Objective To explore the clinical feature and gene types in patients with primary carnitine deficiency. MethodsClinical data of 6 patients with primary carnitine deficiency and 2 patients with maternal carnitine deficiency found in the screening by tandem mass spectrometry technology during December 2013 to December 2016 were retrospectively analyzed. Results The free carnitine levels of 8 patients in initial and recall screening were 5.85±1.65 μmol/L and 5.22±1.02 μmol/L. Two pathogenic alleles were detected in each patient with primary carnitine deficiency by genetic and metabolic disease panel based on Ion Torrent semiconductor sequencing. After treatment with oral L-carnitine, the free carnitine levels of 6 patients with primary carnitine deficiency were 20.24±3.88 μmol/L. The carnitine levels returned to normal after mixed feeding for one week in 2 patients with maternal carnitine deficiency, and no genetic diagnosis was carried out. Conclusion Primary carnitine deficiency can be effectively detected using tandem mass spectrometry technology and next generation sequencing panel and the prognosis is good with early standard treatment.

Objective:To investigate the clinical characteristics and pathogenic mutations of propionic acidemia.Methods:Clinical data of two patients with propionic acidemia admitted to the Obstetrics and Gynecology Hospital of Nanjing Medical University from May 2017 to June 2018 were collected. Genomic DNA was extracted from the peripheral blood of the patients and their parents. Inherited disease panel based on Ion Torrent semiconductor sequencing technology was performed to detect gene mutations, and those with suspected pathogenic mutations were verified by Sanger sequencing. Descriptive statistical analysis was used for data analysis.Results:Case 1 was suspected of sepsis and admitted to the Obstetrics and Gynecology Hospital of Nanjing Medical University due to "drowsiness and milk rejection" on the second day after birth. Tandem mass spectrometry suggested the level of propionyl carnitine and its ratios to acetylcarnitine and free carnitine were increased. Urine gas chromatography-mass spectrometry showed elevated 3-hydroxypropionic acid and methylcitric acid. Genetic analysis revealed that the infant carried c.331C>T (p.R111X)/c.1228C>T (p.R410W) compound heterozygous mutations in the PCCB gene. The infant was diagnosed with propionic acidemia and treated with a special diet with an L-Carnitine supplement but died of sudden coma and vomiting without precipitating factors at three months of age. Case 2 presented with sudden vomiting, drowsiness, and anergia on the admission at five-months old. Tandem mass spectrometry showed increased propionyl carnitine level and its ratios. Compound heterozygous mutations of c.146delG (p.G49EfsX16)/c.1253C>T (p.A418V) in the PCCB gene were identified in the patient, of which c.146delG (p.G49EfsX16) was a de novo mutation and was evaluated as a pathogenic mutation. The patient was on a special diet with an L-Carnitine supplement, but with disobedience. Followed up to the age of three years and eight months, the child was severely underdeveloped. Conclusions:Neonates with clinically suspected sepsis may have propionic acidemia, and tandem mass spectrometry and genetic testing should be performed as soon as possible to confirm or rule out the diagnosis. Further investigations on the pathogenesis and function of the new mutation are still needed.

OBJECTIVE: To analyze the clinical features and genetic variants in four neonates with very long chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency. METHODS: Neonates with a tetradecenoylcarnitine (C14:1) concentration at above 0.4 μmol/L in newborn screening were recalled for re-testing. Four neonates were diagnosed with VLCAD deficiency by MS-MS and genetic testing, and their clinical features and genotypes were analyzed. RESULTS: All cases had elevated blood C14:1, and the values of first recalls were all lower than the initial test. In 2 cases, the C14:1 had dropped to the normal range. 1 case has remained at above 1 μmol/L after the reduction, and the remainder one case was slightly decreased. In total eight variants of the ADACVL genes were detected among the four neonates, which included 5 missense variants and 3 novel variants (p.Met344Val, p.Ala416Val, c.1077+6T>A). No neonate showed salient clinical manifestations. CONCLUSION Above findings have enriched the spectrum of ADACVL gene mutations and provided a valuable reference for the screening and diagnosis of VLCAD deficiency.
Acyl-CoA Dehydrogenase/genetics* ; Acyl-CoA Dehydrogenase, Long-Chain ; Congenital Bone Marrow Failure Syndromes ; Genetic Testing ; Humans ; Infant, Newborn ; Lipid Metabolism, Inborn Errors ; Mitochondrial Diseases ; Muscular Diseases ; Tandem Mass Spectrometry

