Objective: To determine the incidence and mutational types of fatty acid oxidation disorders (FAOD) in central-northern region of Guangxi. Methods: A total of 62 953 neonates were screened for FAOD during December 2012 and December 2017. Acyl-carnitine profiling of neonatal blood sample was performed by tandem mass spectrometry using dry blood spots on a filter paper. The diagnosis of FAOD was confirmed by organic acid profiling of urea and genetic testing. Results: Eighteen cases of FAOD were diagnosed among the 62 953 neonates. Among these, primary carnitine deficiency (PCD) was the most common type (n=13), which was followed by short-chain acyl-CoA dehydrogenase deficiency (SCADD) (n=2), medium- chain acyl-CoA dehydrogenase deficiency (MCADD) (n=1), multiple acyl-CoA dehydrogenase deficiency (MADD) (n=1), and carnitine palmitoyltransferaseⅡdeficiency (CPT ⅡD) (n=1). Genetic testing has revealed two previously unreported variants, i. e., c. 337G>A (p.Gly113Arg) of ACADS gene and c. 737G>T (p.Gly246Val) of ETFA gene. Conclusion PCD is the most common FAOD in central-northern Guangxi. Tandem mass spectrometry combined with genetic testing may facilitate early diagnosis of FAOD.

Objective: To screen for potential variants of GCDH gene in 3 patients clinically diagnosed as glutaric aciduria type Ⅰ. Methods: GCDH gene variants was detected by Sanger sequencing among the three children and their family members. Results: Sanger sequencing showed that patient 1 carried compound heterozygosity variants of c. 532G>A (p.Gly178Arg) and c. 655G>A (p.Ala219Thr) of the GCDH gene, while his father and mother respectively carried heterozygous c. 532G>A(p.Gly178Arg) and c. 655G>A (p.Ala219Thr) variants. Patient 2 carried c. 532G>A (p.Gly178Arg) and a novel c. 1060G>T (p.Gly354Cys) compound heterozygous variant, while his father and mother respectively carried heterozygous c. 532G>A (p.Gly178Arg) and c. 1060G>T (p.Gly354Cys) variant. Patient 3 carried homozygous c. 532G>A (p.Gly178Arg) variant of the GCDH gene, for which both of his parents were heterozygous carriers. Conclusion The GCDH gene variant probably underlie the glutaric aciduria type Ⅰ among the 3 patients. Identifcation of the novel variant has enriched the spectrum of GCDH gene variants.

OBJECTIVE: To screen for potential variants of GCDH gene in 3 patients clinically diagnosed as glutaric aciduria type Ⅰ. METHODS: GCDH gene variants was detected by Sanger sequencing among the three children and their family members. RESULTS: Sanger sequencing showed that patient 1 carried compound heterozygosity variants of c.532G>A (p.Gly178Arg) and c.655G>A (p.Ala219Thr) of the GCDH gene, while his father and mother respectively carried heterozygous c.532G>A(p.Gly178Arg) and c.655G>A (p.Ala219Thr) variants. Patient 2 carried c.532G>A (p.Gly178Arg) and a novel c.1060G>T (p.Gly354Cys) compound heterozygous variant, while his father and mother respectively carried heterozygous c.532G>A (p.Gly178Arg) and c.1060G>T (p.Gly354Cys) variant. Patient 3 carried homozygous c.532G>A (p.Gly178Arg) variant of the GCDH gene, for which both of his parents were heterozygous carriers. CONCLUSION The GCDH gene variant probably underlie the glutaric aciduria type Ⅰ among the 3 patients. Identifcation of the novel variant has enriched the spectrum of GCDH gene variants.
Amino Acid Metabolism, Inborn Errors ; genetics ; Brain Diseases, Metabolic ; genetics ; Female ; Glutaryl-CoA Dehydrogenase ; deficiency ; genetics ; Heterozygote ; Humans ; Male

