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BACKGROUND: Malonyl-CoA decarboxylase (MLYCD) deficiency, also known as malonic aciduria (MAD), is a rare autosomal recessive inherited metabolic defect. In this study, we aimed to investigate the clinical and molecular features of five patients with MAD in order to increase clinicians' awareness of the disease. METHODS: Sanger sequencing was used to detect and genetically analyze the MLYCD variations in the preexisting patients and their parents. RESULTS: Five patients with MAD (5 months to 9.6 years old; two males and three females) rarely exhibited metabolic decompensation episodes or seizures. All patients exhibited varying degrees of developmental delay and hypotonia. Our study expands the spectrum of variants of the MLYCD gene. MLYCD gene variations were detected in all five patients, and five new variants were identified: c.60delG (p.Arg21Glyfs*52), c.928C > T (p.Arg310*), c.1293G > T (p.Trp431Cys), c.721T > C (p.Ser241Pro), and Exons 4-5 deletion. Additionally, there is no correlation between various genotypes and phenotypes. CONCLUSION: A high-medium-chain triglyceride and low-long-chain triglyceride diet supplemented with L-carnitine was effective in most patients and may improve cardiomyopathy and muscle weakness. Newborn screening may aid in the early diagnosis, treatment, and prognosis of this rare disorder.
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To develop a caregiver parenting behavior scale for children aged 2 to 6 years, and to verify its reliability and validity. This study recruited 1 350 caregivers of children aged 2 to 6 years. The item discrimination analysis and exploratory factor analysis were used to analyze the structure, dimensions and items of the scale. Homogeneity reliability, split-half reliability and test-retest reliability were used to analyze the reliability of the scale. Content validity and construct validity were used to analyze the validity of the scale. The results showed that the final scale contained 7 dimensions and 45 items. Cronbach's α coefficient of the total scale was 0.945; the coefficient of split half was 0.899; the test-retest reliability analysis showed that the correlation coefficients between the two tests were 0.893 (total score), 0.854 (social), 0.832 (language), 0.871 (gross motor), 0.893 (fine motor), 0.862 (cognitive), 0.832 (self-care), and 0.872 (sensory). The content validity analysis was carried out by two rounds of expert argumentation using Delphi expert consultation method. The Kendall coefficient of the items score in two rounds of Delphi expert consultation was 0.813 (P<0.01). The structure validity analysis showed that there were significant correlations between each dimension and the total scale, also between each dimension of the scale, and the extracted average variance values of each dimension was greater than the correlation coefficients between this dimension and other dimensions. In conclusion, the reliability and validity of the scale are qualified. It can be used as a tool to evaluate and guide the parenting behavior of caregivers of children aged 2 to 6 years.
Subject(s)
Caregivers , Parenting , Humans , Child , Caregivers/psychology , Reproducibility of Results , Surveys and Questionnaires , Factor Analysis, Statistical , Psychometrics/methodsABSTRACT
Objective: To explore the clinical characteristics, genotypes and long-term outcomes of individuals with 3-methylglutaconic aciduria. Methods: The clinical features, biochemical data, genetic test results and treatment outcomes of six children with 3-methylglutaconic aciduria admitted to the Department of Endocrinology, Genetics and Metabolism, Xinhua Hospital from February 2017 to February 2019 were retrospectively analyzed and the Gesell developmental diagnosis schedule was performed to evaluate the development of four patients. Results: Among 6 children with 3-methylglutaconic aciduria 2 were males and 4 were females.Four cases had 3-methylglutaconic aciduria type â and 2 cases had 3-methylglutaconic aciduria with deafness,encephalopathy, and Leigh-like syndrome. Five of 6 patients were detected by newborn screening among whom 4 remained asymptomatic, and only one had a postmortem diagnosis. Among them, 4 patients remained asymptomatic, while two presented with clinical symptoms such as jaundice and dyspnea and the age of disease onset was 1 and 2 days respectively. The concentration of 3-methylglutaconic acid in urine of all affected individuals was between 22.38 and 77.09 mmol/molCr, which was above the normal value. Genetic tests were performed for all patients. Eleven variants were identified in 2 genes, of which 10 variants were novel and only c.442C>T p.(R148X) has been previously reported; Seven variants (c.656-2delA, EX5-EX6 Del, c.942+3A>G, c.373C>T p.(R125W), c.895-3C>G, c.667C>T p.(R223X) and c.894+5G>A) were in AUH gene. The others (c.548G>A p.(R138Q), c.442C>T p.(R148X), c.1339C>T p.(R447X) and c.973dupA p.(M325Nfs*5) were in SERAC1 gene. After being treated with leucine diet restriction and L-carnitine, 4 patients with AUH gene variation who were from asymptomatic phase developed normally, whereas those 2 patients with SERAC1 gene variation had a poor prognosis. During the follow-up, 2 patients exhibited varying degrees of psychomotor retardation, the rest had normal course of development. Conclusions: There are significant clinical heterogeneities among individuals with 3-methylglutaconic aciduria. The most common pathogenic variants are splicing variations, followed by nonsense, missense and frameshift mutations. Leucine-free diet and oral L-carnitine therapy are effective for some patients. Newborn screening is essential for early diagnosis and improvement of prognosis.
