INTRODUCTIONα-ketoadipate(α-KA),an intermediate in thecatabolism of L-lysine,hydroxylysine,and L-tryptophan,undergoes oxidative deearboxylation toform glutaryl-CoA and then dehydrogenates to formcrotonyl-CoA,the lat...INTRODUCTIONα-ketoadipate(α-KA),an intermediate in thecatabolism of L-lysine,hydroxylysine,and L-tryptophan,undergoes oxidative deearboxylation toform glutaryl-CoA and then dehydrogenates to formcrotonyl-CoA,the latter undergoes furtherdegradation and enters in TCA cycle,as shown inFigure 1.α-ketoadipic aciduria (Mckusick 245130)is a rare inborn error in the metabolism of α-KA展开更多
Methylmalonic aciduria（MMA） is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase（MCM,mut complementation group） or in the synthesis of the MCM cofactor a...Methylmalonic aciduria（MMA） is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase（MCM,mut complementation group） or in the synthesis of the MCM cofactor adenosylcobalamin（cbl complementation groups）.The defects in the mut complementation group accounts for the largest number of patients with isolated MMA.At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now.This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients.Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry（GC-MS）,and from some of their parents as well.Amplification and direct sequencing of the MUT coding regions（exon 2-13） and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations.In this group,six novel mutations in the MUT gene,c.424AG（p.T142A）,c.786TG（p.S262R）,c.808GC（p.G270R）,c.1323_1324insA,c.1445-1GA and c.1676＋77AC were identified.p.T142A and p.G270R were respectively detected at a heterozygous level in one patient.Two previously reported mutations,c.682CT（p.R228X） and c.323GA（p.R108H） were also found in this study.In addition,six previously described single nucleotide polymorphism（SNP）,c.636AG（p.K212K）,c.1495GA（p.A499T）,c.1595AG（p.H532R）,c.1992GA（p.A664A）,c.2011GA（p.V671I） and c.1677-53AG were identified.In this study,we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.展开更多
Objective To follow up study on α-ketoadipic aciduria , which is a rare inborn error of metabolism of L-ly sine, hydroxy-L-lysine, and L-tryptophan. Methods The case with α-ketoadipic aciduria was investigated ...Objective To follow up study on α-ketoadipic aciduria , which is a rare inborn error of metabolism of L-ly sine, hydroxy-L-lysine, and L-tryptophan. Methods The case with α-ketoadipic aciduria was investigated clinically and metabolites were detected by using gas chromatography-mass spectrometry techniques during a period of 15 years (9months～ 15years). Results The case had growth retardation at the onset but later grew normally. The urinary metabolites showed persisent abnormality compatible with α-ketoadipic aciduria. The concentrations of α-ketoadipate , α-aminoadipate and α-hy droxyadipate were 33mmol/mol creatinine, 92～266mmol/mol creatinine and 17～28mmol/mol creatinine , respectively. Glutarate also increased in their urine. Conclusion The study suggested the clinical course of a-ketoadipic aciduria is benign and the clinical manifestations are various. The follow-up study on this case with α-ketoadipic aciduria must be continued.展开更多
基金the grant from the J.A.M.W.Ogyaa Donation Foundation (JODF)National Science Foundation for High-Technology Research Center of Kanazawa Medical University (H98-3).
文摘INTRODUCTIONα-ketoadipate(α-KA),an intermediate in thecatabolism of L-lysine,hydroxylysine,and L-tryptophan,undergoes oxidative deearboxylation toform glutaryl-CoA and then dehydrogenates to formcrotonyl-CoA,the latter undergoes furtherdegradation and enters in TCA cycle,as shown inFigure 1.α-ketoadipic aciduria (Mckusick 245130)is a rare inborn error in the metabolism of α-KA
基金supported by grants from the National Basic Research Program of China(2005CB522507)the 11th Five-year Plan of National Science & Technology(2006BAI05A07)
文摘Methylmalonic aciduria（MMA） is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase（MCM,mut complementation group） or in the synthesis of the MCM cofactor adenosylcobalamin（cbl complementation groups）.The defects in the mut complementation group accounts for the largest number of patients with isolated MMA.At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now.This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients.Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry（GC-MS）,and from some of their parents as well.Amplification and direct sequencing of the MUT coding regions（exon 2-13） and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations.In this group,six novel mutations in the MUT gene,c.424AG（p.T142A）,c.786TG（p.S262R）,c.808GC（p.G270R）,c.1323_1324insA,c.1445-1GA and c.1676＋77AC were identified.p.T142A and p.G270R were respectively detected at a heterozygous level in one patient.Two previously reported mutations,c.682CT（p.R228X） and c.323GA（p.R108H） were also found in this study.In addition,six previously described single nucleotide polymorphism（SNP）,c.636AG（p.K212K）,c.1495GA（p.A499T）,c.1595AG（p.H532R）,c.1992GA（p.A664A）,c.2011GA（p.V671I） and c.1677-53AG were identified.In this study,we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.
文摘Objective To follow up study on α-ketoadipic aciduria , which is a rare inborn error of metabolism of L-ly sine, hydroxy-L-lysine, and L-tryptophan. Methods The case with α-ketoadipic aciduria was investigated clinically and metabolites were detected by using gas chromatography-mass spectrometry techniques during a period of 15 years (9months～ 15years). Results The case had growth retardation at the onset but later grew normally. The urinary metabolites showed persisent abnormality compatible with α-ketoadipic aciduria. The concentrations of α-ketoadipate , α-aminoadipate and α-hy droxyadipate were 33mmol/mol creatinine, 92～266mmol/mol creatinine and 17～28mmol/mol creatinine , respectively. Glutarate also increased in their urine. Conclusion The study suggested the clinical course of a-ketoadipic aciduria is benign and the clinical manifestations are various. The follow-up study on this case with α-ketoadipic aciduria must be continued.
