The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform
Toshiyuki Fukao - One of the best experts on this subject based on the ideXlab platform.
-
metabolic encephalopathy in beta ketothiolase Deficiency the first report from india
Brain & Development, 2014Co-Authors: Radha Rama Devi Akella, Yuka Aoyama, Chihiro Mori, Lokesh Lingappa, Rohit Cariappa, Toshiyuki FukaoAbstract:Abstract Beta-Ketothiolase Deficiency, or mitochondrial acetoacetyl-CoA thiolase (T2) Deficiency, is a rare autosomal recessive disorder affecting isoleucine catabolism and ketone body metabolism. A patient from South India presented with acute ketoacidosis at 11 months of age. During the acute crisis the C5OH (2-methyl-3-hydroxybutyryl) carnitine and C5:1 (tiglyl) carnitine were elevated and large amounts of 2-methyl-3-hydroxybutyrate, tiglylglycine, and 2-methylacetoacetate were excreted. Brain CT showed bilateral basal ganglia lesions. Potassium ion-activated acetoacetyl-CoA thiolase activity was deficient in the patient’s fibroblasts. The patient is a homozygote for a novel c.578T>G (M193R) mutation. This is the first report of T2 Deficiency confirmed by enzyme and molecular analysis from India.
-
three japanese patients with beta ketothiolase Deficiency who share a mutation c 431a c h144p in acat1 subtle abnormality in urinary organic acid analysis and blood acylcarnitine analysis using tandem mass spectrometry
JIMD reports, 2012Co-Authors: Toshiyuki Fukao, Shinsuke Maruyama, Toshihiro Ohura, Yuki Hasegawa, Mitsuo Toyoshima, Antti M Haapalainen, Naomi Kuwada, Mari Imamura, Isao Yuasa, Rik K WierengaAbstract:Mitochondrial acetoacetyl-CoA thiolase (T2) Deficiency affects both isoleucine catabolism and ketone body metabolism. The disorder is characterized by intermittent ketoacidotic episodes. We report three Japanese patients. One patient (GK69) experienced two ketoacidotic episodes at the age of 9 months and 3 years, and no further episodes until the age of 25 years. She had two uncomplicated pregnancies. GK69 was a compound heterozygote of the c.431A>C (H144P) and c.1168T>C (S390P) mutations in T2 (ACAT1) gene. She was not suspected of having T2 Deficiency during her childhood, but she was diagnosed as T2 deficient at the age of 25 years by enzyme assay using fibroblasts. The other two patients were identical twin siblings who presented their first ketoacidotic crisis simultaneously at the age of 3 years 4 months. One of them (GK77b) died during the first crisis and the other (GK77) survived. Even during severe crises, C5-OH and C5:1 were within normal ranges in their blood acylcarnitine profiles and trace amounts of tiglylglycine and small amounts of 2-methyl-3-hydroxybutyrate were detected in their urinary organic acid profiles. They were H144P homozygotes. This H144P mutation has retained the highest residual T2 activity in the transient expression analysis of mutant cDNA thus far, while the S390P mutation did not retain any residual T2 activity. The “mild” H144P mutation may result in subtle profiles in blood acylcarnitine and urinary organic acid analyses. T2-deficient patients with “mild” mutations have severe ketoacidotic crises but their chemical phenotypes may be subtle even during acute crises.
Gulden Gokcay - One of the best experts on this subject based on the ideXlab platform.
