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Objective To investigate the effect of IGF1R β subunit mutants sb-IGF1R and ma-IGF1R on the biological behavior of osteosarcoma 143B cells. Methods We designed and constructed sb-IGF1R and ma-IGF1R fragments. They were cloned into adenovirus AdEasy shuttle plasmid, to obtain Ad-sbIGF1R and Ad-maIGF1R. We observed the proliferation, migration and apoptosis of the osteosarcoma cells transfected with Ad-sbIGF1R, Ad-maIGF1R and Ad-IGF1R. The Ad-sbIGF1R, Ad-maIGF1R and Ad-GFP nude mouse models were constructed to evaluate the tumor growth in vitro. Results By plasmid PCR, IGF-1R β subunit mutant was overexpressed in osteosarcoma cells. Ad-sbIGF1R and Ad-maIGF1R significantly inhibited the proliferation and migration of osteosarcoma cells, and promoted cell apoptosis, and inhibited tumor growth in subcutaneous tumor-bearing nude mouse models. Conclusion IGF1R β subunit mutants inhibit the proliferation and migration of osteosarcoma cells and induce cell apoptosis.
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Objective:To investigate the effect of a degradable high-purity magnesium screw in fixing the greater trochanter bone flap of a lateral circumflex femoral artery transverse branch in the treatment of ischemic necrosis of femoral head in young and middle-aged adults.Methods:From February 2017 to February 2019, 12 cases (15 hips) of young and middle-aged patients with avascular necrosis of femoral head were treated in the Department of Orthopaedic of Affiliated Zhongshan Hospital of Dalian University. The age of patients was 30-53 years old. According to Association Research Circulation Osseous (ARCO), 2 hips were graded in stage II b, 4 in ARCO II c, 1 in ARCO III a, 5 in ARCO III b, 2 in ARCO III c and 1 in ARCO IV. The greater trochanter bone flap with a lateral circumferential vascular branch was used to fill the necrotic area, and fixed by a biodegradable high purity magnesium screw in the bone flap transfer. At 3, 6 and 12 months postoperation, the patient came to the hospital outpatient clinic for follow-up, and then were reviewed once a year. Imaging efficacy was evaluated by comparing preoperative and postoperative imaging. The Harris score and Visual Anoalogue Scale (VAS) score were tested at 12 and 24 months after surgery. The Harris score and VAS score before and after surgery were compared by Friedman test, and P<0.05 was considered statistically significant. Results:All 12 patients (15 hips) were entered in the 24-36 months of follow-up. At 12 and 24 months after surgery, Harris score was found at 87 (86, 92) and 90 (87, 92) respertively, which were both higher than that before surgery [59 (52, 74)] with a significant statistical difference ( Z=-3.743, Z=-4.473, P<0.05). However, there was no significant difference in Harris scores between 12 and 24 months after the surgery ( Z=-0.730, P>0.05). At the 12 and 24 months after surgery, VAS score was found at 3 (2, 3) and 2 (1, 3) respertively, which were both lower than that before surgery [6 (5, 6) ] with a significant statistical difference ( Z=-3.560, Z=-4.656, P<0.05). There was no statistical difference in VAS scores between 12 and 24 months after surgery ( Z=-1.095, P>0.05). X-ray and CT scan showed that the bone flaps healed well and the areas of osteonecrosis were repaired. Thirteen femoral heads were in good shape, and 2 femoral heads had further collapse of hips. No patients underwent joint replacement surgery at the time of last follow-up. Conclusion:Fixation of the greater trochanter flap of lateral circumflex femoral artery transverse branch with a degradable high-purity magnesium screw can ensure the healing of the flap at the implantation site and avoid the displacement and shedding of the flap. It is a new therapeutic option to treat the avascular necrosis of femoral head of young and middle-aged people.
