The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Magdalena Ugarte - One of the best experts on this subject based on the ideXlab platform.
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45-Year-old female with Propionic Acidemia, renal failure, and premature ovarian failure; late complications of Propionic Acidemia?
Molecular genetics and metabolism, 2011Co-Authors: Christina Lam, Lourdes R. Desviat, Celia Pérez-cerdá, Magdalena Ugarte, Bruce Barshop, Stephen D. CederbaumAbstract:We describe a 45-year-old patient who was diagnosed with Propionic Acidemia in infancy, who experienced an unstable first two years of life but who eventually had a good developmental outcome. She developed severe renal failure requiring renal transplantation in her forties and premature ovarian failure. Renal failure and premature ovarian failure have not previously been associated with Propionic Acidemia. We hypothesize that Propionic Acidemia may have contributed to these complications, and discuss several possible mechanisms for this, emphasizing mainly the electron transport chain/mitochondrial energy deficiency hypothesis.
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Prenatal diagnosis of Propionic Acidemia.
Prenatal diagnosis, 2004Co-Authors: Celia Pérez-cerdá, Lourdes R. Desviat, Belén Pérez, Begoña Merinero, P. Rodríguez Pombo, Magdalena UgarteAbstract:In this report we summarize our experience in prenatal diagnosis of Propionic Acidemia (PA) since 1987. Overall, we have investigated 25 pregnancies at risk from 19 unrelated families. Until genetic structure of the genes involved in PA was elucidated, prenatal diagnosis has been successfully performed by means of metabolite quantitation and/or enzymatic assays in foetal issue. Today, direct propionyl-CoA carboxylase activity assay in combination with molecular analysis in chorion villi can be regarded as a fast and reliable method of choice for prenatal diagnosis of this organic Acidemia.
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Propionic Acidemia: identification of twenty-four novel mutations in Europe and North America.
Molecular genetics and metabolism, 2003Co-Authors: Belén Pérez, Lourdes R. Desviat, Celia Pérez-cerdá, Pilar Rodríguez-pombo, S. Clavero, Rosa Navarrete, Magdalena UgarteAbstract:Propionic Acidemia is an inherited metabolic disease caused by the deficiency of the mitochondrial protein propionyl-CoA carboxylase (PCC), one of the four biotin-dependent enzymes. PCC is a multimeric protein composed of two different alpha- and beta-PCC subunits, nuclearly encoded by the PCCA and PCCB genes, respectively. Mutations in either gene cause the clinically heterogeneous disease Propionic Acidemia. In this work we describe the mutational analysis of PCCA and PCCB deficient patients from different European countries (Spain, Italy, Belgium, Croatia, and Austria) and from America (mainly USA). We report 24 novel PA mutations, nine affecting the PCCA gene and 15 affecting the PCCB gene. They include six missense mutations, one nonsense mutation, one point exonic mutation affecting splicing, seven splicing mutations affecting splice sequences, and nine short insertions or deletions, only two in-frame. We have found a highly heterogenous spectrum of PCCA mutations, most of the PCCA deficient patients are homozygous carrying a unique genotype. The PCCA mutational spectrum includes a high proportion of short insertions or deletions affecting one nucleotide. In the PCCA mutant alleles analyzed we have also found one single nucleotide change, a novel nonsynonymous SNP. On the other hand, the PCCB deficient patients carry a more reduced spectrum of mutations, 50% of them are missense. This work represents an extensive update of the mutational study of Propionic Acidemia providing important information about the worldwide distribution of PA mutations and representing another essential part in the study of the phenotype-genotype correlations for the prediction of the metabolic outcome and for the implementation of treatments tailored to each PA patient.
Celia Pérez-cerdá - One of the best experts on this subject based on the ideXlab platform.
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45-Year-old female with Propionic Acidemia, renal failure, and premature ovarian failure; late complications of Propionic Acidemia?
Molecular genetics and metabolism, 2011Co-Authors: Christina Lam, Lourdes R. Desviat, Celia Pérez-cerdá, Magdalena Ugarte, Bruce Barshop, Stephen D. CederbaumAbstract:We describe a 45-year-old patient who was diagnosed with Propionic Acidemia in infancy, who experienced an unstable first two years of life but who eventually had a good developmental outcome. She developed severe renal failure requiring renal transplantation in her forties and premature ovarian failure. Renal failure and premature ovarian failure have not previously been associated with Propionic Acidemia. We hypothesize that Propionic Acidemia may have contributed to these complications, and discuss several possible mechanisms for this, emphasizing mainly the electron transport chain/mitochondrial energy deficiency hypothesis.
