Background:Propionic acidemia(PA)is caused by a deficiency of propionyl CoA carboxylase.A characteristic urine organic acid profile includes 3-hydroxypropionate,methylcitrate,tiglylglycine,and propionylglycine.The dia...Background:Propionic acidemia(PA)is caused by a deficiency of propionyl CoA carboxylase.A characteristic urine organic acid profile includes 3-hydroxypropionate,methylcitrate,tiglylglycine,and propionylglycine.The diagnosis of PA is confirmed by detection of mutations in the PCCA or PCCB genes.We herein report the clinical and molecular findings of four Thai patients with PA.Methods:Clinical findings of four Thai patients with PA were retrospectively reviewed.Urine organic acids were analyzed by gas chromatography-mass spectrometry.PCR-sequencing analyses of encoding exons and intron/exon boundaries of the PCCA and PCCB genes were performed.Results:All patients had neonatal onset of PA.One patient died of cardiomyopathy,and another one of pneumonia and metabolic decompensation.The remainder experienced significant neurocognitive impairment.Mutation analysis of the PCCA gene identified homozygous c.1284+1G>A in patient 1,c.230G>A(p.R77Q)and c.1855C>T(p.R619X)in patient 2,homozygous c.2125T>C(p.S709P)in patient 3,and only one mutant allele,c.231+1G>T in patient 4.No PCCB mutation was identified.Four mutations including c.230G>A,c.231+1G>T,c.1855C>T,and c.2125T>C have not been reported previously.Conclusions:The clinical and molecular study of these Thai patients provided additional knowledge of the genotype and phenotype characteristics of PA.The results of the study suggested that PCCA mutations in Asian populations were distinct from those of other populations.展开更多
文摘Background:Propionic acidemia(PA)is caused by a deficiency of propionyl CoA carboxylase.A characteristic urine organic acid profile includes 3-hydroxypropionate,methylcitrate,tiglylglycine,and propionylglycine.The diagnosis of PA is confirmed by detection of mutations in the PCCA or PCCB genes.We herein report the clinical and molecular findings of four Thai patients with PA.Methods:Clinical findings of four Thai patients with PA were retrospectively reviewed.Urine organic acids were analyzed by gas chromatography-mass spectrometry.PCR-sequencing analyses of encoding exons and intron/exon boundaries of the PCCA and PCCB genes were performed.Results:All patients had neonatal onset of PA.One patient died of cardiomyopathy,and another one of pneumonia and metabolic decompensation.The remainder experienced significant neurocognitive impairment.Mutation analysis of the PCCA gene identified homozygous c.1284+1G>A in patient 1,c.230G>A(p.R77Q)and c.1855C>T(p.R619X)in patient 2,homozygous c.2125T>C(p.S709P)in patient 3,and only one mutant allele,c.231+1G>T in patient 4.No PCCB mutation was identified.Four mutations including c.230G>A,c.231+1G>T,c.1855C>T,and c.2125T>C have not been reported previously.Conclusions:The clinical and molecular study of these Thai patients provided additional knowledge of the genotype and phenotype characteristics of PA.The results of the study suggested that PCCA mutations in Asian populations were distinct from those of other populations.