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DNA methylation as an important aspect of epigenetics plays an important role in spermatogenesis and embryonic development. In recent years, researchers have found that male infertility, in particular abnormal semen quality, is related to abnormal DNA methylation. To further delineate the pathogenesis of male infertility and inspire new ideas for the treatment of male infertility, a comprehensive review over the correlation between abnormal methylation of imprinted genes, repetitive DNA elements and non-imprinted genes, semen quality (including sperm count, morphology, and vitality) and male infertility is provided.
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Humans , Male , DNA Methylation , Infertility, Male/genetics , Semen Analysis , Sperm Count , Spermatogenesis , Spermatozoa/pathologyABSTRACT
Objective:To explore the clinical characteristics, plasma levels of hydrogen sulfide(H 2S) and the relationship between the genotype and phenotype of cardiovascular involvement in children with methylmalonic acidemia and homocystinemia. Methods:The clinical and laboratory data of 66 outpatients diagnosed with methylmalonic acidemia combined with homocystinemia in Department of Pediatrics, Peking University First Hospital from January 2014 to July 2014 were collected and analyzed respectively, and the patients were divided into 2 groups: cardiovascular involvement group (10 cases) and non-cardiovascular involvement group(56 cases). The differences in the clinical characteristics, plasma levels of H 2S and genotypes were compared between 2 groups. Results:(1) There were 45 cases of early-onset children under 1 year old, including 4 cases of cardiovascular system involvement and 41 cases of non-cardiovascular system involvement.Twenty-one cases had onset above 1 year old, including 6 cases of cardiovascular system involvement and 15 cases of non-cardiovascular system involvement. There were 44 male children, including 8 cases with cardiovascular system involvement and 36 cases without cardiovascular system involvement; 22 cases female children, including 2 cases with cardiovascular system involvement and 20 cases without cardiovascular system involvement. There was no significant difference in onset age and gender distribution between the 2 groups ( χ2=2.910, 0.368, all P>0.05). (2)In the 10 cases with cardiovascular involvement, there were 3 cases with hypertension, 2 cases with hypertension combined with pulmonary hypertension, 2 cases with mild myocardial hypertrophy, 1 case with atrial septal defect combined with pulmonary hypertension, 1 case with pulmonary hypertension, 1 case with myocardial noncompaction.Compared with the non-cardiovascular involvement group, the proportion of kidney involvement was increased and that of nervous system was decreased in cardiovascular system involvement group( χ2=20.34, 5.79, all P<0.05), the proportion of hematological system involvement between the 2 groups had no significant differences ( χ2=1.28, P>0.05). The plasma levels of hydrogen sulfide of children with cardiovascular involvement was significantly lower than that of non-cardiovascular involvement[(33.8±3.6) μmol/L vs.(39.3±5.2) μmol/L, t=-3.22, P<0.01]. (3) MMACHC gene mutation (cblC type) was identified in all 46 patients.It was found that the most common type of gene mutation was c. 80A>G in cardiovascular involvement group, while c. 609G>A was the most common type of gene mutation in non-cardiovascular involvement group. Conclusions:The clinical manifestations of children with methylmalonic acidemia and homocystinemia involving cardiovascular system are multiple and prone to multiple system involvement, especially renal involvement.A decrease in plasma hydrogen sulfide levels may be involved in the involvement of its cardiovascular system.The MMACHC gene c. 80A>G mutation is the most common genetic mutation site in children with cardiovascular involvement with methylmalonic acidemia and homocystinemia.