Subject(s)
Brain Diseases , Metabolism, Inborn Errors , Child , Female , Glutarates , Humans , Infant, Newborn , Male , Mutation , Neonatal Screening , Retrospective StudiesABSTRACT
The clinical and biochemical data and gene sequencing results of patients with carnitine palmitoyltransferase 1A deficiency were analyzed, in order to improve the understanding of the disease. Six patients (5 males and 1 female, aged from 1 to 8 years old) with carnitine palmitoyltransferase 1A deficiency from Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital between 2008 and 2019 were included. Two cases were detected by neonatal screening and had no clinical symptoms. The remaining 4 cases all showed seizures induced by fever, vomiting or diarrhea. All the 6 patients showed increased serum free carnitine (C0), decreased hexadecanoylcarnitine (C16) and octadecanoylcarnitine (C18), and increased C0/(C16+C18). Meanwhile, compound heterozygous mutations of CPT1A gene were detected in all 6 patients, of which 2 were reported mutations (c.281+1G>A and c.968-8C>T), and 10 were new mutations. The new mutations included 6 missense mutations, 1 nonsense mutation, 1 deletion mutation and 2 splicing mutations. Detection of free carnitine and acyl carnitine by tandem mass spectrometry is helpful for early screening and diagnosis of carnitine palmitoyltransferase 1A deficiency.
Subject(s)
Hypoglycemia , Lipid Metabolism, Inborn Errors , Aged , Carnitine , Carnitine O-Palmitoyltransferase/genetics , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Lipid Metabolism, Inborn Errors/genetics , Male , Mutation , Neonatal ScreeningABSTRACT
Objective: To analyze the incidence of eating problems and risk factors in children aged 1-6 years, and provide evidence for formulating relevant prevention and control strategies. Methods: From June to December 2019, two community health service centers and two kindergartens were randomly selected in Shunyi district of Beijing by using stratified random cluster sampling method. Self-designed questionnaires were used to collect data on individual information, family information, and the incidence of eating problems and related factors. Multivariable logistic regression analysis was conducted to identify related factors. Results: A total of 2 391 valid questionnaires were returned, the analysis result indicated that 1 432 children had at least one eating behavior problem, the incidence rate was 59.9%. The most common eating problem was inattention while eating (48.8%), followed by irregular eating position (14.0%), picky eaters (13.0%), excessive eating time (11.2%), excessive snacks intake (9.0%), and soup with rice (4.6%). The mother's education level, family income level, main caregivers and family members' attitudes toward child's eating were related factors for eating behavior problems in children. Mothers with high education level (OR=0.528, 95%CI: 0.431-0.647) and family with high income level (OR=0.656, 95%CI: 0.473- 0.909) were the protective factors for child's poor eating behaviors. Grandparent caring (OR=1.366, 95%CI: 1.151-1.622), coaxing or forcing child to eat (OR=1.581, 95%CI: 1.284-1.947) were the risk factors for child's poor eating behavior. Conclusion: The incidence of eating problems was high in children aged 1-6 years. It is necessary to strengthen the intervention in families with low-income and low-education levels and children raised by grandparents to reduce the incidence of poor eating behaviors in children.