OBJECTIVE: To explore the genetic basis for an infant with early-onset argininemia. METHODS: Potential variant was detected with an Ion Torrent semiconductor sequencer using a gene panel for inherited diseases. Suspected variants were verified by Sanger sequencing. RESULTS: Genetic testing indicated that he has carried c.560+2T>C and c.811T>C compound heterozygous variant of the AGR1 gene, which were inherited from his father and mother, respectively. Among these, c.560+2T>C was suspected to be pathogenic, while c.811T>C was of unknown clinical significance, and both were not reported previously. CONCLUSION The c.560+2T>C and c.811T>C compound heterozygous variants of the AGR1 gene probably underlies the argininemia in this child. Above finding has enriched the variant spectrum of the AGR1 gene.
Arginase ; genetics ; Female ; Genetic Testing ; Humans ; Hyperargininemia ; genetics ; Infant ; Male

OBJECTIVE: To analyze the clinical and genetic features of two children suspected for arginylsuccinuria aciduria. METHODS: The patients were subjected to high-throughput sequencing using a gene panel. RESULTS: Both patients had high citrulline (87.37-156.10 μmol/L) measured by mass spectrometry/mass spectrometry (MS/MS) upon neonatal screening but had no symptoms. Two compound heterozygous variants of the ASL gene were detected in patient 1 (exon 6: c.467C>T inherited from her father and exon 7: c.556C>T inherited from her mother), among which c.556C>T is novel. Patient 2 had mental retardation and two full siblings who had died of hyperammonemia. Two compound heterozygosity variants of the ASL gene were detected (exon 3: c.281G>T inherited from his father and intron: c.208-15T>A inherited from his mother). Both were novel mutations. CONCLUSION Variants of the ASL gene probably underlie the argininosuccinic aciduria in the two patients. Above findings have enriched the spectrum of ASL mutations.
Argininosuccinic Aciduria ; Child ; Female ; Genetic Testing ; Humans ; Hyperammonemia ; Infant, Newborn ; Neonatal Screening ; Tandem Mass Spectrometry

Objective:To analyze the detection of neonatal inherited metabolic diseases in Nanjing.Methods:We researched the results of 175 767 newborns by tandem mass spectrometry from December 2013 to July 2018. Amino acids, acylcarnitines, and succinylacetone were detected by non-derivatized tandem mass spectrometry to screen the abnormity of newborn amino acid, organic acid, or fatty acid oxidation metabolism disease. Gene panels based on high throughput sequencing technology were carried out to detect gene mutation of positive neonates. Descriptive statistics were used to analyze all the data.Results:The positive rate of primary screening was 2.1% (3 691/175 767), 3 598 of 3 691 positive cases were recalled. At last, 62 cases of the inherited metabolic disease were diagnosed. Among them, there were 35 cases of amino acid metabolism disease, 12 cases of organic acid metabolism disorder, and 15 cases of fatty acid metabolism defect. The total incidence of neonatal inherited metabolic disease was 0.035 3%, among which amino acid metabolic diseases were 0.019 9%, organic acid metabolic diseases were 0.006 8%, and fatty acid metabolic diseases were 0.008 5%. The diseases with the highest incidence were phenylalanine hydroxylase deficiency (0.015 9%), methylmalonic acidemia (0.005 1%), and primary carnitine deficiency (0.005 1%). Among 62 children, 51 (82.2%) were diagnosed by gene diagnosis (including 17 cases of phenylalanine hydroxylase deficiency and 34 cases of other inherited metabolic diseases). Another 11 children with phenylalanine hydroxylase deficiency refused gene diagnosis. Two pathogenic mutations were found in 17 children with phenylalanine hydroxylase deficiency. Two pathogenic mutations were found in 29 of the other 34 children with inherited metabolic disease, which were from their parents, while only one pathogenic mutation was found in the other five children, of which two cases with hypermethioninemia were autosomal dominant inheritance.Conclusions:Neonatal inherited metabolic diseases with high incidence in Nanjing are phenylalanine hydroxylase deficiency, methylmalonic acidemia, and primary carnitine deficiency. Some cases screened by tandem mass spectrometry only showed abnormal screening indicators. No specific clinical symptoms were found during follow-up, and further follow-up was needed.

