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Clinical presentation and outcome in a series of 32 patients with 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency.
Mol Genet Metab 2017; 122(1-2):67-75MG

Abstract

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 23months and 27years 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 5months and 6.8years. 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.

Authors+Show Affiliations

Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.Clinical Chemistry & Biochemistry and Children's Research Center, University Children's Hospital, Zürich, Switzerland.Division of Pediatric Nutrition and Metabolism, Department of Pediatrics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.Elbe Kliniken, Stade, Germany.Metabolism Unit, Department of Pediatrics, Ege University Medical Faculty, Izmir, Turkey.University Children's Hospital, Hannover Medical School, Hannover, Germany.Division of Pediatric Nutrition and Metabolism, Department of Pediatrics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.Section of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Division of Pediatric Nutrition and Metabolism, Department of Pediatrics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.Metabolism Unit, Department of Pediatrics, Ege University Medical Faculty, Izmir, Turkey.Department of Pediatrics, Medical University of Vienna, Vienna, Austria.Department of Pediatric Neurology, Klinikum Oldenburg, Oldenburg, Germany.Dr. von Hauner Children's Hospital, University of Munich, Munich, Germany.Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University, Düsseldorf, Germany.Department of General Pediatrics, Division of Neuropediatrics and Pediatric Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany.Center for Molecular Diseases, Divison of Genetic Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands.Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.Department of Pediatrics, Graduate School of Medicine, Gifu University, and Division of Clinical Genetics, Gifu University Hospital, Gifu, Japan.Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany; Clinical Chemistry & Biochemistry and Children's Research Center, University Children's Hospital, Zürich, Switzerland; Bioanalytics & Biochemistry, Department of Natural Sciences, University of Applied Sciences, Rheinbach, Germany. Electronic address: joern.oliver.sass@h-brs.de.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28689740

Citation

Grünert, Sarah Catharina, et al. "Clinical Presentation and Outcome in a Series of 32 Patients With 2-methylacetoacetyl-coenzyme a Thiolase (MAT) Deficiency." Molecular Genetics and Metabolism, vol. 122, no. 1-2, 2017, pp. 67-75.
Grünert SC, Schmitt RN, Schlatter SM, et al. Clinical presentation and outcome in a series of 32 patients with 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency. Mol Genet Metab. 2017;122(1-2):67-75.
Grünert, S. C., Schmitt, R. N., Schlatter, S. M., Gemperle-Britschgi, C., Balcı, M. C., Berg, V., ... Sass, J. O. (2017). Clinical presentation and outcome in a series of 32 patients with 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency. Molecular Genetics and Metabolism, 122(1-2), pp. 67-75. doi:10.1016/j.ymgme.2017.06.012.
Grünert SC, et al. Clinical Presentation and Outcome in a Series of 32 Patients With 2-methylacetoacetyl-coenzyme a Thiolase (MAT) Deficiency. Mol Genet Metab. 2017;122(1-2):67-75. PubMed PMID: 28689740.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical presentation and outcome in a series of 32 patients with 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency. AU - Grünert,Sarah Catharina, AU - Schmitt,Robert Niklas, AU - Schlatter,Sonja Marina, AU - Gemperle-Britschgi,Corinne, AU - Balcı,Mehmet Cihan, AU - Berg,Volker, AU - Çoker,Mahmut, AU - Das,Anibh M, AU - Demirkol,Mübeccel, AU - Derks,Terry G J, AU - Gökçay,Gülden, AU - Uçar,Sema Kalkan, AU - Konstantopoulou,Vassiliki, AU - Christoph Korenke,G, AU - Lotz-Havla,Amelie Sophia, AU - Schlune,Andrea, AU - Staufner,Christian, AU - Tran,Christel, AU - Visser,Gepke, AU - Schwab,Karl Otfried, AU - Fukao,Toshiyuki, AU - Sass,Jörn Oliver, Y1 - 2017/06/27/ PY - 2017/02/05/received PY - 2017/06/25/revised PY - 2017/06/25/accepted PY - 2017/7/12/pubmed PY - 2018/5/19/medline PY - 2017/7/11/entrez KW - Beta-ketothiolase deficiency KW - Enzyme activity KW - Fatty acid metabolism KW - Isoleucine degradation KW - Ketolysis KW - Ketone body utilization SP - 67 EP - 75 JF - Molecular genetics and metabolism JO - Mol. Genet. Metab. VL - 122 IS - 1-2 N2 - 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 23months and 27years 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 5months and 6.8years. 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. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/28689740/Clinical_presentation_and_outcome_in_a_series_of_32_patients_with_2-methylacetoacetyl-coenzyme_A_thiolase_(MAT)_deficiency L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(17)30088-4 DB - PRIME DP - Unbound Medicine ER -