Subject(s)
Feeding and Eating Disorders , Beijing/epidemiology , Child , Child, Preschool , Feeding and Eating Disorders/epidemiology , Humans , Incidence , Infant , Risk FactorsABSTRACT
Objective: To understand the gender selection and prognosis of children with 46, XY disorders of sex development (DSD) after surgery, and to provide reference for future clinical decision-making. Methods: Data of 85 (80 males and 5 females) postoperative patients with 46, XY DSD with follow-up age of 6(4,11) years who were treated at the Department of Endocrinology, Genetics and Metabolism of Beijing Children's Hospital Affiliated to Capital Medical University during the period from September 2009 to April 2018 were retrospectively analyzed. The patients were grouped based on diagnosis. The basis of postoperative gender selection, patient satisfaction and related factors, gender characteristics, and adolescent development were analyzed. The Pre-school Activities Inventory or the Children's Sex Role Inventory were used in the analysis of gender tendency. Mann-Whitney U test was used to compare postoperative gender satisfaction of different factors. The Kruskal-Wallis method was used to compare the postoperative gender satisfaction of each group. Fisher's test was used to compare the follow-up status of male children over 11 years old in each group. Results: Among the 85 patients, 62 individuals were raised as girls after birth, 9 were facultative and 14 as boys. According to the diagnosis, there were 31 individuals in group 1 (with 5α-reductase deficiency), 11 individuals in group 2 (with androgen insensitivity syndrome), 9 individuals in group 3 (with NR5A1 gene mutation), 4 individuals in group 4 (with hypergonadotropic gonadal dysplasia), and 30 indiviudals in group 5 (with unclear diagnosis and normal human choionic gonadotophin test). Among the 71 children who were raised as girls or facultative children after birth, 66 selected as boys, and 5 continued as girls (among them, 3 individuals were female with passive selection, and 2 individuals of testicular dysplasia with uterus in group 4 and 5 were female with active selection). Among the 71 patients faced with gender selection, only one was unsatisfied, that was a postoperative female. There was no significant difference in postoperative gender satisfaction among different disease diagnoses, surgical age and penis length (χ(2)(H)=6.007, P=0.199; Z=-0.860, P=0.390; Z=-0.438, P=0.661). Fifty-nine of the 85 cases completed the gender tendency scale test and 46 cases (78%) were consistent. In the male patients, 45 cases were consistent. Thirteen inconsistent patients (22%) were female or facultative after birth who were 5 years old or older. There was no stigmatization noticed in the inconsistent patients' daily life and school social settings. There were 22 male patients aged 11 years and older. They were 13(12,16) years old. Fourteen (64%) individuals' penile length reached the normal minimum, 15 (68%) individuals' testicular volume were equal or more than 4 ml, 16 (73%) individuals' sex hormones entered puberty levels, 12 (55%) individuals had been spermatorrhea, the age of first spermatorrhea was (13.3±2.4) years. They were satisfied and adaptable after surgery. There was no significant difference in the above indicators among the groups (χ²=2.999, P=0.694; χ²=7.278, P=0.086; χ²=5.597, P=0.358; χ²=6.904, P=0.127). Conclusions: The appropriate gender of 46, XY DSD patients was selected according to gonadal status after diagnosis. Regardless the diagnosis, the age of operation and the length of the penis at the first diagnosis, male patients were satisfied with the gender after the operation. A few of patients were inconsistent with the results of gender tendency scale test who were raised as girls or facultative children after birth, and they required sustained special attention. Some of the children showed natural adolescent development in males, and the prognosis may be ideal.
Subject(s)
Disorder of Sex Development, 46,XY/surgery , Disorders of Sex Development/surgery , Genitalia/surgery , Sexual Development/physiology , Sexual Maturation/genetics , Adolescent , Child , Child, Preschool , Disorders of Sex Development/genetics , Female , Follow-Up Studies , Gender Identity , Humans , Male , Postoperative Complications , Quality of Life , Retrospective StudiesABSTRACT
Objective: Regurgitation, infantile colic, and functional constipation are common gastrointestinal symptoms in childhood, the aim of this study was to explore the prevalence and distribution of these symptoms in China. Methods: A screening program in infants aged 0 to 3 years selected through stratified cluster random sampling was carried out in 7 cities in China. Questionnaires were filled, and then diagnosis were made according to Rome â £ criteria. Areas, (urban-rural), age and gender distribution of prevalence of childhood common gastrointestinal symptoms were analyzed. Results: Totally, 20 932 effective questionnaires were returned. The total number of infants aged 0 to 1 years was 10 193. Regurgitation was diagnosed in 1 960 infants, with the prevalence of 19.2%, among infants aged 0 to 3 months that had highest prevalence (29.8%). The prevalence decreased with age, and differences among different age groups showed significant. For infantile colic, 4 470 infants aged 0 to 5 months were analyzed and the prevalence of infantile colic was 7.3%. The prevalence of infantile colic was the highest in infants aged 1 to 2 months (10.0%). Age specific difference was significant. Of all the infants, functional constipation was diagnosed in 1 755 infants with the prevalence of 8.4%, and the lowest prevalence was found in infants aged 0 to 3 months (6.2%), and the highest prevalence was in infants aged 30 to 36 months (10.0%). The differences in different age group were significant. Conclusion: Symptoms of regurgitation, infantile colic, and functional constipation are common in infants in China, with age specific difference in prevalence of the symptoms.