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Prenatal diagnosis of Propionic Acidemia.
Prenatal diagnosis, 2004Co-Authors: Celia Pérez-cerdá, Lourdes R. Desviat, Belén Pérez, Begoña Merinero, P. Rodríguez Pombo, Magdalena UgarteAbstract:In this report we summarize our experience in prenatal diagnosis of Propionic Acidemia (PA) since 1987. Overall, we have investigated 25 pregnancies at risk from 19 unrelated families. Until genetic structure of the genes involved in PA was elucidated, prenatal diagnosis has been successfully performed by means of metabolite quantitation and/or enzymatic assays in foetal issue. Today, direct propionyl-CoA carboxylase activity assay in combination with molecular analysis in chorion villi can be regarded as a fast and reliable method of choice for prenatal diagnosis of this organic Acidemia.
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Propionic Acidemia: identification of twenty-four novel mutations in Europe and North America.
Molecular genetics and metabolism, 2003Co-Authors: Belén Pérez, Lourdes R. Desviat, Celia Pérez-cerdá, Pilar Rodríguez-pombo, S. Clavero, Rosa Navarrete, Magdalena UgarteAbstract:Propionic Acidemia is an inherited metabolic disease caused by the deficiency of the mitochondrial protein propionyl-CoA carboxylase (PCC), one of the four biotin-dependent enzymes. PCC is a multimeric protein composed of two different alpha- and beta-PCC subunits, nuclearly encoded by the PCCA and PCCB genes, respectively. Mutations in either gene cause the clinically heterogeneous disease Propionic Acidemia. In this work we describe the mutational analysis of PCCA and PCCB deficient patients from different European countries (Spain, Italy, Belgium, Croatia, and Austria) and from America (mainly USA). We report 24 novel PA mutations, nine affecting the PCCA gene and 15 affecting the PCCB gene. They include six missense mutations, one nonsense mutation, one point exonic mutation affecting splicing, seven splicing mutations affecting splice sequences, and nine short insertions or deletions, only two in-frame. We have found a highly heterogenous spectrum of PCCA mutations, most of the PCCA deficient patients are homozygous carrying a unique genotype. The PCCA mutational spectrum includes a high proportion of short insertions or deletions affecting one nucleotide. In the PCCA mutant alleles analyzed we have also found one single nucleotide change, a novel nonsynonymous SNP. On the other hand, the PCCB deficient patients carry a more reduced spectrum of mutations, 50% of them are missense. This work represents an extensive update of the mutational study of Propionic Acidemia providing important information about the worldwide distribution of PA mutations and representing another essential part in the study of the phenotype-genotype correlations for the prediction of the metabolic outcome and for the implementation of treatments tailored to each PA patient.
William L. Nyhan - One of the best experts on this subject based on the ideXlab platform.
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Pitfalls in the prenatal diagnosis of Propionic Acidemia.
Clinical genetics, 2008Co-Authors: P. D. Buchanan, S. G. Kahler, Lawrence Sweetman, William L. NyhanAbstract:Prenatal diagnosis of Propionic Acidemia can be performed by two independent methods: measuring an elevated quantity of the metabolite methylcitrate in amniotic fluid; and demonstrating deficient activity of propionyl-CoA carboxylase in amniocytes cultured from the fluid. Discordant results in a pregnancy at risk for Propionic Acidemia were obtained. Elevated concentration of methylcitrate indicated an affected fetus, but the activity of propionyl-CoA carboxylase was normal. An affected female infant was born. Chromosome variant analysis demonstrated that between passage two and four overgrowth of the female fetal cells by contaminating maternal cells led to the "false negative" results obtained by enzyme assay. This experience demonstrates the value of analysis of abnormal metabolites in amniotic fluid and highlights a problem that could confound the prenatal diagnosis of any condition assessed by enzyme activity.
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Neurologic nonmetabolic presentation of Propionic Acidemia.