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Objective Analyze the effect of emergency thrombolytic therapy on door to needle time (DNT) in patients with acute ischemic stroke (AIS) and effect.Method Selected 182 cases of AIS patients underwent intravenous thrombolysis at the First Hospital of Qinhuangdao from May 2015 to June 2017.Thrombolytic therapy group (83 cases),for the May 2015-May 2016 after neurological consultation intravenous thrombolysis patients;Emergency thrombolytic group(99 cases),for the June 2016-June 2017 emergency thrombolysis group Emergency Department of intravenous thrombolysis patients.Compare the two groups of DNT,thrombolytic therapy 24 h symptomatic hemorrhage conversion rate,Thrombolysis 24 h,7 dNIHSS score,7 dthrombolysis and 3 months thrombolysis and thrombolysis 3 months improved Rankin score (mRs).Results There was no significant difference in baseline characteristics between the two groups (P＞0.05).Compared with the consultation group,the DNT[(69.77±11.66)min vs (80.12±15.49) min,t=5.745,P ＜ 0.01] of emergency thrombolytic group was significantly shortened,and the good score[39(39.4％) vs 21(25.3％),x2=4.272,P=0.039] at 3 months after treatment was significantly higher (P＜0.05);Treatment of 24 h intracranial hemorrhage conversion rate[12(12.12％) vs 5(6.02％),x2=1.982,P=0.159]、Treatment 7d mortality rate [10(10.10％) vs 6(7.22％),x2=0.464,P=0.496],3 months mortality rate [14(14.14％) vs 11 (13.25％),x2=0.030,P=0.862]、There was no significant difference in the 24h effective rate [57(57.6％) vs 53(63.8％),x2=0.745,P=0.388] and 7d effective rate [50(50.5％) vs 46(55.4％),x2=0.438,P0.508] after treatment (P＞0.05).Conclusions The emergency thrombolytic model can shorten the DNT of rt-PA intravenous thrombolysis in patients with AIS.The safety and efficacy of DNT are not different from the neurological consultation mode,and can improve the good prognosis rate.
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Objective@#To analyz the current situation of the diagnosis, treatment and prevention of methylmalonic acidemia, the phenotypes, biochemical features and genotypes of the patients in the mainland of China, were investigated.@*Methods@#Tottally 1 003 patients of methylmalonic acidemia from 26 provinces and municipalities of the mainland of China were enrolled. The clinical data, biochemical features and gene mutations were studied. Blood aminoacids and acylcarnitines, urine organic acids, and plasma total homocysteine were determined for the biochemical diagnosis. Gene analyses were performed for the genetic study of 661 patients. The patients were treated with individual intervention and long-term follow up. Prenatal diagnoses were carried out for 165 fetuses of the families.@*Results@#Among 1 003 patients (580 boys and 423 girls), 296 cases (29.5%) had isolated methylmalonic acidemia; 707 cases (70.5%) had combined homocysteinemia; 59 patients (5.9%) were detected by newborn screening; 944 patients (94.1%) had the onset at the ages from several minutes after birth to 25 years and diagnosed at 3 days to 25 years of age. The main clinical presentations were psychomotor retardation and metabolic crisis. Multi-organ damage, including hematological abnormalities, pulmonary hypertension, kidney damage, were found. MMACHC, MUT, MMAA, MMAB, HCFC1, SUCLG1, SUCLA2 mutations were found in 631 patients (96.6%) out of 661 patients who accepted gene analysis. MMACHC mutations were detected in 460 patients (94.7%) out of 486 cases of methylmalonic acidemia combined with homocysteinemia. MUT mutations were found in 158 (90.3%) out of 169 cases of isolated methylmalonic acidemia. The development of 59 patients detected by newborn screening were normal; 918 cases (97.2%) were diagnosed after onset accepted the treatment. Forty-five of them completely recovered with normal development. Twenty-six patients (2.7%) died; 873 (92.5%) patients had mild to severe psychomotor retardation. Methylmalonic acidemia were found in 35 out of 165 fetuses by metabolites assay of amniotic fluid and amniocytes gene analysis.@*Conclusion@#Combined methylmalonic acidemia and homocysteinemia is the common type of methylmalonic acidemia in the mainland of China. CblC defect due to MMACHC mutations is the most common type of methylmalonic acidemia combined with homocysteinemia. MUT gene mutations are frequent in the patients with isolated methylmalonic acidemia. Newborn screening is key for the early diagnosis and the better outcome. Combined diagnosis of biochemical assays and gene analysis are reliable for the prenatal diagnosis of methylmalonic acidemia.