-
clinical presentation and outcome in a series of 32 patients with 2 methylacetoacetyl coenzyme a thiolase mat Deficiency
Molecular Genetics and Metabolism, 2017Co-Authors: Sarah C Grunert, Robert Niklas Schmitt, Sonja Marina Schlatter, Corinne Gemperlebritschgi, Mehmet Cihan Balci, Volker Berg, Mahmut Coker, Mubeccel Demirkol, Terry G J Derks, Gulden GokcayAbstract:2-methylacetoacetyl-coenzyme A thiolase (MAT) Deficiency, also known as Beta-Ketothiolase Deficiency, is an inborn error of ketone body utilization and isoleucine catabolism. It is caused by mutations in the ACAT1 gene and may present with metabolic ketoacidosis. In order to obtain a more comprehensive view on this disease, we have collected clinical and biochemical data as well as information on ACAT1 mutations of 32 patients from 12 metabolic centers in five countries. Patients were between 23 months and 27 years old, more than half of them were offspring of a consanguineous union. 63% of the study participants presented with a metabolic decompensation while most others were identified via newborn screening or family studies. In symptomatic patients, age at manifestation ranged between 5 months and 6.8 years. Only 7% developed a major mental disability while the vast majority was cognitively normal. More than one third of the identified mutations in ACAT1 are intronic mutations which are expected to disturb splicing. We identified several novel mutations but, in agreement with previous reports, no clear genotype-phenotype correlation could be found. Our study underlines that the prognosis in MAT Deficiency is good and MAT deficient individuals may remain asymptomatic, if diagnosed early and preventive measures are applied.
Sass, Jörn Oliver - One of the best experts on this subject based on the ideXlab platform.
-
2-methylacetoacetyl-coenzyme A thiolase (Beta-Ketothiolase) Deficiency: one disease - two pathways
'Springer Science and Business Media LLC', 2020Co-Authors: Grünert, Sarah C., Sass, Jörn OliverAbstract:Background: 2-methylacetoacetyl-coenzyme A thiolase Deficiency (MATD; Deficiency of mitochondrial acetoacetyl-coenzyme A thiolase T2/ “Beta-Ketothiolase”) is an autosomal recessive disorder of ketone body utilization and isoleucine degradation due to mutations in ACAT1. Methods: We performed a systematic literature search for all available clinical descriptions of patients with MATD. Two hundred forty-four patients were identified and included in this analysis. Clinical course and biochemical data are presented and discussed. Results: For 89.6% of patients at least one acute metabolic decompensation was reported. Age at first symptoms ranged from 2 days to 8 years (median 12 months). More than 82% of patients presented in the first 2 years of life, while manifestation in the neonatal period was the exception (3.4%). 77.0% (157 of 204 patients) of patients showed normal psychomotor development without neurologic abnormalities. Conclusion: This comprehensive data analysis provides a systematic overview on all cases with MATD identified in the literature. It demonstrates that MATD is a rather benign disorder with often favourable outcome, when compared with many other organic acidurias
-
2-methylacetoacetyl-coenzyme A thiolase (Beta-Ketothiolase) Deficiency: one disease - two pathways
'Springer Science and Business Media LLC', 2019Co-Authors: Grünert, Sarah Catharina, Sass, Jörn OliverAbstract:Background: 2-methylacetoacetyl-coenzyme A thiolase Deficiency (MATD; Deficiency of mitochondrial acetoacetyl-coenzyme A thiolase T2/ “Beta-Ketothiolase”) is an autosomal recessive disorder of ketone body utilization and isoleucine degradation due to mutations in ACAT1. Methods: We performed a systematic literature search for all available clinical descriptions of patients with MATD. 244 patients were identified and included in this analysis. Clinical course and biochemical data are presented and discussed. Results: For 89.6 % of patients at least one acute metabolic decompensation was reported. Age at first symptoms ranged from 2 days to 8 years (median 12 months). More than 82% of patients presented in the first two years of life, while manifestation in the neonatal period was the exception (3.4%). 77.0% (157 of 204 patients) of patients showed normal psychomotor development without neurologic abnormalities. Conclusion: This comprehensive data analysis provides a systematic overview on all cases with MATD identified in the literature. It demonstrates that MATD is a rather benign disorder with often favourable outcome, when compared with many other organic acidurias
Sarah C Grunert - One of the best experts on this subject based on the ideXlab platform.