Archives of neurology, 1999Co-Authors: William L. Nyhan, Carolyn Bay, Elizabeth Webb Beyer, Melissa MaziAbstract:Background Patients with Propionic Acidemia usually present in the neonatal period with life-threatening ketoacidosis, often complicated by hyperammonemia. It was thought that the neurologic abnormalities seen in this disease were exclusively the consequences of these acute crises. Experience with 2 patients with Propionic Acidemia indicates that this disease may present first with prominent neurologic disease without the life-threatening episodes of ketoacidosis that usually serve as the alerting signals for a diagnosis of an organic Acidemia. Objective To examine the clinical and metabolic aspects of 2 patients with a phenotype that suggested disease of the basal ganglia. Design Examination of patterns of organic acids of the urine and enzyme assay for propionyl-CoA carboxylase in fibroblasts and lymphocytes. Setting Referral population to a biochemical genetics laboratory. Patients Two patients whose prominent features were hypotonia followed by spastic quadriparesis and choreoathetosis. Both had seizures. One patient was mildly mentally retarded but grew normally physically. The other had profound mental retardation and failure to thrive; he also self-mutilated his lower lip. Self-injurious behavior has not been reported in this disease. Main Outcome Measures Clinical description, blood ammonia levels, organic acid levels in the urine, and enzyme activity. Results Excretion of metabolites, including methylcitrate, was typical. Residual activity of propionyl-CoA carboxylase approximated 5% of the control in each patient. Conclusions Propionic Acidemia can present as a pure neurologic disease without acute episodes of massive ketoacidosis. Hyperammonemia may occur after infancy in some patients, presenting as Reye syndrome.
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Acute basal ganglia infarction in Propionic Acidemia.
Journal of child neurology, 1995Co-Authors: Richard H. Haas, Deborah Marsden, Sylvia B. Capistrano-estrada, Ronald L. Hamilton, Marjorie R. Grafe, Wade Wong, William L. NyhanAbstract:An 8-year-old girl with Propionic Acidemia had acute and rapidly fatal symmetric necrosis of the caudate, globus pallidus, and putamen. Clinical presentation was with acute aphasia, generalized hypotonia, and muscle weakness. There was no evidence of metabolic decompensation, and analysis of the organic acids of the urine indicated good metabolic control. Organic acids in the cerebrospinal fluid were unremarkable. These observations indicate that the pathophysiology of "metabolic stroke" is more complicated than previously thought.
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Neuropathology of Propionic Acidemia: a report of two patients with basal ganglia lesions.
Journal of child neurology, 1995Co-Authors: Ronald L. Hamilton, William L. Nyhan, Richard H. Haas, Henry C. Powell, Marjorie R. GrafeAbstract:Propionic Acidemia is a rare genetic disorder of amino acid metabolism caused by deficient activity of propionyl coenzyme A carboxylase. Neuropathologic changes previously reported in infants have been white-matter vacuolization or spongiosis. In children who survive beyond infancy, abnormalities have been found primarily in the basal ganglia. We report neuropathologic findings in two patients with Propionic Acidemia diagnosed in infancy who survived 35 months and 9 years, respectively. Examination of the brain of the 35-month-old boy showed vascular and parenchymal mineralization, focal pallor and spongy change, and foci of acute neuronal injury. These changes were similar to those previously described. The 9-year-old girl was in good metabolic control when she died, and presented a neuropathologic picture not previously described. She was found at autopsy to have acute hemorrhagic lesions in the caudate, putamen, and globus pallidus bilaterally and in the left ventral thalamus. There was focal neuronal ...
Lourdes R. Desviat - One of the best experts on this subject based on the ideXlab platform.
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45-Year-old female with Propionic Acidemia, renal failure, and premature ovarian failure; late complications of Propionic Acidemia?
Molecular genetics and metabolism, 2011Co-Authors: Christina Lam, Lourdes R. Desviat, Celia Pérez-cerdá, Magdalena Ugarte, Bruce Barshop, Stephen D. CederbaumAbstract:We describe a 45-year-old patient who was diagnosed with Propionic Acidemia in infancy, who experienced an unstable first two years of life but who eventually had a good developmental outcome. She developed severe renal failure requiring renal transplantation in her forties and premature ovarian failure. Renal failure and premature ovarian failure have not previously been associated with Propionic Acidemia. We hypothesize that Propionic Acidemia may have contributed to these complications, and discuss several possible mechanisms for this, emphasizing mainly the electron transport chain/mitochondrial energy deficiency hypothesis.
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Prenatal diagnosis of Propionic Acidemia.
Prenatal diagnosis, 2004Co-Authors: Celia Pérez-cerdá, Lourdes R. Desviat, Belén Pérez, Begoña Merinero, P. Rodríguez Pombo, Magdalena UgarteAbstract:In this report we summarize our experience in prenatal diagnosis of Propionic Acidemia (PA) since 1987. Overall, we have investigated 25 pregnancies at risk from 19 unrelated families. Until genetic structure of the genes involved in PA was elucidated, prenatal diagnosis has been successfully performed by means of metabolite quantitation and/or enzymatic assays in foetal issue. Today, direct propionyl-CoA carboxylase activity assay in combination with molecular analysis in chorion villi can be regarded as a fast and reliable method of choice for prenatal diagnosis of this organic Acidemia.