Objective: To explore the genetic basis for an infant with early-onset argininemia. Methods: Potential variant was detected with an Ion Torrent semiconductor sequencer using a gene panel for inherited diseases. Suspected variants were verified by Sanger sequencing. Results: Genetic testing indicated that he has carried c. 560+ 2T>C and c. 811T>C compound heterozygous variant of the AGR1 gene, which were inherited from his father and mother, respectively. Among these, c. 560+ 2T>C was suspected to be pathogenic, while c. 811T>C was of unknown clinical significance, and both were not reported previously. Conclusion The c. 560+ 2T>C and c. 811T>C compound heterozygous variants of the AGR1 gene probably underlies the argininemia in this child. Above finding has enriched the variant spectrum of the AGR1 gene.

Objective:To investigate the current situation of diet management in patients with colorectal cancer after stent-based diverting technique, and to provide basis for formulating relevant nursing intervention strategies.Methods:Objective sampling method was used to conduct semi-structured interviews on 15 patients who underwent stent-based diverting technique for colorectal cancer and had the bypass tube removed from Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University from March to July 2023. The interview outline was established based on information-motivation-behavioral skills(IMB) model, and the data were analyzed, summarized and extracted by Colaizzi 7-step analysis method.Results:There were 10 males and 5 females, aged 34-76 years old. According to the three elements of the IMB model, the current situation of diet management was summarized into nine themes. The information included the difficulty in obtaining effective diet guidance information, the lack of specific diet guidance content, the need for individualized diet information guidance mode, and the poor continuity of information exchange after discharge. The motivations included ignoring the importance of diet management, dislike the taste of oral nutritional preparations, and weak support from family members. Behavioral skills include inadequate tube care skills and lack of oral nutrition preparation skills.Conclusions:There are many problems in the diet management of patients after colorectal cancer stent-based diverting technique. Medical staff should optimize the diet education information of colorectal cancer patients after surgery, provide multi-level, multi-time and multi-form continuous care, mobilize the active participation of family members, improve the motivation of patients′ diet management, refine the nursing process of the bypass tube, strengthen the application guidance of oral nutrition preparation skills, and improve patients′ diet management ability.

Objective To investigate the constitutive characteristics and the change trend of gynecologic malignant tumors in hospitalized patients in Guangxi Zhuang Autonomous Region over the recent 20 years.Methods Clinical data of 8009 in-patients who suffered from gynecologic malignant tumors in 23 hospitals from 1985 to 2004 in Guangxi Zhuang Autonomous Region were analyzed,with respect to the tumor types and change trend.Results(1)The leading 4 types of malignant tumors were cervical cancers, ovarian cancers,endometrial cancers,and malignant trophoblastic tumors according to the constitutive ratios of the tumors.The constitutive ratio of cervical cancer patients rose year by year,from 17.48% during the 1985-1989 period to 49.25% during the 2000-2004 period(P0.05).(2)The occurring age of cervical cancers became younger obviously,from≥60 years old dropped to

Objective:To identify the possible pathogenesis of a neonate with carnitine palmitoyltransferase 1A (CPT1A) deficiency by analyzing genetic variants.Methods:Potential variants were detected with an Ion Torrent semiconductor sequencer using a gene panel for inherited diseases, and candidate variants were verified by Sanger sequencing.Results:Genetic testing indicated that the neonate has carried c. 1895T>A(p.Leu632X) and c. 1153G>A(p.Ala385Thr) compound heterozygous variants of the CPT1A gene, which were inherited from his father and mother, respectively. Both variants were verified as novel through the retrieval of HGMD database, ClinVar database and literature. According to the standards and guidelines of the American College of Medical Genetics and Genomics, the c. 1895T>A variant was predicted as pathogenic(PVS1+ PM2+ PP4) and c. 1153G>A as likely pathogenic (PM1+ PM2+ PM3+ PP3). Conclusion:The c. 1895T>A and c. 1153G>A compound heterozygous variants of the CPT1A gene might underlie the pathogenesis in this child. Above results have provided a basis for clinical diagnosis and genetic counseling, and enriched the variant spectrum of the CPT1 deficiency.