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Objective:To analyze the disease spectrum of lysosomal storage disorders(LSDs) and explore the prevalent distributions of different LSD types in one center in Shanghai.Methods:A retrospective analysis was made.A total of 5 476 suspected LSD patients, including 3 415 males and 2 061 females, with a median age of 4 years(1 day to 72 years), were collected from Xinhua Hospital, Shanghai Jiaotong University School of Medicine from August 2008 to May 2022.The activity of different lysosomal enzymes was detected by fluorescent and biochemical methods.Results:A total of 1 520 patients were diagnosed with LSDs, including 972 males and 548 females, with a median age of 4 years(1 day to 59 years), involving 19 different subtypes.Mucopolysaccharidosis(MPS) was the most common type among LSDs, with a frequency of 45.46%(691/1 520), followed by sphingolipidoses [33.88%(515/1 520)] and glycogen storage disease type Ⅱ [16.05%(244/1 520)] successively.MPS Ⅱ was the most common type in MPS, with a frequency of 45.73%(316/691), followed by MPS ⅣA [22.87%(158/691)]. Niemann-Pick A/B, Gaucher, and Krabbe diseases were common in Sphingolipidoses patients, with frequencies of 37.09%(191/515), 34.37%(177/515), and 10.29%(53/515), respectively.Conclusions:LSDs are common genetic metabolic diseases, especially MPS and sphingolipidoses.Newborn screening for LSDs should be carried out timely so that the patients can be treated early and their prognosis can be improved.
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OBJECTIVE To establish the methods to identify the chemical components of Ixeris chinensis， and determine the contents of 7 components （chlorogenic acid， luteolin， quercetin， rutin， protocatechuic acid， isochlorogenic acid A， luteoloside）. METHODS HPLC-Q-Exactive-MS was used to identify the chemical components of I. chinensis. The contents of 7 components in I. chinensis， including chlorogenic acid， were determined by HPLC-MS/MS. RESULTS A total of 45 components were identified in I. chinensis， including 20 organic acids， 13 flavonoids， 4 fatty acids， 4 amino acids， 3 nucleosides， and 1 coumarin. The linear range of chlorogenic acid， luteolin， quercetin， rutin， protocatechuic acid， isochlorogenic acid A and luteoloside were 503.00- 25 150.00， 42.00-2 100.00， 5.05-252.50， 20.05-1 002.50， 25.10-1 255.00， 750.00-37 500.00， 196.00-9 800.00 ng/mL （r≥0.999 2）， respectively. RSDs of precision， stability and reproducibility tests were all less than 3.00% （n＝6）， and average recovery ranged from 96.72% to 105.84% （all RSD＜4.00%， n＝6）. The contents of 7 components in 3 batches of I. chinensis were 1 145.77- 3 261.25， 23.75-97.90， 0.92-2.12， 1.06-23.18， 9.35-21.85， 833.25-1 045.58， 199.56-1 869.78 μg/g， respectively. CONCLUSIONS The established methods for identification and content determination are rapid and simple， and can be used for the identification of chemical components and the content determination of 7 components in I. chinensis.
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OBJECTIVE@#To explore the long-term efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with Mucopolysaccharidosis (MPS), which has rarely been reported in China.@*METHODS@#A 18-month-old boy and a 23-month-old girl undergoing alloHSCT for MPS VI and MPS IH Shanghai Children's Medical Center on March 30, 2006 and September 6, 2006 were selected as the study subjects. A busulfan-based myeloablative regimen was used as the conditioning regimen. Peripheral stem cells were respectively collected from a human leucocyte antigen (HLA) matched sibling carrier donor and a HLA 9/10 matched unrelated donor. Both patients were followed up for more than 15 years. The functions of internal organs before and after the transplantation were compared, and child 1 was also compared with his untreated brother and healthy brother.@*RESULTS@#Both children have achieved full donor chimerism after the transplantation, and their enzymatic activities have remained stable. The enzymatic activity of the child 1 was slightly lower than normal but similar to that of his carrier donor, whilst that of the child 2 was normal. Both children have attended schools with good academic performance. Compared with his untreated brother, the respiratory function and hearing of child 1 have significantly improved. However, his orthopedic and cardiac disorders have still remained and required medical intervention. For child 2, her obstructive pulmonary disease was resolved and cognitive development was well preserved after the HSCT. Her heart disease has become stabilized and even improved with time, though her corneal clouding and skeletal malformation still required surgery.@*CONCLUSION@#MPS patients can sustain long-term and stable enzymatic activities after successful alloHSCT. Compared with untreated patients, their health can be significantly improved, along with considerably prolonged survival, though the long-term efficacy of HSCT for different organs may vary to a certain extent.