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Propionic Acidemia: identification of twenty-four novel mutations in Europe and North America.
Molecular genetics and metabolism, 2003Co-Authors: Belén Pérez, Lourdes R. Desviat, Celia Pérez-cerdá, Pilar Rodríguez-pombo, S. Clavero, Rosa Navarrete, Magdalena UgarteAbstract:Propionic Acidemia is an inherited metabolic disease caused by the deficiency of the mitochondrial protein propionyl-CoA carboxylase (PCC), one of the four biotin-dependent enzymes. PCC is a multimeric protein composed of two different alpha- and beta-PCC subunits, nuclearly encoded by the PCCA and PCCB genes, respectively. Mutations in either gene cause the clinically heterogeneous disease Propionic Acidemia. In this work we describe the mutational analysis of PCCA and PCCB deficient patients from different European countries (Spain, Italy, Belgium, Croatia, and Austria) and from America (mainly USA). We report 24 novel PA mutations, nine affecting the PCCA gene and 15 affecting the PCCB gene. They include six missense mutations, one nonsense mutation, one point exonic mutation affecting splicing, seven splicing mutations affecting splice sequences, and nine short insertions or deletions, only two in-frame. We have found a highly heterogenous spectrum of PCCA mutations, most of the PCCA deficient patients are homozygous carrying a unique genotype. The PCCA mutational spectrum includes a high proportion of short insertions or deletions affecting one nucleotide. In the PCCA mutant alleles analyzed we have also found one single nucleotide change, a novel nonsynonymous SNP. On the other hand, the PCCB deficient patients carry a more reduced spectrum of mutations, 50% of them are missense. This work represents an extensive update of the mutational study of Propionic Acidemia providing important information about the worldwide distribution of PA mutations and representing another essential part in the study of the phenotype-genotype correlations for the prediction of the metabolic outcome and for the implementation of treatments tailored to each PA patient.
Belén Pérez - One of the best experts on this subject based on the ideXlab platform.
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Prenatal diagnosis of Propionic Acidemia.
Prenatal diagnosis, 2004Co-Authors: Celia Pérez-cerdá, Lourdes R. Desviat, Belén Pérez, Begoña Merinero, P. Rodríguez Pombo, Magdalena UgarteAbstract:In this report we summarize our experience in prenatal diagnosis of Propionic Acidemia (PA) since 1987. Overall, we have investigated 25 pregnancies at risk from 19 unrelated families. Until genetic structure of the genes involved in PA was elucidated, prenatal diagnosis has been successfully performed by means of metabolite quantitation and/or enzymatic assays in foetal issue. Today, direct propionyl-CoA carboxylase activity assay in combination with molecular analysis in chorion villi can be regarded as a fast and reliable method of choice for prenatal diagnosis of this organic Acidemia.
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Propionic Acidemia: identification of twenty-four novel mutations in Europe and North America.
Molecular genetics and metabolism, 2003Co-Authors: Belén Pérez, Lourdes R. Desviat, Celia Pérez-cerdá, Pilar Rodríguez-pombo, S. Clavero, Rosa Navarrete, Magdalena UgarteAbstract:Propionic Acidemia is an inherited metabolic disease caused by the deficiency of the mitochondrial protein propionyl-CoA carboxylase (PCC), one of the four biotin-dependent enzymes. PCC is a multimeric protein composed of two different alpha- and beta-PCC subunits, nuclearly encoded by the PCCA and PCCB genes, respectively. Mutations in either gene cause the clinically heterogeneous disease Propionic Acidemia. In this work we describe the mutational analysis of PCCA and PCCB deficient patients from different European countries (Spain, Italy, Belgium, Croatia, and Austria) and from America (mainly USA). We report 24 novel PA mutations, nine affecting the PCCA gene and 15 affecting the PCCB gene. They include six missense mutations, one nonsense mutation, one point exonic mutation affecting splicing, seven splicing mutations affecting splice sequences, and nine short insertions or deletions, only two in-frame. We have found a highly heterogenous spectrum of PCCA mutations, most of the PCCA deficient patients are homozygous carrying a unique genotype. The PCCA mutational spectrum includes a high proportion of short insertions or deletions affecting one nucleotide. In the PCCA mutant alleles analyzed we have also found one single nucleotide change, a novel nonsynonymous SNP. On the other hand, the PCCB deficient patients carry a more reduced spectrum of mutations, 50% of them are missense. This work represents an extensive update of the mutational study of Propionic Acidemia providing important information about the worldwide distribution of PA mutations and representing another essential part in the study of the phenotype-genotype correlations for the prediction of the metabolic outcome and for the implementation of treatments tailored to each PA patient.
