins with CH and singletons with CH. In addition, the twins were further divided into same-sex twins and different-sex twins to analyse the characteristics and incidence of CH and to compare differences in the confirmed cases in the 2 groups. RESULTS: The incidence of CH in same-sex twins was 1/593, which was much higher than the incidence of CH in singletons (1/1323) and different-sex twins (1/3060). Of the 20 twins diagnosed with CH, 17 were same-sex twins and 3 were different-sex twins. Among the six pairs of same-sex twins with CH, four had TSH inconsistency, which reached 67%. Eight of the 17 cases of same-sex twins diagnosed with CH had negative results at the first screening. CONCLUSIONS: Distinguishing same-sex twins from different-sex twins during newborn screening is more feasible. The incidence of CH in same-sex twins is much higher than that in the general population and the risk of transient CH is relatively high. In positive cases in same-sex twins, the simultaneous recall of the twin can effectively avoid a missed diagnosis. The screening center should properly evaluate the recall strategy and screening procedure for twins, especially twins of the same-sex.

Identification of an inherited pathogenic DNAJC12 variant in a patient with hyperphenylalalinemia.

Hyperphenylalaninemia (HPA), an abnormal condition of phenylalanine metabolism, was recently reported to be caused by DNAJC12 mutations. As the heat shock co-chaperone, DNAJC12 prevents the aggregation of misfolded or aggregation-prone proteins and maintain the correct assembly and degradation. Here, we report a patient with unexplained HPA detected by newborn screening. Differential diagnoses of pterin profile and targeted next generation sequencing of excluded the most common causes of the defects of the enzyme phenylalanine hydroxylase or its cofactor tetrahydrobiopterin (BH4). Sanger sequencing revealed a novel homozygous deletion variant of c.262del in DNAJC12, which was predicted to produce the truncated protein (p.Q88SfsTer6) and was considered pathogenic to result in the symptoms of global developmental delays clinically. Treatment with the combination of BH4, the neurotransmitter precursors of dopamine and serotonin, and phenylalanine-restricted diet enabled the patient to improve his development and stabilize his phenylalanine level in a reasonable range. These findings expanded the spectrum of the DNAJC12 mutations and provided new insights on patient management, further supporting the causal relationships of DNAJC12 and HPA.