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Humans , Child , Male , Female , Infant , Child, Preschool , Graft vs Host Disease/etiology , China , Hematopoietic Stem Cell Transplantation/adverse effects , Mucopolysaccharidoses/etiology , Busulfan , Treatment OutcomeABSTRACT
OBJECTIVE@#To explore the disease spectrum for abnormal 3-hydroxyisovalerylcarnitine (C5OH) metabolism identified through newborn screening and clinical diagnosis patients and the key points for differential diagnosis so as to raise the awareness of pediatricians for such diseases.@*METHODS@#Clinical data of 85 neonates with abnormal C5OH metabolism identified from February 2004 to January 2022 at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were collected. Their clinical manifestations and results of tandem mass spectrometry (MS/MS), gas chromatography mass spectrometry (GC-MS) and genetic testing were retrospectively analyzed.@*RESULTS@#Among the 85 cases, 46 (54.1%) were identified by neonate screening, whilst 39 (45.9%) were clinically diagnosed patients. Five diseases were diagnosed, including 28 cases with multiple carboxylase deficiency (MCD, 32.9%), 29 cases with 3-methylcrotonyl-coenzymeAcarboxylasedeficiency (MCCD, 34.1%), 4 cases with 3-methylglutaconic acid (3-MGA, 4.7%), 7 cases with 3-hydroxy-3-methylglutaric acid (3-HMG, 8.2%), and 17 cases with beta-ketothiolase deficiency (BKD, 20.0%). The disorders were characterized by sudden onset, anorexia, vomiting, diarrhea, abnormal breathing, consciousness disorder, spasm and developmental delay.@*CONCLUSION@#Among newborns with abnormal C5OH metabolism, MCCD is the most common disorder, which was followed by BKD and MCD. For patients with abnormal C5OH metabolism, MCD is the most common, followed by BKD and 3-HMG. C5OH related diseases have great heterogeneity. Combination of blood acylcarnitine levels, urinary organic acid levels and genetic testing based on clinical characteristics can help to attain the diagnosis.
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Humans , Infant, Newborn , China , Neonatal Screening , Retrospective Studies , Tandem Mass Spectrometry/methodsABSTRACT
OBJECTIVE To establish the HPLC fingerprint of Mongolian medicine Sanzisan ，and to evaluate its internal quality by chemical pattern recognition technique comprehensively. METHODS HPLC method was used. Using geniposide as reference，HPLC fingerprints of 15 batches of Sanzisan were drawn with Similarity Evaluation System of TCM Chromatogram Fingerprint（2012 edition）. Similarity evaluation and common peaks identification were conducted. Combined with cluster analysis （CA），principal component analysis （PCA），and orthogonal partial least squares-discriminant analysis （OPLS-DA），the quality of 15 batches of Sanzisan was evaluated ，and the differential markers that affected its quality were screened. RESULTS There were 29 common peaks in 15 batches of Sanzisan ，and the similarity was no less than 0.952，indicating that the chemical composition of the 15 batches of Sanzisan had good consistency. A total of 13 common peaks were identified ，which were chebulic acid ，gallic acid，punicalin，punicalagin A ，punicalagin B ，jasminoside B ，caffeic acid ，corilagin，geniposide，chebulagic acid ，1，2，3，4，6- O-galloylglucose，chebulinic acid ，ellagic acid. Both CA and PCA could divide 15 batches of Sanzisan into four categories ，and the classification results were consistent ，indicating that the quality of 15 batches of Sanzisan had certain differences. Fourteen differential markers （chebulic acid ，gallic acid ，ellagic acid ，etc）that lead to the quality difference between batches were screened out by OPLS-DA. CONCLUSIONS Established HPLC fingerprint analysis method is simple and stable. Combined with chemical pattern recognition analysis ，it can be used for the quality control of Sanzisan.