Objective:To analyze assessment value of the hemodynamics of posterior cerebral artery(PCA)detected by transcranial color-coded Doppler(TCCD)ultrasound for occurring cerebral infarction in patients with fetal-type posterior cerebral artery(FTP).Methods:A total of 300 patients with suspected cerebrovascular disease admitted to the Department of Neurology of The Second Hospital of Harbin City from January,2020 to December 31,2023 were retrospectively selected.In these patients,7 cases with cerebral hemorrhage(without complication of cerebral infarction)did not be included.According to the clinical manifestations and the results of imaging examination,293 patients were divided into transient ischemic attack(TIA)group(176 cases)and acute ischemic stroke(AIS)group(117 cases).The differences in FTP detection between TCCD examination and magnetic resonance angiography(MRA)were compared.The differences in PCA hemodynamics among TIA,anterior circulation infarction,posterior circulation infarction and lacunar infarction were compared.The proportions of patients with TIA,anterior circulation infarction,posterior circulation infarction and lacunar infarction combined with FTP were also compared,and the PCA hemodynamics of patients with posterior circulation infarction of bilateral cFTP,unilateral cFTP,bilateral pFTP,unilateral pFTP and nFTP were compared.The proportions of patients with transient ischemic attack(TIA)who occurring AIS at bilateral cFTP,unilateral cFTP,bilateral pFTP,unilateral pFTP and nFTP in short term were compared.The receiver operating characteristic(ROC)curve and area under curve(AUC)were used to assess the predictive value of abnormal PCA hemodynamics of TIA patients,who combined with and/or without FTP,occurred AIS in short term.Results:MRA revealed that a total of 89 patients combined with FTP in 293 patients,of which 14 cases were bilateral cFTP(accounting for 15.73%),and 25 cases were unilateral cFTP(accounting for 28.09%),and 8 cases were bilateral pFTP(accounting for 8.99%),and 42 cases were unilateral pFTP(accounting for 4 7.19%).According to TCCD testing,it was found that a total of 89 cases combined with FTP in 293 patients,of which 16 cases were bilateral cFTP(accounting for 17.98%),and 23 cases were unilateral cFTP(accounting for 25.84%),and 8 cases were bilateral pFTP(accounting for 8.99%),and 42 cases were unilateral pFTP(accounting for 47.19%).There was favorable consistency between TCCD and MRA(Kappa=0.899).Under TCCD,the blood flow velocity(Vp)and resistance index(RI)of systolic stage of PCA in patients with posterior circulation infarction were significantly higher than those in patients with TIA,anterior circulation infarction,and lacunar cerebral infarction(F=15.392,9.032,P<0.05),respectively.Patients with posterior circulation infarction were more likely to occur bilateral cFTP.The Vp,Vm and Vd of patients with bilateral cFTP were significantly higher than those of patients with bilateral pFTP,unilateral pFTP and non-FTP(F=14.932,8.884,6.054,P<0.05),respectively.The proportion of occurring AIS in TIA patients with bilateral cFTP was significantly higher than that in TIA patients with unilateral cFTP,bilateral pFTP,unilateral pFTP and nFTP(Z=6.883,7.568,6.253,6.772,P<0.05),and the proportions of occurring AIS in TIA patients with unilateral cFTP,bilateral pFTP and unilateral pFTP were significantly higher than that in TIA patients with nFTP(Z=5.986,6.877,6.856,P<0.05),respectively.A total of 45 cases(accounting for 25.57%)of 176 TIA patients occurred AAIS within 3 months after they discharged.The AUC value of predictive value of Vp for occurring AIS in 45 TIA patients with FTP was 0.818,which was significantly higher than that(AUC=0.589)for occurring AIS in 131 TIA patients with non-FTP.Conclusion:Patients with posterior circulation cerebral infarction are prone to occur PCA hemodynamic abnormalities.In patients with posterior circulation infarction,the PCA blood flow velocity in patients with bilateral cFTP significantly accelerates.PCA hemodynamic ultrasound examination has a certain of predictive value for occurring AIS in short term in TIA patients who combine with FTP.

