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Yanling Yang - One of the best experts on this subject based on the ideXlab platform.
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five novel suclg1 mutations in three chinese patients with succinate coa ligase deficiency noticed by mild Methylmalonic aciduria
Brain & Development, 2016Co-Authors: Xiyuan Li, Jinqing Song, Yuan Ding, Yanling YangAbstract:Abstract Objective Methylmalonic aciduria is the most common organic aciduria in mainland China. Succinate-CoA ligase deficiency causes encephalomyopathy with mitochondrial DNA depletion and mild Methylmalonic aciduria. Patients usually present with severe encephalomyopathy, infantile lactic acidosis, which can be fatal, and mild Methylmalonic aciduria. Patients and methods Three Chinese patients (two boys and one girl) were hospitalized because of severe encephalomyopathy between 7 and 9 months. They presented with severe psychomotor retardation, hypotonia, dystonia, athetoid movements, seizures, feeding problems and failure to thrive. Mild elevated urine Methylmalonic acid and blood propionylcarnitine indicated Methylmalonic aciduria. Gene capture and high-throughput genomic sequencing was carried out. Results Five novel mutations in SUCLG1 were identified in these patients: c.550G>A (p.G184S) in exon 5, c.751C>T (p.G251S) in exon 7, c.809A>C (p.L270W) in exon 7, c.961C>G (p.A321P) in exon 8 and c.826-2A>G (Splicing) in exon 9. Significant depletion of mtDNA was not observed in the peripheral leukocytes of the three patients in spite of mild decreasing of mitochondrial respiratory chain complex I in two patients and complex V in one patient. After treatment with cobalamin, calcium folinate, l -carnitine, vitamin B1, C, and coenzyme Q10, and nutrition intervention, the patients improved. Conclusions Succinate-CoA ligase deficiency due to SUCLG1 mutations is a rare cause of Methylmalonic aciduria. Biochemical and gene studies are keys for the differential diagnoses. Three Chinese patients with mild Methylmalonic aciduria were genetically diagnosed using high-throughput genomic sequencing. Five novel pathogenic mutations in SUCLG1 were identified.
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first chinese case of successful pregnancy with combined Methylmalonic aciduria and homocystinuria cblc type
Brain & Development, 2015Co-Authors: Y Liu, Jinqing Song, Yuan Ding, Qiao Wang, Yanling YangAbstract:Abstract Objective: Combined Methylmalonic aciduria (MMA) and homocystinuria, cblC type, is the most common MMA in Mainland China. Its clinical spectrum varies from severe neonatal-onset forms with brain injury and high mortality to milder forms with late onset. Timely diagnosis and adequate treatment greatly improve the prognosis. In the past 15 years, many Chinese patients with this condition have achieved favorable treatment outcomes, and some of them have reached childbearing age. Here, we report the first case of Chinese woman with cblC undergoing a successful pregnancy and delivering a healthy boy. Methods: A patient of late-onset cblC, who achieved successful pregnancy and delivery of a healthy boy, was enrolled in our studies. The patient and her disease characteristics were analyzed, including age at onset, age at diagnosis, clinical presentation, clinical classification, family history, laboratory findings and MMACHC gene mutation. Results: Our patient presented mild neurological symptoms at the age of 15 years. She had the compound heterozygous mutations, c.315C>G and c.482G>A, on the MMACHC gene. After long-term treatment with cobalamin, calcium folinate, l-carnitine and betaine, along with normal diet, she recovered completely. At age 23, she visited us for genetic counseling and fetal evaluation at 15 weeks of gestation. Her general condition and the fetal growth were normal. At 20 weeks of gestation, intramuscular cobalamin was changed to pure hydroxocobalamin (1 mg, every other day) because of markedly elevated urine MMA and plasma total homocysteine. In addition, the dosages of l-carnitine (1 g, p.o., tds), folic acid (5 mg, p.o., tds) and betaine (1 g, p.o., tds) were increased. Protein intake was not restricted. Conclusions: This is the first report of a Chinese woman with cblC, undergoing a successful pregnancy and delivering a healthy baby at term. The favorable outcome of the patient and her fetus should owe much to the mild phenotype of her disease.