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OBJECTIVE To establi sh the method for the con tent determination of 11 components in Terminalia chebula from different origins ，and to provide reference for their quality evaluation and superior provenance screening. METHODS Taking 16 batches of T. chebula from different origins as test samples ，high performance liquid chromatography tandem triple quadrupole mass spectrometry was established to determine the contents of 11 components，such as vitexin ，gallic acid ，methyl gallate ，ethyl gallate，ellagic acid ，corilagin，shikimic acid ，ferulic acid ，luteolin，quercetin and rutin. The determination was performed on Shim-pack GIST-HP C 18 column with mobile phase consisted of 0.1％ formic acid solution-methanol at the flow rate of 0.25 mL/ min（gradient elution ）. The sample size was 3 μL，and the column temperature was 35 ℃. Electrospray ionization source was used in positive and negative ion mode ，with multiple reaction monitoring. The atomized gas flow rate was 3 L/min，the heating gas flow rate was 10 L/min，the interface temperature was 300 ℃，the desolvent temperature was 526 ℃，and the heating block temperature was 400 ℃ . Grey correlation analysis （GRA）and technique for order preference by similarity to ideal solution （TOPSIS）methods were used to compare ，analyze and comprehensively evaluate T. chebula from different origins. RESULTS The results of content determination methodology met the relevant requirements. The contents of 11 components in 16 batches of T. chebula were 7.27-106.38，5 370.24-31 010.43，21.42-1 097.50，4.26-111.09，17 940.42-38 490.18，6 247.26-40 182.18，12 125.94- 209 519.96，2.71-9.04，0.24-44.12，1.49-9.17 and 25.35-126.51 μg/g，respectively. The results of GRA and TOPSIS analysis showed that the comprehensive qualities of sample H 12（from Yunnan ），H11（from Guangxi ），H5（from Hunan ），H14（from Guangdong），H13（from Sichuan ），H8（from Guangdong ），H1（from Yunnan ）were better. CONCLUSIONS The established method is fast ，sensitive and reliable ，and can be suitable for comprehensive evaluation of the internal quality and superior provenance screening of T. chebula .
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Acute liver failure (ALF) in children has complex etiologies, among which inherited metabolic diseases account for a high proportion, especially in infants and young children. Inherited metabolic diseases are a group of congenital diseases with destruction of cell physiological function caused by metabolism-related gene mutations, with various types and diverse clinical manifestations. ALF is one of the serious complications caused by such diseases and is easily neglected due to a lack of specific manifestations. ALF caused by such etiologies should be identified as early as possible to reverse the progression of ALF and improve the prognosis of patients. This article summarizes the common inherited metabolic diseases that can cause ALF in children, in order to improve the awareness of such etiology among physicians.
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Influenza pandemic poses public health threats annually for lacking vaccine which provides cross-protection against novel and emerging influenza viruses. Combining conserved antigens inducing cross-protective antibody response with epitopes activating cross-protective cytotoxic T-cells would offer an attractive strategy for developing universal vaccine. In this study, we constructed a recombinant protein NMHC consisting of influenza viral conserved epitopes and superantigen fragment. NMHC promoted the mature of bone marrow-derived dendritic cells and induced CD4+ T cells to differentiate into Th1, Th2 and Th17 subtypes. Mice vaccinated with NMHC produced high level of immunoglobulins which cross-bound to HA fragments from six influenza virus subtypes with high antibody titers. Anti-NMHC serum showed potent hemagglutinin inhibition effects to highly divergent group 1 (H1 subtypes) and group 2 (H3 subtype) influenza virus strains. And purified anti-NMHC antibodies could bind to multiple HAs with high affinities. NMHC vaccination effectively protected the mice from infection and lung damage challenged by two subtypes of H1N1 influenza virus. Moreover, NMHC vaccination elicited CD4+ and CD8+ T-cell responses to clear the virus from infected tissue and prevent virus spreading. In conclusion, this study provided proof of concept for triggering both B cells and T cells immune responses against multiple influenza virus infection, and NMHC may be a potential candidate of universal broad-spectrum vaccine for various influenza virus prevention and therapy.