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Objective To investigate the clinical and molecular genetic characteristics of hypermethioninemia caused by methionine adenosyltransferase deficiency. Methods The clinical data and related gene analysis of hypermethioninemia caused by methionine adenosyltransferase deficiency in 3 children were retrospectively analyzed. The core pedigree analysis was carried out. Results Three children (2 boys and 1 girl) aged from 5 months to 3 years, were from 3 unrelated families. All of them had no family history. One case was found in neonatal screening. One case was onset with pathological jaundice at 1 month old. Another case was found due to tremor and growth retardation at 2 years old. Blood amino acid ester acyl carnitine spectrum analysis showed that all of them had significantly elevated levels of methionine at 134.50-790.67 μmol/L. All children had MAT1A mutation in methionine adenosyltransferase gene. One case was heterozygous mutations with third exon c.274T>C and seventh exon c.895C>T mutation; one case had sixth exon c.757G>A homozygous mutation; and another case had seventh exon c.791G>A homozygous mutation. The core pedigree analysis showed that the mutations were from theirs parents respectively. Conclusions For children with neurologic impairment, methionine metabolic disorders should be considered. Blood amino acids and gene analysis are important methods for confirmation of the diagnosis. Neonatal screening is an effective way to detect this disease.
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Objective To understand the relationship between AOX1,IRF4 gene methylation status in peripheral blood leukocyte DNA,as well as its interaction with environmental factors,and the risk of breast cancer.Methods A case-control study was conducted among 401 breast cancer patients and 555 cancer-free controls selected from 2010 to 2014.Methylation sensitive-high resolution melting curve analysis was used to detect the methylation status of AOX1 and IRF4.The multiplication interaction effect between genes' methylation and environmental factors on the risk of breast cancer was analyzed by using unconditional logistic regression,and Excel software was used to analyze the additive interaction effect.Results Individuals without AOX1 methylation had a 1.37-fold (95％ CI:1.02-1.84) higher breast cancer risk compared to individuals with AOX1 methylation.AOX1 methylation interacted with fungi intake (OR=2.06,95％ CI:1.12-3.79) and physical activity (OR=2.18,95％CI:1.16-4.09) synergistically,on the risk for breast cancer,but no additive interaction effects were observed.Non-methylation of IRF4 could increase the risk for breast cancer,with statistical significance (OR=1.71,95％CI:0.99-7.43).Neither multiplication nor additive interactions were observed between IRF4 methylation and environmental factors.Conclusion Non-methylation of AOX1 and IRF4 were a risk factors for breast cancer.
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Objective To understand the relationship between AOX1,IRF4 gene methylation status in peripheral blood leukocyte DNA,as well as its interaction with environmental factors,and the risk of breast cancer.Methods A case-control study was conducted among 401 breast cancer patients and 555 cancer-free controls selected from 2010 to 2014.Methylation sensitive-high resolution melting curve analysis was used to detect the methylation status of AOX1 and IRF4.The multiplication interaction effect between genes' methylation and environmental factors on the risk of breast cancer was analyzed by using unconditional logistic regression,and Excel software was used to analyze the additive interaction effect.Results Individuals without AOX1 methylation had a 1.37-fold (95％ CI:1.02-1.84) higher breast cancer risk compared to individuals with AOX1 methylation.AOX1 methylation interacted with fungi intake (OR=2.06,95％ CI:1.12-3.79) and physical activity (OR=2.18,95％CI:1.16-4.09) synergistically,on the risk for breast cancer,but no additive interaction effects were observed.Non-methylation of IRF4 could increase the risk for breast cancer,with statistical significance (OR=1.71,95％CI:0.99-7.43).Neither multiplication nor additive interactions were observed between IRF4 methylation and environmental factors.Conclusion Non-methylation of AOX1 and IRF4 were a risk factors for breast cancer.