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abnormal findings during newborn period of 160 patients with early onset Methylmalonic aciduria
Chinese journal of pediatrics, 2012Co-Authors: Yupeng Liu, Jinqing Song, Yuan Ding, Qiao Wang, Yu Huang, Yanling YangAbstract:Objective Methylmalonic aciduria is the most common disorder of organic acidurias in the mainland of China. It is also the one of treatable metabolic disorders. The clinical spectrum of the patients varies from severe neonatal-onset forms with neonatal brain injury and high mortality to milder forms with adult-onset. The clinical manifestations of neonates with Methylmalonic aciduria are non-specific. Early diagnosis and adequate treatment contribute a lot to improving the prognosis of the patients. In this study, the abnormal clinical and laboratory findings in neonatal period of 160 Chinese patients with early-onset Methylmalonic aciduria were investigated. Method From 1996 to 2011, a total of 398 patients with Methylmalonic aciduria were diagnosed in our hospital; 286 (71.9%) patients had early-onset before 1 year of age. Among 286 patients, 160 (55.9%) presented symptoms in neonatal period. Their urine organic acids were analyzed by gas chromatography-mass spectrometry. Blood amino acids and acylcarnitine profiles were determined by liquid chromatography tandem mass spectrometry. Serum and urine total homocysteine were measured using a fluorescence polarization immunoassay. In some patients, gene analysis was performed. Based on the disease types and general condition, individual dietary and medical interventions were started soon after diagnosis. Result Out of the 160 patients, 131 (81.9%) had combined Methylmalonic aciduria and homocysteinemia. Isolated Methylmalonic aciduria was found in 29 cases (18.1%). The common presentations in neonatal period were feeding difficulty, seizures, lethargy and dyspnea. Megaloblastic anemia, liver dysfunction, hyperammonemia and metabolic acidosis were the frequent findings in the routine laboratory test. The most common initial clinical diagnosis was suspected hypoxic-ischemic encephalopathy. Even in 36 cases with abnormal family history, only 3 patients were admitted with suspected inborn errors of metabolism. Five cases (3.1%) were diagnosed by postmortem metabolic examination; 7 cases (4.4%) were detected by newborn screening. In 148 cases (92.5%), the diagnosis was much delayed to the age of one month to 8 years and 5 months (mean 13 months). Methylmalonic aciduria combined with homocysteinemia (MMACHC) gene analyses were performed in 31 cases with combined Methylmalonic aciduria. CblC defect was confirmed. The patients with isolated Methylmalonic aciduria were treated with protein-restricted diet, cobalamin and L-carnitine. The patients of Methylmalonic aciduria combined with homocysteinemia were treated with cobalamin, L-carnitine, calcium folinate, betaine and common diet. Seven patients died without treatment. Clinical improvement was observed in 153 patients. Only 2 patients detected by newborn screening had normal mental and physical development. Mild to severe psychomotor retardation was observed in 151 cases. Conclusion High mortality and disability rates were observed in the patients with early-onset Methylmalonic aciduria. Combined Methylmalonic aciduria and homocysteinemia is the common type of Methylmalonic aciduria. The clinical manifestation in neonatal period of the patients with early-onset Methylmalonic aciduria is complex. Feeding difficulty, seizures, lethargy and dyspnea are the common symptoms in neonatal period of the patients. Megaloblastic anemia, liver dysfunction, hyperammonemia and metabolic acidosis were the frequent laboratory findings. Key words: Organic acidurias; Methylmalonic aciduria; Hyperhomocysteinemia; Neonatal
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mutation spectrum of mmachc in chinese patients with combined Methylmalonic aciduria and homocystinuria
Journal of Human Genetics, 2010Co-Authors: Yanling Yang, Yingchen Chang, Szuhui Chiang, Yu Qi, Kwangjen HsiaoAbstract:Mutation spectrum of MMACHC in Chinese patients with combined Methylmalonic aciduria and homocystinuria
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mutation spectrum of mmachc in chinese patients with combined Methylmalonic aciduria and homocystinuria
Journal of Human Genetics, 2010Co-Authors: Mei Ying Liu, Yingchen Chang, Szuhui Chiang, Kwangjen Hsiao, Yanling Yang, Shuanpei Lin, Lian Shu Han, Tze Tze LiuAbstract:The cblC type of combined Methylmalonic aciduria (MMA) and homocystinuria (HC) is the most common inborn error of vitamin B(12) metabolism and is caused by mutations in the MMACHC gene. To elucidate the spectrum of mutations that causes combined MMA and HC in Chinese patients, the MMACHC gene was sequenced in 79 unrelated Chinese patients. Sequence analysis identified 98.1% of disease alleles and found that all patients had at least one MMACHC mutation. A total of 24 mutations were identified. Out of the 24 mutations identified, 9 were novel ones, including missense mutations (c.365A>T and c.452A>G), nonsense mutations (c.315C>G and c.615C>A), deletions (c.99delA and c.277-3_c.303del30), duplications (c.248dupT and c.626dupT) and an insertion (c.445_446insA). The c.609G>A, c.658_660delAAG, c.482G>A, c.394C>T and c.80A>G mutations were the most common mutations and accounted for 80% of disease alleles. Haplotype analysis suggests that the spread of the c.80A>G, c.609G>A and c.658_660delAAG mutations in Chinese patients were caused by a founder effect. The results indicate that defects occurring in the MMACHC gene are the major cause of this disease in Chinese patients with combined MMA and HC, and direct mutation analysis can therefore be used as a rapid confirmatory diagnosis among these Chinese patients.