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Objective:Nuclear magnetic resonance spectroscopy (NMR) was used to detect the species and content of metabolites in urine of patients with inherited metabolic diseases, and to explore the application value of NMR technology in the diagnosis of inherited metabolic diseases.Methods:Urine samples were collected from 20 patients with inherited metabolic diseases diagnosed in Xinhua Hospital, Shanghai Jiaotong University School of Medicine from March to June 2019, including 9 cases of methylmalonic acidemia (MMA). NMR pulse length-based concentration determination and Gas chromatography mass spectrometry (GC/MS) semi-quantitative method were used to detect the composition of metabolites in urine samples of patients with inherited metabolic diseases, and the levels of abnormal metabolites in the two methods were analyzed.Results:NMR technology can detect the levels of characteristic metabolites significantly increased in the urine of patients with MMA, isovalerinemia, glutaric acidemia, propionic acidemia, 3-methylcrotonyl-CoA carboxylase deficiency, ornithine carbamyltransferase deficiency, Citrin deficiency, Canavan disease, tyrosinemia and lysinuria protein intolerance. The average is 8 times of the upper limit of the reference value, and the highest is 545 times. Compared to GC/MS, NMR technology can detect the levels of various metabolites such as organic acids, amino acids and sugars. In 9 cases of untreated MMA,the median levels of methylmalonic acid and 3-hydroxypropionic acid in NMR [1 800 (180-12 000) and 50 (0-270) mmol/mol Cr] were higher than the reference values (0-31, 0-35). The median levels of methylmalonic acid and methylmalonic acid in GC/MS [136.56 (43.79-518.67) and 4.87 (1.52-7.52)] were higher than the reference values (0-4 and 0-0.7).Conclusions:NMR and GC/MS technologies are specific for the diagnosis of organic acidemia. The primary component detected by GC/MS is organic acid. NMR technology can break through this limitation and measure the level of various metabolites in urine, which provides a more theoretical basis for the diagnosis and research of inherited metabolic disease.
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Objective:To investigate the treatment and prognosis of children with propionic acidemia (PA).Methods:This study involved 82 children with PA treated in the Department of Pediatric Endocrinol-ogy and Genetic Metabolism, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from December 2002 to June 2020. Clinical data, including manifestations, laboratory test results, treatment strategy, and follow-up data, were summarized and analyzed using t-test or Mann-Whitney U test. Results:(1) Among the 82 cases consisting of 50 (61.0%) boys and 32 (39.0%) girls, 59 (72.0%) were diagnosed after clinical onset; 22 (26.8%) were diagnosed by newborn screening, including eight asymptomatic ones; the other one (1.2%) was asymptomatic but confirmed after the diagnosis of PA in the patient's sibling. The average age at first onset was 4.5 months (2 d-5 years) in 73 subjects, of which 28 (38.4%) were early-onset PA (within three months after birth). (2) Cranial MRI was performed on 26 cases, and abnormality was identified in 19 (73.1%) cases. (3) Hyperlactatemia was found in 16 cases among 30(53.3%) who underwent relevant examination with the average lactic acid level of 3.5 (2.1-4.3) μmol/L, while 35 out of 40 patients (87.5%) had hyperammonemia with an average blood ammonia level of 105.4 (34-907) μmol/L. (4) Among the 28 early-onset PA cases, 16 (57.1%) died, and 12 (42.9%) survived. There was no significant difference in the serum propionylcarnitine level, propionylcarnitine to acetylcarnitine ratio, urine 3-hydroxypropionic acid, or methylcitrate level between the survival and death cases. (5) Genetic mutations were detected in 75 patients (91.5%), among which 26 (34.7%) carried PCCA gene mutations and 48 (64%) with PCCB gene mutations. One patient (1.3%) harbored one known pathogenic mutation in each of the PCCA and PCCB genes. All mutations were inherited from the parents. (6) Followed up to June 2020, 57 (69.5%) patients survived, and 25 (30.5%) died from multiple organ failure secondary to severe acidosis, including 16 early-onset and nine late-onset cases. Conclusions:The primary treatment of PA is dietary control. Most PA patients are diagnosed after clinical onset, but symptoms may recur and even have developmental retardation despite treatment. Some of those diagnosed through newborn screening are asymptomatic after treatment. Newborn screening using tandem mass spectrometry is recommended for early diagnosis and treatment of PA.