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Objective To explore the clinical features and genetic etiology of children with cystinuria with onset of kidney stone. Methods The clinical data of 3 children with cystinuria with onset of kidney stone and the gene analysis results of SLC3A1 and SLC7A9 by PCR sequencing were retrospectively analyzed.Results Three male children were from three unrelated families, kidney stone were presented in 2 cases at 1 year old and 1 case at 14 years old. The blood amino acid spectrum was normal in all 3 cases, while the free carnitine were decreased. The urinary amino acid spectrum indicated that cystine, ornithine, arginine,and threonine increased.Gene analysis confirmed that 1 case had homozygous mutations of SLC7A9 gene c.325G>A, and his parents were carriers of c.325G>A heterozygous mutation;other 2 cases had heterozygous mutations of SLC3A1 gene, c.1365delG and c.1113C>A heterozygous mutation in one case, and c.1897_1898insTA and c.1093C>T heterozygous mutation in one case, and their parents were heterozygous mutation carriers. After treatment with potassium citrate and L-carnitine, the conditions were improved in all cases. Conclusions Inherited metabolic disease should be considered for children with kidney stone. Urine amino acid analysis and gene detection are important methods for the diagnosis of cystinuria.
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Objective To investigate the clinical features,karyotype,and the prenatal diagnosis for his sibling of a Chinese patient with rare ring chromosome 20 syndrome induced intractable epilepsy.Methods The clinical data of the patient diagnosed in Peking University People's Hospital were collected.The clinical manifestations,chromosome karyotype were summarized.Results The proband,a boy,started to show intermittent tonic seizures or atypical absence seizures and psychomotor retardation from the age of 11 months.Several anti-epilepsy drugs and globulin had been tried without effect.Common karyotype analysis and epilepsy-related genes analysis revealed no abnormality.However,abnormal karyotype 46,XY,r(20)(p13q13.3) in his peripheral blood lymphocytes was found by high resolution chromosome karyotype analysis with 550 G-banding,and the diagnosis of ring chromosome 20 syndrome,type Ⅱ was confirmed.The mother of the patient underwent amniocentesis at the midterm of the second pregnancy.The cultured amniocytes karyotypes were normal.The second child(a boy) of the family was 1 year old without epilepsy and the psychomotor development was normal.Conclusions Ring chromosome 20 syndrome is a rare human chromosome abnormality.The syndrome is associated with epileptic seizures,behavior disorders and mental retardation.Since karyotype testing is not a routine investigation for the patient with epilepsy,the diagnosis of ring chromosome 20 syndrome is usually delayed or misdiagnosed.The karyotype analysis should be considered for the etiological study of the patients with intractable epilepsy with unknown origin.
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Objective To explore the diagnosis and treatment of a rare case of methylmalonic aciduria combined with congenital adrenal hyperplasia. Methods The clinical and laboratory data of the first case of methylmalonyl CoA mutase deifcient methylmalonic aciduria combined with 21-hydroxylase deifciency in China were analyzed. Results The male patient with age of onset at 3 months presented with feeding dififculty, diarrhea, metabolic acidosis, and psychomotor retardation after polio vaccination or high protein diet. At one year and 8 months of age, methylmalonic aciduria was diagnosed, and the patient was clinically improved after treatment. At 5 years of age, precocious puberty was noticed, and virilizing form of 21-Hydroxylase deifciency was diagnosed. Genetic testing conifrmed 2 known mutations in MUT gene (c.866G?>?C, c.2179C?>?T) and 2 known mutations in CYP21A2 gene (c.188A?>?T, c.518T?>?A). Conclusions The clinical manifestations of inherited metabolic disorders and endocrine diseases are complex and it is rare that multiple disorders occurred simultaneously in one patient. This male patient has two rare diseases, methylmalonic aciduria and 21-hydroxylase deifciency.