Subject(s)
Colic/epidemiology , Constipation/epidemiology , Gastrointestinal Diseases/epidemiology , Population Surveillance , Age Distribution , Child , Child, Preschool , China/epidemiology , Cities , Humans , Infant , Infant, Newborn , Prevalence , Surveys and QuestionnairesABSTRACT
Objective: To investigate the value of amniotic fluid metabolite detection by mass spectrometry combined with gene mutation analysis in the prenatal diagnosis of glutaric acidemia type â (GA-â ). Method: From January 2009 to December 2016, Department of Pediatric Endocrinology and Genetic, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine carried out prenatal diagnosis for 24 cases of pregnant women with GA-â proband. 24 pregnant women without organic acidemia proband for conventional prenatal diagnosis at the same period were used as the control group. The pregnant women of the two groups had the amniocentesis at 16 to 20 weeks of gestation.The levels of glutaryl carnitine (C5DC) and octanoylcarnitine (C8) in amniotic fluid were detected by tandem mass spectrometry, and the levels of glutaric acid was determined by gas chromatography-mass spectrometry. All the amniotic fluid cells underwent GCDH gene testing. Result: A total of 4 cases of fetuses were diagnosed by gene mutation analysis combined with mass spectrometry detection, the levels of C5DC (1.58(0.89-2.85) µmol/L), C5DC/C8 (19.74(12.40-25.93))and glutaric acid (129.96 (90.09-66.02) mmol/mol Cr) were significantly higher than the upper limit of the reference, of which in one case with the proband only on mutation was detected, and in the amniotic fluid cells also only one mutation was detected, the diagnosis was made according to the significantly increased levels of amniotic fluid C5DC, C5DC/C8 and glutaric acid. Twenty cases of fetuses were identified as non-GA-â children, of whom in 2 cases of proband only one mutation was detected, and also in amniotic fluid cells one mutation was detected, in 2 cases the diagnosis was excluded because the normal levels of C5DC, C5DC/C8 and glutaric acid. There were 2 cases whose levels of C5DC or glutaric acid were slightly higher than the upper limit of the reference, but the diagnosis was excluded according to genetic testing. Conclusion: Prenatal diagnosis cannot be made by gene analysis when the proband mutation is not clear, and it cannot determine whether the fetus is patient when the mass spectrometry detection of amniotic fluid metabolite is mildly abnormal, while mass spectrometry detection of amniotic fluid C5DC, C5DC/C8 and glutaric acid levels combined with GCDH gene analysis can make up the deficiencies, and make the prenatal diagnosis of GA-â more reliably.
Subject(s)
Amino Acid Metabolism, Inborn Errors , Brain Diseases, Metabolic , Genetic Testing , Glutaryl-CoA Dehydrogenase/deficiency , Prenatal Diagnosis , Amino Acid Metabolism, Inborn Errors/diagnosis , Amino Acid Metabolism, Inborn Errors/genetics , Brain Diseases, Metabolic/diagnosis , Brain Diseases, Metabolic/genetics , China , Female , Glutaryl-CoA Dehydrogenase/genetics , Humans , PregnancyABSTRACT
OBJECTIVE: To detect large genomic deletions or duplications of ornithine transcarbamylase (OTC) gene by multiplex ligation-dependent probe amplification (MLPA). METHOD: Thirty cases of suspected OTC deficiency (OTCD) patients based on tandem-mass spectrum results were recruited in Xinhua Hospital from 2012 to 2014, among whom 13 were male and 17 were female. Sanger sequencing of OTC gene revealed mutations in 23 cases. MLPA was performed in the patients whose previous Sanger sequencing failed to detect any disease-causing mutation. The samples were treated via the steps of DNA degeneration, the probe hybridization, connecting the hybridization probe, PCR amplification and capillary electrophoresis. The data were analyzed using Coffalyser software. RESULT: Abnormal MLPA results were found in 5 patients without mutation detected in previous Sanger sequencing. Patient 1, a 9-year old girl, had a heterozygous deletion of Exon 2-4. Patient 2, a male newborn, died 10 days after birth. The examination of the mother's sample by MLPA revealed a heterozygous duplication of exon 2-6. Patient 3, a 10-day old boy, was found to harbor a hemizygous deletion of exon 7-10. Patient 4, a 2-year old girl, harbored a heterozygous deletion of exon 1-4. The fifth patient died at the age of 6 years, and his mother carried a heterozygous duplication of exon 1-4. CONCLUSION: MLPA can be helpful in detecting the OTC gene defects, particularly for OTCD patients without mutation detected by Sanger sequencing.
Subject(s)
Multiplex Polymerase Chain Reaction , Ornithine Carbamoyltransferase Deficiency Disease/diagnosis , Ornithine Carbamoyltransferase Deficiency Disease/genetics , Exons , Female , Heterozygote , Humans , Infant, Newborn , Male , Mutation , Sequence DeletionABSTRACT
About thirty thousands horses were affected and hundreds of them died in an epidemic caused by equine 2 influenza virus (H3N8) in China. The estimated morbidity and mortality accounted for 81% and 2%, respectively. The viral protein and RNA electrophoresis patterns revealed that the new isolates were antigenically different from the prototype strain influenza A/eq/Miami/1/63(H3N8). Therefore, the representative strain of the equine 2 subtype of influenza A virus recommended for producing reference reagents, vaccines, and for serological diagnosis must have been altered by antigenic drift.