OBJECTIVE: To carry out mutation analysis and prenatal diagnosis for a family affected with primary carnitine deficiency. METHODS: Genomic DNA of the proband was extracted from peripheral blood sample 10 days after birth. The 10 exons and intron/exon boundaries of the SLC22A5 gene were subjected to PCR amplification and Sanger sequencing. The proband's mother was pregnant again two years after his birth. Fetal DNA was extracted from amniocytes and subjected to PCR and Sanger sequencing. RESULTS: Tandem mass spectrometric analysis of the proband revealed low level of plasma-free carnitine whilst organic acids in urine was normal. Compound heterozygous SLC22A5 mutations c.1195C>T (inherited from his father) and c.517delC (inherited from his mother) were detected in the proband. Prenatal diagnosis has detected no mutation in the fetus. The plasma-free carnitine was normal after birth. CONCLUSION Appropriate genetic testing and prenatal diagnosis can prevent further child with carnitine deficiency. The identification of c.517delC, a novel mutation, enriched the spectrum of SLC22A5 mutations.
Cardiomyopathies ; genetics ; Carnitine ; deficiency ; genetics ; Child, Preschool ; DNA Mutational Analysis ; Female ; Humans ; Hyperammonemia ; genetics ; Muscular Diseases ; genetics ; Mutation ; Pregnancy ; Prenatal Diagnosis ; Solute Carrier Family 22 Member 5 ; genetics

Objective:To compare the effects of thoracoscopic anatomical segmentectomy and thoracoscopic lobectomy on patients' respiratory function.Methods:Retrospective analysis of 326 patients who underwent thoracoscopic surgery from July 2016 to July 2019(209 patients underwent anatomical segmentectomy, 117 patients underwent lobectomy). According to variables including gender, age, tumor location, smoking history and BMI, two propensity score-matched cohorts including 89 patients respectively were constructed. The patients’ baseline data and respiratory function date of the patients pre-operation and post-operation were analyzed. The measurement data that obey the normal distribution were described by mean±standard deviation, and the t-test was used for comparison between groups; the measurement data of non-normal distribution was described by the median value( P25, P75), and the Wilcoxon rank sum test was used for the comparison between groups; The data was described by frequency, and the chi-square test or Fisher's exact probability method was used for comparison between groups. Results:At the first-month follow-up after surgery, there was no significant difference in the variation of FVC[(0.48±0.40)L vs.(0.34±0.37)L, P=0.215)and FEV1[(0.52±0.46)L vs.(0.43±0.77)L, P=0.364), and in the change rate of FVC(%)[15.23(8.74, 21.25) vs. 14.58(7.75, 19.40), P=0.122], FEV1(%)[17.25(9.56, 22.78) vs. 16.42(9.15, 20.28), P=0.154]and DLCO(%)[18.54(10.88, 25.68)vs. 17.45(9.58, 23.75) P=0.245]. Between the segmentectomy group and lobectomy group, there was a significant difference in the alteration of FVC[(0.50±0.47)L vs. (0.29±0.31)L, P=0.031] and FEV1[(0.44±0.34)L vs.(0.24±0.23)L, P<0.001], the change rate of FVC(%)[14.27(7.87, 22.32) vs. 9.95(5.56, 17.24), P=0.008]、FEV1(%)[15.23(8.36, 22.17)vs. 10.05(5.15, 18.54), P<0.001]and DLCO(%)[13.74(6.24, 19.78) vs. 4.45(-2.32, 13.75), P=0.023]in the 6th month after surgery. The lobectomy group had a higher variation of FEV1[(0.34±0.49)L vs.(0.18±0.26)L, P=0.006] and change rate of FVC(%)[9.28(2.15, 18.94) vs. 5.24(0.52, 11.45), P=0.0032] and FEV1(%)[10.45(3.15, 21.32) vs. 6.50(1.55, 14.24), P<0.001] in the first year after surgery. However, the variation of FVC[(0.29±0.36)L vs.(0.21±0.24)L, P=0.176) and the change rate of DLCO(%)[8.35(2.15, 16.45) vs. 6.23(2.12, 14.54), P=0.143] didn't show a significant difference between the two groups. Conclusion:Whether in the short or the middle postoperative period, segmentectomy can preserve postoperative respiratory function than lobectomy.