Yang Yanling - One of the best experts on this subject based on the ideXlab platform.
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Five novel SUCLG1 mutations in three Chinese patients with succinate-CoA ligase deficiency noticed by mild Methylmalonic aciduria
BRAIN & DEVELOPMENT, 2016Co-Authors: Liu Yupeng, Ding Yuan, Song Jinqing, Li Xiyuan, Wang Qiao, Yang YanlingAbstract:Objective: Methylmalonic aciduria is the most common organic aciduria in mainland China. Succinate-CoA ligase deficiency causes encephalomyopathy with mitochondrial DNA depletion and mild Methylmalonic aciduria. Patients usually present with severe encephalomyopathy, infantile lactic acidosis, which can be fatal, and mild Methylmalonic aciduria. Patients and methods: Three Chinese patients (two boys and one girl) were hospitalized because of severe encephalomyopathy between 7 and 9 months. They presented with severe psychomotor retardation, hypotonia, dystonia, athetoid movements, seizures, feeding problems and failure to thrive. Mild elevated urine Methylmalonic acid and blood propionylcamitine indicated Methylmalonic aciduria. Gene capture and high-throughput genomic sequencing was carried out. Results: Five novel mutations in SUCLG1 were identified in these patients: c.550G>A (p.G184S) in exon 5, c.751C>T (p.G251S) in exon 7, c.809A>C (p.L270W) in exon 7, c.961C>G (p.A321P) in exon 8 and c.826-2A>G (Splicing) in exon 9 Significant depletion of mtDNA was not observed in the peripheral leukocytes of the three patients in spite of mild decreasing of mitochondrial respiratory chain complex I in two patients and complex V in one patient. After treatment with cobalamin, calcium folinate, L-carnitine, vitamin B1, C, and coenzyme Q10, and nutrition intervention, the patients improved. Conclusions: Succinate-CoA ligase deficiency due to SUCLG1 mutations is a rare cause of Methylmalonic aciduria. Biochemical and gene studies are keys for the differential diagnoses. Three Chinese patients with mild Methylmalonic aciduria were genetically diagnosed using high-throughput genomic sequencing. Five novel pathogenic mutations in SUCLG1 were identified. (c) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.National Nature Science Foundation of China [81471097]; Ministry of Science and Technology [2012BAI09B04]SCI(E)PubMedARTICLEorganic.acid@126.com161-673
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Acute encephalopathy induced by vaccination in an infant with Methylmalonic aciduria cblA
zhonghua er ke za zhi chinese journal of pediatrics, 2015Co-Authors: Liu Yupeng, Wu Tongfei, Wang Haijun, Ding Yuan, Song Jinqing, Li Xiyuan, Zhang Yao, Wang Qiao, Yang YanlingAbstract:We report the first case of acute encephalopathy induced by vaccination in an infant with Methylmalonic aciduria cblA in China.The clinical presentation, blood acylcarnitines analysis, urine organic acids analysis and gene studies of the patient were summarized.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.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.PubMed0162-55
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First Chinese case of successful pregnancy with combined Methylmalonic aciduria and homocystinuria, cblC type
brain development, 2015Co-Authors: Liu Yupeng, Ding Yuan, Song Jinqing, Li Xiyuan, Wang Qiao, Yang YanlingAbstract:Objective: Combined Methylmalonic aciduria (MMA) and homocystinuria, cblC type, is the most common MMA in Mainland China. Its clinical spectrum varies from severe neonatal-onset forms, with brain injury and high mortality to milder forms with late onset. Timely diagnosis and adequate treatment greatly improve the prognosis. In the past 15 years, many Chinese patients with this condition have achieved favorable treatment outcomes, and some of them have reached childbearing age. Here, we report the first case of Chinese woman with cblC undergoing a successful pregnancy and delivering a healthy boy. Methods: A patient of late-onset cblC, who achieved successful pregnancy and delivery of a healthy boy, was enrolled in our studies. The patient and her disease characteristics were analyzed, including age at onset, age at diagnosis, clinical presentation, clinical classification, family history, laboratory findings and MMACHC gene mutation. Results: Our patient presented mild neurological symptoms at the age of 15 years. She had the compound heterozygous mutations, c.315C>G and c.482G>A, on the MMACHC gene. After