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The mortality rate of hepatocellular carcinoma (HCC) remains high, and although there have been several treatment methods, HCC patients still have poor treatment outcome and prognosis in clinical practice. Therefore, it is necessary to find a new drug for the treatment of HCC to improve patients’ survival rate. This article introduces a new antitumor drug, galangin, which can exert an antitumor effect by inhibiting cell proliferation, promoting apoptosis, inducing autophagy, and inhibiting metastasis. In addition, galangin can also inhibit angiogenesis in liver cancer, reverse multidrug resistance, and enhance the synergistic effect between drugs. Therefore, galangin is believed to have a promising future in clinical practice, and it is expected that more studies will focus on the anti-hepatoma cell mechanism of galangin to provide a scientific basis for the clinical translation of galangin.
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OBJECTIVE@#To summarize the clinical, biochemical and molecular characteristics of 8 patients with beta-ketothiolase deficiency (BKD).@*METHODS@#Clinical characteristics, biochemical markers detected by tandem mass spectrometry (MS-MS) and gas chromatography-mass spectrometry (GC-MS), and variations of ACAT1 gene of the 8 patients were reviewed.@*RESULTS@#Three patients were diagnosed by newborn screening and were asymptomatic. Five patients showed dyspnea and metabolic acidosis through high risk screening. Blood methylcrotonyl carnitine (C5:1) were 0.43 (0.20-0.89) μmol/L and 3-hydroxyisovaleryl carnitine(C5-OH) were 1.37 (0.98-3.40) μmol/L. Both were significantly higher than those of healthy controls (PG (p.N375S) variant, which accounted for 28.6% of all 14 mutant alleles. Four novel variants, namely c.229delG (p.E77KfsTer10), c.373G>T (p.V125F), c.419T>G (p.L140R) and c.72+1G>A, were discovered. Pathogenicity assessment of two highly conservative missense variants (p.V125F) and (p.L140R) were 0.994 and 1.0 (Scores obtained from PolyPhen2), and PROVEAN scores were -4.652 and -5.399, respectively. c.72+1g>a was suspected (by Human Splicing Finder) to alter the wild type donor motif and most probably affect the splicing.@*CONCLUSION@#Clinicians should consider MS/MS and GC/MS testing for those with unexplained neurological symptoms and metabolic acidosis in order to attain early diagnosis of BKD. Genetic testing should be used to confirm the diagnosis.