OBJECTIVE: To detect variants of IVD gene among 4 neonates with suspected isovalerate acidemia in order to provide a guidance for clinical treatment. METHODS: 111 986 newborns and 7461 hospitalized children with suspected metabolic disorders were screened for acyl carnitine by tandem mass spectrometry. Those showing a significant increase in serum isovaleryl carnitine (C5) were analyzed for urinary organic acid and variants of the IVD gene. RESULTS: Four cases of isovalerate acidemia were detected, which included 2 asymptomatic newborns (0.018‰, 2/111 986) and 2 children suspected for metabolic genetic diseases (0.268‰, 2/7461). The formers had no obvious clinical symptoms. Analysis of acyl carnitine has suggested a significant increase in C5, and urinary organic acid analysis has shown an increase in isovaleryl glycine and 3-hydroxyisovalerate. Laboratory tests of the two hospitalized children revealed high blood ammonia, hyperglycemia, decreased red blood cells, white blood cells, platelets and metabolic acidosis. The main clinical manifestations have included sweaty foot-like odor, feeding difficulty, confusion, drowsiness, and coma. Eight variants (5 types) were detected, which included c.158G>A (p.Arg53His), c.214G>A (p.Asp72Asn), c.548C>T (p.Ala183Val), c.757A>G (p.Thr253Ala) and 1208A>G (p.Tyr403Cys). Among these, c.548C>T and c.757A>G were unreported previously. None of the variants was detected by next generation sequencing of 2095 healthy newborns, and all variants were predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION The incidence of isovalerate acidemia in Liuzhou area is quite high. Screening of metabolic genetic diseases is therefore recommended for newborns with abnormal metabolism. The discovery of novel variants has enriched the mutational spectrum of the IVD gene.
Infant, Newborn ; Child ; Humans ; Acidosis ; Carnitine ; Erythrocytes ; High-Throughput Nucleotide Sequencing

Objective    To assess the correlation of WHO pathological classification and Masaoka stage of thymomas with its prognosis. Methods    A total of 468 patients with thymomas who received surgeries during 2009-2019 in Huashan Hospital, Fudan University, were collected. There were 234 males and 234 females with an average age of 21-83 (49.6±18.7) years. A total of 132 patients underwent video-assisted thoracic surgery (VATS) and 336 patients underwent thymectomy with median sternal incision. The follow-up time was 5.7±2.8 years. The clinical data of the patients were analyzed. Results    The amount of intraoperative bleeding was 178.3±133.5 mL in the median sternal incision group, and 164.8±184.1 mL in the VATS group (P=0.537). The operative time was 3.3±0.7 h in the median sternal incision group and 3.4±1.2 h in the VATS group (P=0.376). Postoperative active bleeding, phrenic nerve injury and chylothorax complications occurred in 8 patients, 9 patients and 1 patient in the VATS group, respectively, and 37 patients, 31 patients and 7 patients in the median sternal incision group, respectively. There was no statistical difference between the two groups (P=0.102, 0.402, 0.320). The 5-year cumulative progression free survival (PFS) rates of patients with WHO type A, AB, B1, B2, B3 and C thymomas were 100.0%, 100.0%, 95.7%, 81.4%, 67.5% and 50.0%, respectively (P<0.001). The 5-year PFS rates of patients with Masaoka stageⅠ-Ⅳ thymomas were 96.1%, 89.2%, 68.6% and 19.3%,  respectively (P<0.001). The 5-year PFS rate was 87.3% in patients with myasthenia gravis (MG) and 78.2% in patients without MG (P<0.001). The 5-year PFS rates of patients with different surgeries were 82.4% and 83.8%, respectively (P=0.904). Conclusion    WHO pathological classification and Masaoka stage have significant clinical prognosis suggestive effect. Thymoma patients combined with MG have better prognosis, which suggests early diagnosis and treatment of thymoma are important.