long-term treatment with cobalamin, calcium folinate, 1-carnitine and betaine, along with normal diet, she recovered completely. At age 23, she visited us for genetic counseling and fetal evaluation at 15 weeks of gestation. Her general condition and the fetal growth were normal. At 20 weeks of gestation, intramuscular cobalamin was changed to pure hydroxocobalamin (1 mg, every other day) because of markedly elevated urine MMA and plasma total homocysteine. In addition, the dosages of 1-carnitine (1 g, p.o., tds), folic acid (5 mg, p.o., tds) and betaine (1 g, p.o., tds) were increased. Protein intake was not restricted. Conclusions: This is the first report of a Chinese woman with cblC, undergoing a successful pregnancy and delivering a healthy baby at term. The favorable outcome of the patient and her fetus should owe much to the mild phenotype of her disease. (C) 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.Clinical NeurologySCI(E)PubMed0ARTICLEorganic.acid@126.com3286-2913
Matthias R Baumgartner - One of the best experts on this subject based on the ideXlab platform.
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protein destabilization and loss of protein protein interaction are fundamental mechanisms in cbla type Methylmalonic aciduria
Human Mutation, 2017Co-Authors: Tanja Plessl, Celine Burer, Seraina Lutz, Matthias R Baumgartner, Sean D FroeseAbstract:Mutations in the human MMAA gene cause the metabolic disorder cblA-type Methylmalonic aciduria (MMA), although knowledge of the mechanism of dysfunction remains lacking. MMAA regulates the incorporation of the cofactor adenosylcobalamin (AdoCbl), generated from the MMAB adenosyltransferase, into the destination enzyme methylmalonyl-CoA mutase (MUT). This function of MMAA depends on its GTPase activity, which is stimulated by an interaction with MUT. Here, we present 67 new patients with cblA-type MMA, identifying 19 novel mutations. We biochemically investigated how missense mutations in MMAA in 22 patients lead to disease. About a third confer instability to the recombinant protein in bacterial and human expression systems. All 15 purified mutant proteins demonstrated wild-type like intrinsic GTPase activity and only one (p.Asp292Val), where the mutation is in the GTP binding domain, revealed decreased GTP binding. However, all mutations strongly decreased functional association with MUT by reducing GTPase activity stimulation upon incubation with MUT, while nine mutant proteins additionally lost the ability to physically bind MUT. Finally, all mutations interfered with gating the transfer of AdoCbl from MMAB to MUT. This work suggests loss of functional interaction between MMAA and MUT as a disease-causing mechanism that impacts processing and assembly of a cofactor to its destination enzyme.
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molecular genetic characterization of 151 mut type Methylmalonic aciduria patients and identification of 41 novel mutations in mut
Human Mutation, 2016Co-Authors: Patrick Forny, Seraina Lutz, Matthias R Baumgartner, Sean D Froese, Annesophie Schnellmann, Celine Buerer, Brian FowlerAbstract:Isolated Methylmalonic aciduria (MMA) is an autosomal-recessive disorder of propionate metabolism that is most commonly caused by mutations in the methylmalonyl-CoA mutase (MUT) gene (mut-type MMA). We investigated a cohort of 151 patients, classifying 114 patients as mut0 and 32 as mut− (five not defined). As per the definition, mut− patients showed a higher propionate incorporation ratio in vitro, which was correlated to a considerably later age of onset compared with mut0 patients. In all patients, we found a total of 110 different mutations, of which 41 were novel. While the missense alleles p.Asn219Tyr, p.Arg369His, and p.Arg694Trp recurred in >10 alleles, 47 mutations were identified only once, suggesting many patients carry private mutations. Deficient alleles in the mut− subclass were almost exclusively caused by missense mutations, found disproportionately in the C-terminal cofactor binding domain. On the contrary, only half of the mut0 mutations were of the missense type. Western blot analysis revealed reduced MUT protein for all 34 cell lines (27 mut0, seven mut−) tested, suggesting protein instability as a major mechanism of deficiency in mut-type MMA. This large-scale evaluation helps to characterize the landscape of MUT mutations and their relationship to dysfunction and disease.