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Humans , Infant, Newborn , Acetyl-CoA C-Acyltransferase , Amino Acid Metabolism, Inborn Errors , Carnitine , Retrospective Studies , Tandem Mass SpectrometryABSTRACT
Objective To explore the clinical manifestations, treatment and outcomes of patients with c. 482G>A ( p. R161Q ) variant of MMACHC gene in cblC type methylmalonic acidemia ( MMA ) . Methods The clinical manifestations, mass spectrometry results, genotypes, treatment and outcomes of 75 patients with cblC type MMAcarryingc.482G>A(p.R161Q)variantwereretrospectivelyanalyzed.Results Ofthe75patients,57(76％) were from newborn screening and one of them had an onset. Among the rest 18 unscreened patients, 2 were diagnosed after their full sisters' or brothers' diagnosis, the others were clinical patients. There were 17 clinical patients, with the medium age of onset 12 years old (10 days～26 years old). 12 late onset patients (70.6％) presented with poor academic performance, memory loss, poor expression, and decreased exercise capacity, while 5 early onset patients (29.4％) presented with convulsion and delay of development. All patients were vitamin B12-responsive. The levels of blood propionylcarnitine, the ratio of propionylcarnitine to acetylcarnitine, urinary methylmalonic acid and methyldecanoic acid, and plasma homocysteine were significantly decreased after treatment (P< 0.01). All patients diagnosed from newborn screening had normal development. However, only 3 clinical patients had a rather normal outcomes and the others remained different levels of intelligence and ( or ) motor dysfunction after treatment. Conclusion The c.482G>A ( p. R161Q) variant of MMACHC gene is associated with late onset cblC type MMA. Patients with this variant have a better response to hydroxycobalamin than other variants. The outcome of patients diagnosed from the newborn screening is good. When symptoms occur, the disability rate is often high. Therefore, newborn screening is a recommended method to prevent this disease.
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<p><b>OBJECTIVE</b>To determine the genetic etiology and clinical characteristics of 2 boys featuring development delay (DD).</p><p><b>METHODS</b>Routine chromosomal banding was performed to analyze the karyotypes of the patients and their parents. Single nucleotide polymorphism array (SNP array) analysis was employed to identify pathogenic deletion/duplication of chromosomes, and quantitative real-time PCR (qPCR) was performed to confirm the results.</p><p><b>RESULTS</b>Patient 1 showed a global developmental delay, especially impaired language development, seizures, behavioral problems belonging to the autism spectrum and mild facial dysmorphism. Patient 2 mainly presented with severely delayed speech and moderate intellectual disability, but did not have obvious facial dysmorphism and autistic-like behavior. The diagnosis of 22q13 syndrome was established based on identification of a heterozygous microdeletion at chromosome 22q13.33 in both patients (69 kb and 587 kb, respectively) by the SNP array analysis. Both patients had deletions of SHANK3 and ACR, which are located at the end of 22q. Quantitative real-time PCR verified that the deletion of SHANK3 gene in both patients were de novo in origin.</p><p><b>CONCLUSION</b>Two cases of 22q13 deletion syndrome have been diagnosed by SNP array analysis. Deletion of SHANK3 gene may be the major contributor to the clinical manifestations of the patients. SNP array analysis can facilitate discovery of microdeletions, which has played an important role in the diagnosis and genetic counseling for the family.</p>
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CAR-T cell therapy that targets surface antigens to kill tumor cells specifically has recently become another cornerstone in tumor immunotherapy. In this study, a lentiviral expression plasmid of CAR targeting human epidermal growth factor receptor 2 (HER2) was constructed by genetic engineering. The recombinant plasmid was co-transfected with other packaging plasmids into HEK293T cells by calcium phosphate precipitation to generate lenti-car, which are CAR lentiviral particles. HER2-specific CAR-T cells were obtained by transducing human peripheral blood mononuclear cells with lenti-car. Their specific inhibitory effects on HER2-positive and HER2-negative tumor cells were analyzed in vitro. The constructed CAR-T cells were specifically activated by HER2-expressing tumor cells as indicated by secretion of IFN-γ and IL-2. The inhibitory rate on HER2-positive SK-OV-3 cell line was (58.47±1.72)%, significantly higher than that on the mock-treated control group (P<0.05). The inhibitory rate on HER2-negative K562 cell lines was (11.74±2.37)%, which was not significantly different from that on the control group (P>0.05). Furthermore, when we transfected a HER2-expressing vector into K562, the inhibitory rate increased to (30.41±7.59)%, which was higher than that on HER2-negative K562 (P<0.05). Thus, the constructed second-generation HER2-specific CAR-T cells specifically suppressed growth of tumor cells overexpressing HER2 protein, suggesting that HER2-specific CAR-T cells might prove useful for immunotherapy of HER2-positive cancer.