-
clinical presentation and outcome in a series of 32 patients with 2 methylacetoacetyl coenzyme a thiolase mat Deficiency
Molecular Genetics and Metabolism, 2017Co-Authors: Sarah C Grunert, Robert Niklas Schmitt, Sonja Marina Schlatter, Corinne Gemperlebritschgi, Mehmet Cihan Balci, Volker Berg, Mahmut Coker, Mubeccel Demirkol, Terry G J Derks, Gulden GokcayAbstract:2-methylacetoacetyl-coenzyme A thiolase (MAT) Deficiency, also known as Beta-Ketothiolase Deficiency, is an inborn error of ketone body utilization and isoleucine catabolism. It is caused by mutations in the ACAT1 gene and may present with metabolic ketoacidosis. In order to obtain a more comprehensive view on this disease, we have collected clinical and biochemical data as well as information on ACAT1 mutations of 32 patients from 12 metabolic centers in five countries. Patients were between 23 months and 27 years old, more than half of them were offspring of a consanguineous union. 63% of the study participants presented with a metabolic decompensation while most others were identified via newborn screening or family studies. In symptomatic patients, age at manifestation ranged between 5 months and 6.8 years. Only 7% developed a major mental disability while the vast majority was cognitively normal. More than one third of the identified mutations in ACAT1 are intronic mutations which are expected to disturb splicing. We identified several novel mutations but, in agreement with previous reports, no clear genotype-phenotype correlation could be found. Our study underlines that the prognosis in MAT Deficiency is good and MAT deficient individuals may remain asymptomatic, if diagnosed early and preventive measures are applied.
Yuka Aoyama - One of the best experts on this subject based on the ideXlab platform.
-
Beta-Ketothiolase Deficiency
SAGE Publishing, 2016Co-Authors: Elsayed Abdelkreem Md Msc, Yuka Aoyama, Hiroki Otsuka, Hideo Sasai, Phd ,tomohiro Hori, Phd ,mohamed Abd El Aal, Phd ,shaimaa Mahmoud, Phd ,toshiyuki FukaoAbstract:Beta-Ketothiolase Deficiency is an inherited disorder of ketone body metabolism and isoleucine catabolism. It typically manifests as recurrent ketoacidotic episodes with characteristic abnormalities in the urinary organic acid profile. However, several challenges in the diagnosis of Beta-Ketothiolase Deficiency have been encountered: atypical presentations have been reported and some other disorders, such as succinyl-CoA:3-oxoacid CoA transferase and 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiencies, can mimic the clinical and/or biochemical signs of Beta-Ketothiolase Deficiency. A final diagnosis of Beta-Ketothiolase Deficiency requires an enzymatic assay and/or a molecular analysis, but some caveats must be considered. Despite the reported missed cases, screening programs have successfully identified an increasing number of patients with Beta-Ketothiolase Deficiency. Early diagnosis and management of Beta-Ketothiolase Deficiency will enable prevention of its serious acute and chronic complications and ultimately improve the prognosis
-
metabolic encephalopathy in beta ketothiolase Deficiency the first report from india
Brain & Development, 2014Co-Authors: Radha Rama Devi Akella, Yuka Aoyama, Chihiro Mori, Lokesh Lingappa, Rohit Cariappa, Toshiyuki FukaoAbstract:Abstract Beta-Ketothiolase Deficiency, or mitochondrial acetoacetyl-CoA thiolase (T2) Deficiency, is a rare autosomal recessive disorder affecting isoleucine catabolism and ketone body metabolism. A patient from South India presented with acute ketoacidosis at 11 months of age. During the acute crisis the C5OH (2-methyl-3-hydroxybutyryl) carnitine and C5:1 (tiglyl) carnitine were elevated and large amounts of 2-methyl-3-hydroxybutyrate, tiglylglycine, and 2-methylacetoacetate were excreted. Brain CT showed bilateral basal ganglia lesions. Potassium ion-activated acetoacetyl-CoA thiolase activity was deficient in the patient’s fibroblasts. The patient is a homozygote for a novel c.578T>G (M193R) mutation. This is the first report of T2 Deficiency confirmed by enzyme and molecular analysis from India.