Sean D Froese - One of the best experts on this subject based on the ideXlab platform.
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protein destabilization and loss of protein protein interaction are fundamental mechanisms in cbla type Methylmalonic aciduria
Human Mutation, 2017Co-Authors: Tanja Plessl, Celine Burer, Seraina Lutz, Matthias R Baumgartner, Sean D FroeseAbstract:Mutations in the human MMAA gene cause the metabolic disorder cblA-type Methylmalonic aciduria (MMA), although knowledge of the mechanism of dysfunction remains lacking. MMAA regulates the incorporation of the cofactor adenosylcobalamin (AdoCbl), generated from the MMAB adenosyltransferase, into the destination enzyme methylmalonyl-CoA mutase (MUT). This function of MMAA depends on its GTPase activity, which is stimulated by an interaction with MUT. Here, we present 67 new patients with cblA-type MMA, identifying 19 novel mutations. We biochemically investigated how missense mutations in MMAA in 22 patients lead to disease. About a third confer instability to the recombinant protein in bacterial and human expression systems. All 15 purified mutant proteins demonstrated wild-type like intrinsic GTPase activity and only one (p.Asp292Val), where the mutation is in the GTP binding domain, revealed decreased GTP binding. However, all mutations strongly decreased functional association with MUT by reducing GTPase activity stimulation upon incubation with MUT, while nine mutant proteins additionally lost the ability to physically bind MUT. Finally, all mutations interfered with gating the transfer of AdoCbl from MMAB to MUT. This work suggests loss of functional interaction between MMAA and MUT as a disease-causing mechanism that impacts processing and assembly of a cofactor to its destination enzyme.
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molecular genetic characterization of 151 mut type Methylmalonic aciduria patients and identification of 41 novel mutations in mut
Human Mutation, 2016Co-Authors: Patrick Forny, Seraina Lutz, Matthias R Baumgartner, Sean D Froese, Annesophie Schnellmann, Celine Buerer, Brian FowlerAbstract:Isolated Methylmalonic aciduria (MMA) is an autosomal-recessive disorder of propionate metabolism that is most commonly caused by mutations in the methylmalonyl-CoA mutase (MUT) gene (mut-type MMA). We investigated a cohort of 151 patients, classifying 114 patients as mut0 and 32 as mut− (five not defined). As per the definition, mut− patients showed a higher propionate incorporation ratio in vitro, which was correlated to a considerably later age of onset compared with mut0 patients. In all patients, we found a total of 110 different mutations, of which 41 were novel. While the missense alleles p.Asn219Tyr, p.Arg369His, and p.Arg694Trp recurred in >10 alleles, 47 mutations were identified only once, suggesting many patients carry private mutations. Deficient alleles in the mut− subclass were almost exclusively caused by missense mutations, found disproportionately in the C-terminal cofactor binding domain. On the contrary, only half of the mut0 mutations were of the missense type. Western blot analysis revealed reduced MUT protein for all 34 cell lines (27 mut0, seven mut−) tested, suggesting protein instability as a major mechanism of deficiency in mut-type MMA. This large-scale evaluation helps to characterize the landscape of MUT mutations and their relationship to dysfunction and disease.
Liu Yupeng - One of the best experts on this subject based on the ideXlab platform.