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Objectives@#To investigate the prevalence rate and clinical characteristics of familial hypercholesterolemia (FH) in Chinese patients undergoing coronary angiography due to angina-like chest pain.@*Methods@#From March 2011 to December 2016, a total of 9 908 consecutive patients undergoing coronary angiography in Fuwai Hospital due to angina-like chest pain were enrolled. The age of enrolled patients was (56.6±11.1) years old, and 6 782 cases (68.4%) were male. The patients were divided into two groups: FH group (n=271) and non-FH group (n=9 637) according to the Dutch Lipid Clinic Network diagnostic criteria. A retrospective analyze was performed on the baseline features between the two groups including lipids levels, coronary artery disease (CAD) characteristics, and lipids-lowering treatments.@*Results@#In the total cohort, the prevalence of definite/probable FH was 2.7% (271/9 908). The incidence of premature coronary artery disease (PCAD) (women < 60 years old, or men < 55 years old) was higher in patients with FH than that in patients without FH (70.2%(201/271) vs. 44.5% (4 287/9 637); χ2=93.738, P<0.001). Patients with FH had higher level of TC and LDL-C when compared with patients without FH ((6.74±2.48) mmol/L vs. (4.15±1.10) mmol/L; (4.53±2.39) mmol/L vs. (2.52±0.97) mmol/L; t=19.403, 22.233, P<0.001, respectively). Additionally, 84.9% (230/271) of FH patients were treated with statin at different intensities, but none of them achieved the LDL-C<2.6 mmol/L.@*Conclusions@#Chinese patients with familial hypercholesterolemia not only showed a high presence of PCAD and higher lipids levels, but also exhibited a low rate of achievement of low-density lipoprotein cholesterol targets despite statin therapy. Our results thus highlight the importance of early diagnosis and intensive treatment of FH patients.
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Objective To investigate the characteristics of glycogen storage disease type IV (GSD IV) clinically, in laboratory tests and in gene mutation. Methods The clinical manifestations, biochemical indexes, activity of chitotriosidase, and the follow-up of the treatment in 5 cases of GSD IV were analyzed. Results Five patients (3 boys and 2 girls) aged 4 months - 5 years presented hepatosplenomegaly and elevated liver enzyme levels for 2 months at hospital visit. Two patients had motor developmental delay and weakness but their creatine kinase (CK) level were normal. Glycogen storage and liver fibrosis were observed in the liver biopsy in 4 patients. Target sequencing found that all 5 children carried the complex heterozygous mutation of the GBE1 gene with 2 reported mutations(p.R515C,p.R524Q)and 7 novel mutations.The novel mutation contains 5 missense mutations (p.I460T, p.F76S, p.F538V, p.L650R, p.W455R), one insertion mutations (c.141_142insGCGC), and one large fragment deletion (exon 3-7). Therefore, diagnosis of liver type of GSD IV was confirmed in those children. Two patients died of liver cirrhosis. The liver transplantation was performed due to liver cirrhosis in one patient whose chitotriosidase activity increased obviously before transplantation and decreased significantly after the transplantation and liver enzyme levels were returned to normal 4 months after transplantation. In the other two patients their growth and liver enzyme levels were normal;one had not received special treatments while the other was treated with raw corn starch and level of chitotriosidase was normal. Conclusions The clinical manifestations of GSD IV are heterogeneous. Target sequencing can be used for fast and noninvasive diagnosis of GSD IV. Chitotriosidase activity is useful in the prognosis assessment for GSD IV.