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Objective To explore the clinical and genetic features in the pedigree of Cb1X type X-linked methylmalonic aciduria. Methods Clinical data of one child with X-linked methylmalonic aciduria diagnosed by blood and urine analysis were analyzed retrospectively. Targeted next-generation sequencing has been performed to detect the mutation of methylmalonic aciduria-related genes. Results The boy started presenting with seizures and severe mental retardation at 2 months of age. At 5 months of age, he had the manifestations of seizures, severe mental retardation, increased methylmalonic acid in urinary, increased propionylcarnitine in blood and increased plasma homocysteine, and met the requirements for the diagnosis of methylmalonic aciduria complicated with hyperhomocysteinemia. No mutation was detected in his MMA-related autosomal genes. However, a hemizygote mutation c.344C?>?T (p.Ala115Val) was identiifed in exon 3 of HCFC1 in X chromosome, which conifrmed the CblX type methylmalonic aciduria. His parents were healthy. His elder brother also manifested severe psychomotor retardation with intractable epilepsy, and died at 6 months of age with unknown cause. His mother carried the same mutation and had slightly elevated urine methylmalonic acid and plasma total homocysteine. His father did not carry the mutation. Conclusion A pedigree of a rare Cb1X type X-linked methylmalonic acidemia is ifrstly diagnosed in China by the new generation sequencing technology.
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Humans typically have 22 pairs of autosomal chromosomes in cells,and a pair of sex chromosomes.Some individuals have an extra,autosomal chromosome called a small supernumerary marker chromosome (sSMC).sSMC is a structurally abnormal chromosome fragment.The fragments are too small and no-specific banding pattern to be identified by conventional banding cytogenetic analysis.Array-based comparative genomic hybridization (aCGH),fluorescence in situ hybridization (FISH) or other molecular biological methods are necessary for the diagnosis.This article summarized the karyotype,pathogenesis,and the clinical manifestations of the sSMC-related chromosome 18p abnormalities.The patients with sSMC usually presented with abnormal chromosome syndrome.Some syndromes are relative common,such as Pallister-Killian syndrome,isochromosome 18p syndrome,Cat eye syndromes or Emanuel syndrome.sSMC is considered to be the frequent cause of mental retardation.The patients have no specific symptoms.With the progress of molecular cytogenetics,more sSMC has been identified.Genetic counseling and prenatal diagnosis are important to prevent sSMC.Molecular cytogenetic techniques are necessary to the diagnosis.
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Objective To use the genetic diagnosis technique to perform the gene detection in the patients with thalassemia for understanding the main gene mutation types and their gene frequencies .Methods Totally 5 500 outpatients and individuals un‐dergoing physical examination in the hematology department of the Huizhou Municipal Central People′s Hospital from January 2010 to October 2014 were taken as the research subjects .The GAP‐PCR and membrane reverse hypridition technology were adopted to conduct the gene analysis of α‐andβ‐thalassemia .Results A total of 1 604 cases ofα‐globin gene change were detected ,accounting for 29 .16% of the total detected subjects ;1 096 cases ofβ‐globin gene change were detected ,accounting for 19 .93% of the total de‐tected subjects ;119 cases of αβ‐complex thalassemia were detected .Conclusion The gene screening of α‐ and β‐ thalassemia pro‐vides the valuable basic data for conducting the marital and fertility instructions .
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Objective To explore the diagnosis of cystinosis.Methods The clinical and biochemical information, and gene detection results in a child with cystinosis was retrospective analyzed.Results Four-year-old female presented with photophobia and corneal crystal was found by ophthalmic examination at 2 years old, bilateral kidney stone was found, accompanied by development delay and rickets at 3 years old. Gas chromatography analysis in urine showed that a variety of amino acids were increased, and urine sugar and urinary micro-protein were also increased, which were in accordance with fanconi syndrome. The blood free carnitine was decreased, ester acyl carnitine spectrum was normal, and multi-amino acids such as lysine, valine and arginine were decreased. Gene analysis showed a homozygous mutation of c.696C>G (p.323 N>K) inCTNS gene, which was a known mutation. Both her parents were carrier of heterozygous mutation of c.696C>G inCTNS gene.Conclusion Child with kidney stone, renal damage, combined by multi-system damage such as eyes, bone, and thyroid should be paid attention to identify the cystinosis.