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Five novel SUCLG1 mutations in three Chinese patients with succinate-CoA ligase deficiency noticed by mild Methylmalonic aciduria
BRAIN & DEVELOPMENT, 2016Co-Authors: Liu Yupeng, Ding Yuan, Song Jinqing, Li Xiyuan, Wang Qiao, Yang YanlingAbstract:Objective: Methylmalonic aciduria is the most common organic aciduria in mainland China. Succinate-CoA ligase deficiency causes encephalomyopathy with mitochondrial DNA depletion and mild Methylmalonic aciduria. Patients usually present with severe encephalomyopathy, infantile lactic acidosis, which can be fatal, and mild Methylmalonic aciduria. Patients and methods: Three Chinese patients (two boys and one girl) were hospitalized because of severe encephalomyopathy between 7 and 9 months. They presented with severe psychomotor retardation, hypotonia, dystonia, athetoid movements, seizures, feeding problems and failure to thrive. Mild elevated urine Methylmalonic acid and blood propionylcamitine indicated Methylmalonic aciduria. Gene capture and high-throughput genomic sequencing was carried out. Results: Five novel mutations in SUCLG1 were identified in these patients: c.550G>A (p.G184S) in exon 5, c.751C>T (p.G251S) in exon 7, c.809A>C (p.L270W) in exon 7, c.961C>G (p.A321P) in exon 8 and c.826-2A>G (Splicing) in exon 9 Significant depletion of mtDNA was not observed in the peripheral leukocytes of the three patients in spite of mild decreasing of mitochondrial respiratory chain complex I in two patients and complex V in one patient. After treatment with cobalamin, calcium folinate, L-carnitine, vitamin B1, C, and coenzyme Q10, and nutrition intervention, the patients improved. Conclusions: Succinate-CoA ligase deficiency due to SUCLG1 mutations is a rare cause of Methylmalonic aciduria. Biochemical and gene studies are keys for the differential diagnoses. Three Chinese patients with mild Methylmalonic aciduria were genetically diagnosed using high-throughput genomic sequencing. Five novel pathogenic mutations in SUCLG1 were identified. (c) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.National Nature Science Foundation of China [81471097]; Ministry of Science and Technology [2012BAI09B04]SCI(E)PubMedARTICLEorganic.acid@126.com161-673
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Acute encephalopathy induced by vaccination in an infant with Methylmalonic aciduria cblA
zhonghua er ke za zhi chinese journal of pediatrics, 2015Co-Authors: Liu Yupeng, Wu Tongfei, Wang Haijun, Ding Yuan, Song Jinqing, Li Xiyuan, Zhang Yao, Wang Qiao, Yang YanlingAbstract:We report the first case of acute encephalopathy induced by vaccination in an infant with Methylmalonic aciduria cblA in China.The clinical presentation, blood acylcarnitines analysis, urine organic acids analysis and gene studies of the patient were summarized.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.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.PubMed0162-55
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First Chinese case of successful pregnancy with combined Methylmalonic aciduria and homocystinuria, cblC type
brain development, 2015Co-Authors: Liu Yupeng, Ding Yuan, Song Jinqing, Li Xiyuan, Wang Qiao, Yang YanlingAbstract:Objective: Combined Methylmalonic aciduria (MMA) and homocystinuria, cblC type, is the most common MMA in Mainland China. Its clinical spectrum varies from severe neonatal-onset forms, with brain injury and high mortality to milder forms with late onset. Timely diagnosis and adequate treatment greatly improve the prognosis. In the past 15 years, many Chinese patients with this condition have achieved favorable treatment outcomes, and some of them have reached childbearing age. Here, we report the first case of Chinese woman with cblC undergoing a successful pregnancy and delivering a healthy boy. Methods: A patient of late-onset cblC, who achieved successful pregnancy and delivery of a healthy boy, was enrolled in our studies. The patient and her disease characteristics were analyzed, including age at onset, age at diagnosis, clinical presentation, clinical classification, family history, laboratory findings and MMACHC gene mutation. Results: Our patient presented mild neurological symptoms at the age of 15 years. She had the compound heterozygous mutations, c.315C>G and c.482G>A, on the MMACHC gene. After long-term treatment with cobalamin, calcium folinate, 1-carnitine and betaine, along with normal diet, she recovered completely. At age 23, she visited us for genetic counseling and fetal evaluation at 15 weeks of gestation. Her general condition and the fetal growth were normal. At 20 weeks of gestation, intramuscular cobalamin was changed to pure hydroxocobalamin (1 mg, every other day) because of markedly elevated urine MMA and plasma total homocysteine. In addition, the dosages of 1-carnitine (1 g, p.o., tds), folic acid (5 mg, p.o., tds) and betaine (1 g, p.o., tds) were increased. Protein intake was not restricted. Conclusions: This is the first report of a Chinese woman with cblC, undergoing a successful pregnancy and delivering a healthy baby at term. The favorable outcome of the patient and her fetus should owe much to the mild phenotype of her disease. (C) 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.Clinical NeurologySCI(E)PubMed0ARTICLEorganic.acid@126.com3286-2913