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Objective To explore the value of the combination of homocysteine analysis, liquid chromatography tandem mass spectrometry(LC-MS/MS)and gas chromatography mass spectrometry(GC/MS)in the prenatal diagnosis of combined methylmalonic acidemia and homocystinuria(cblC defect)in amniotic fluid.Methods This is a retrospective study of 187 cases of pregnancies that came to our hospital for prenatal diagnosis between 2014/01-2017/03,among which 78 cases′probands were cblC defect patients and 109 cases′probands were not organic academia patients(control group).Amniotic fluid samples from pregnant women were obtained at 16 -24 weeks of gestation.Propionylcarnitine(C3)and acetylcarnitine (C2)were measured by LC-MS/MS, methylmalonic acid and methylcitric acid were analyzed by GC /MS, and homocysteine was determined by fluorescence polarization immunoassay.Some pregnancies received MMACHC gene sequencing with cultured cells from amniotic fluid.Data were analyzed using Mann-Whitney U and Kruskal-Wallis H tests.Results Among those 78 pregnant women whose probands were diagnosed to be cblC defect,24 cases were diagnosed to be cblC defect(positive group)and 54 pregnant women were diagnosed to be negative(negative group).In positive group, levels of homocysteine, C3, C3/C2, methylmalonic acid and methylcitric acid were all significantly higher than their normal reference ranges, negative group and control group(P values are 0.00).Cases that were diagnosed to be cblC defect by MMACHC gene sequencing were all turned out to be positive in the tests of the above metabolites in amniotic fluid.Cases with negative results of the metabolites were all excluded to be cblC defect by gene sequencing. Besides,2 cases of pregnancies were diagnosed to be positive by homocysteine and mass spectrometric analysis while only one mutation were detected by gene sequencing.Conclusions The combination of homocysteine, LC-MS/MS and GC/MS analysis in amniotic fluid turns out to be reliable for prenatal diagnosis of cblC defect,which may further cover the defect of prenatal diagnosis of those pregnancies whose probands′gene mutation is unknown.
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Objective To conduct a scoping review to systematically review the literature reporting enteral feeding protocol in critical ill children. And extract elements of enteral feeding protocol. Methods The database of BIOSIS Previews, PubMed, MEDLINE, EMbase, China Biology Medicine Disc, China National Knowledge Infrastructure and Wan Fang data were searched. Data were extracted on the information of article, elements of enteral feeding, evaluation of feeding etc. Results Three historical controlled studies, three case-control studies, two cohort studies, one narrative review and one qualitative study were included. Totally 16 elements were got, such as nutrition evaluation, estimated energy requirement, contraindication, feeding intolerance etc. And all protocols defined advancement and feeding intolerance. Conclusions Enteral feeding protocol has been used in most PICUs to optimize nutrition. But we observed variability in the composition of protocols and lack of evidence-based recommendations in few elements.
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Objective To analyze the influence of validating the parental origin to the interpretation of clinical pathogenicity of total 54 copy number variations(CNV)with different clinical significance in 46 patients undergo chromosomal microarray analysis(CMA).Methods A retrospective study.This study enrolled 46 patients conducted in Department of Pediatric Endocrinology and Genetics of Shanghai Xinhua Hospital during the period of August 2014 to December 2015,involving 54 different CNVs detected by CMA.The parental origin of CNVs was examined by CMA or quantitative real-time polymerase chain reaction.Results Totally 54 different CNVs were found in 46 patients by CMA.Seventeen out of the 54 CNVs were pathogenic variations.After validating the parental origin,14 CNVs were proved de novo mutation,while 3 CNVs have maternal origin including 1q21.1 deletion syndrome,Xq27.3q28 and Xq22.1q22.3 duplications which inherited from maternal X chromosome.CNVs of 1q21.1 deletion syndrome often inherited from parents,and no phenotype appears on mother which may be due to the deactivation mechanism of duplications on mother′s X chromosome.Therefore,these 17 pathogenic variations were still considered to be clinical pathogenic significance after validating the parental origin.Ten out of 54 CNVs were variants of uncertain significance-likely pathogenic.After parental original validation,3 CNVs were proved de novo mutation considering likely pathogenic significance,while 7 CNVs have parental origin still judged to be unknown clinical pathogenicity.Twenty-seven out of 54 CNVs were variants of uncertain significance.After validating the parental origin,only 1 CNV was proved de novo mutation considering likely pathogenic significance,while all the others had parental origin considered to be variations likely benign.Conclusion CNVs reported as likely pathogenic should be validated the parental origin in order to further study their clinical pathogenicity,while variants of uncertain significance can preliminary clear its nature by validating parental origin.