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<p><b>OBJECTIVE</b>Argininemia is a rare disorder of urea cycle defect. The clinical manifestations of this disorder are similar to those of cerebral palsy so that the diagnosis is usually much delayed. This study aimed to investigate the phenotypes and genotypes of seven Chinese patients suffering from argininemia.</p><p><b>METHOD</b>Three boys and four girls with spastic tetraplegia were diagnosed as argininemia by blood aminoacids analysis and ARG1 gene study. Patients were given a protein-restricted diet, citrulline, sodium benzoate, and other treatment intervention. The mother of Patient 5 and 6 accepted genetic counseling and underwent prenatal diagnosis by amniocentesis.</p><p><b>RESULT</b>Seven patients presented with progressive spastic tetraplegia and poor physical growth from the age of 1 month to 4 years. Argininemia was found at the age of 1 year and 10 months to 12 years. Five patients had mental retardations. Three had seizures. Their blood arginine elevated (86.66 to 349.83 µmol/L, normal controls 5 to 25 µmol/L). Liver dysfunction was found in six patients. Five patients had elevated blood ammonia levels. In four patients, cerebral atrophy was observed by cranial magnetic resonance imaging. Nine mutations in the ARG1 gene were identified from 7 patients. Only two mutations, c.703G > A in exon 7 and c.32T > C in exon 1 had been reported. c.34G > T, c.53G > A, c.67delG, c.232dupG, c.374C > T, c.539G > C and c.646-649delCTCA, were novel mutations of ARG1. A homozygous mutation c.703G > A was found in the amniocytes of Patient 5's mother, indicating that the fetus was affected by argininemia. Induced abortion was performed. c.53G > A from Patient 6 was not found in the amniocytes of her mother, indicating that the fetus was not affected by hepatocyte arginase deficiency. The result was confirmed by postnatal mutation analysis of cord blood and the normal blood arginine of the newborn.</p><p><b>CONCLUSION</b>Argininemia is one of the few treatable causes of pediatric spastic paralysis. In this study, seven Chinese patients with spastic tetraplegia were detected by blood aminoacids analysis and confirmed by molecular analysis. Seven novel mutations on ARG1 gene were identified. Prenatal diagnosis of the fetus of a family was performed by amniocytes ARG1 gene analysis.</p>
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Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Pregnancy , Abortion, Induced , Amniocentesis , Arginase , Arginine , Blood , Asian People , DNA Mutational Analysis , Diet, Protein-Restricted , Exons , Fetus , Genotype , Homozygote , Hyperammonemia , Diagnosis , Hyperargininemia , Diagnosis , Mutation , Phenotype , Prenatal Diagnosis , Quadriplegia , Diagnosis , SeizuresABSTRACT
Objective To investigate the clinical,biochemical and genetic findings in patients with isolated methylmalonic aciduria. Methods From January 2001 to December 2014,a total of 126 patients with isolated methyl-malonic aciduria from Peking University First Hospital were enrolled in this study. In 60 patients,gene analysis was per-formed. The clinical characteristics,laboratory findings,treatment and outcomes were retrospectively analyzed. Results Among the 126 patients,only 3 cases(2. 4% )were detected through newborn screening and treated with dietary in-tervention,cobalamin and L - camitine. The age at onset of 123 cases(97. 6% )varied from a few hours after birth to 7 years and 11 months old. The common presentations were recurrent vomiting,mental retardation,poor feeding,lethargy, respiratory distress,coma,seizures,cutaneous lesion and jaundice with 11 patients(8. 73% )dead. Abnormal family his-tory was found in 27(21. 4% )patients. Metabolic acidosis and anemia were frequent laboratory findings. Basal ganglia damage and white matter changes were observed in most patients. Sixty patients got genetic analysis,and 58 cases of them had MUT gene mutations. One case had MMAA defect. One case had MMAB defect. In MUT gene,12 novel muta-tions were identified. After treatment,mild to severe psychomotor retardation was observed in 112 patients with isolated methylmalonic aciduria. Conclusions The clinical manifestation of patients with isolated methylmalonic aciduria is complex,and prone to appear metabolic crisis. MUT defect is the main cause. Early metabolic investigation is very im-portant to reach diagnosis. Newborn screening,early diagnosis and adequate therapy are key points to reduce the morta-lity and handicap.
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<p><b>OBJECTIVE</b>We report the first case of acute encephalopathy induced by vaccination in an infant with methylmalonic aciduria cblA in China.</p><p><b>METHOD</b>The clinical presentation, blood acylcarnitines analysis, urine organic acids analysis and gene studies of the patient were summarized.</p><p><b>RESULT</b>The proband, a boy, was admitted at the age of 15 months because of recurrent vomiting, acidosis and development delay for 8 months. The previously healthy boy presented vomiting and coma just one hour after hepatitis B vaccination at the age of seven months. Moderate dehydration, electrolyte disturbance and metabolic acidosis had been found. Although his acute metabolic crisis had been corrected soon after intravenous transfusion, psychomotor retardation and recurrent vomiting had been observed. When he was 15 months old, vomiting and lethargy occurred again 3 hours after DTaP vaccination. He was weakened as the illness became worse and got coma with dyspnea 7 days later. He was hospitalized with the suspected diagnosis of viral encephalitis. Blood acylcarnitines analysis, urine organic acids analysis and gene study had been performed for the etiologic investigation.His blood propionylcarnitine (16.3 µmol/L vs. normal range 1.0-5.0 µmol/L) and propionylcarnitine/free carnitine ratio (0.27 vs. normal range 0.03 to 0.25) increased. Markedly elevated urinary methylmalonic acid (388.21 mmol/mol creatinine vs. normal range 0.2 to 3.6 mmol/mol creatinine) and normal plasma total homocysteine supported the diagnosis of isolated methylmalonic aciduria. Two mutations, c.650 T>A (p.L217X) and c.742 C>T (p.Q248X), were identified in his MMAA gene, confirmed the diagnosis of cblA. Each parent carried one of the two mutations. Progressive clinical and biochemical improvement has been observed after hydroxylcobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine. He is currently 2 years and 7 months old with normal development and general condition.</p><p><b>CONCLUSION</b>A boy with cblA was firstly detected after the acute encephalopathy induced by vaccination in China. It is important to pay more attention to the patients with metabolic crisis or organ damage after vaccination. Metabolic studies are keys to the diagnosis of potential diseases and improve the outcome.</p>
Subject(s)
Humans , Infant , Male , Amino Acid Metabolism, Inborn Errors , Brain Diseases , Carnitine , Diet, Protein-Restricted , Hepatitis B Vaccines , Methylmalonic Acid , Urine , Mutation , Vaccination , Vitamin B Complex , VomitingABSTRACT
To be on the alert on infants with esophageal foreign body, and to pay more attention to the button battery esophageal foreign body, the clinical data of a 12-month-old infant with button battery esophageal foreign body, which was missed diagnosis for up to 4 months, is analyzed. And the related literature is reviewed. An esophagoscopy was carried out to remove the foreign body. A favorable outcome was achieved. When the infants have unexplained gastrointestinal symptoms, we should consider the possibility of an esophageal foreign body. We should pay attention to the button battery due to its highly corrosive to the esophagus. Timely diagnosis, reasonable operation are the keys to cure.