Clinical presentation and outcome in a series of 32 patients with 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency

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 comprehens...

Full description

Saved in:
Bibliographic Details
Published in:Molecular genetics and metabolism 2017-09, Vol.122 (1-2), p.67-75
Main Authors: Grünert, Sarah Catharina, Schmitt, Robert Niklas, Schlatter, Sonja Marina, Gemperle-Britschgi, Corinne, Balcı, Mehmet Cihan, Berg, Volker, Çoker, Mahmut, Das, Anibh M., Demirkol, Mübeccel, Derks, Terry G.J., Gökçay, Gülden, Uçar, Sema Kalkan, Konstantopoulou, Vassiliki, Christoph Korenke, G., Lotz-Havla, Amelie Sophia, Schlune, Andrea, Staufner, Christian, Tran, Christel, Visser, Gepke, Schwab, Karl Otfried, Fukao, Toshiyuki, Sass, Jörn Oliver
Format: Article
Language:English
Subjects:
Acetyl-CoA C-Acetyltransferase - genetics
Acetyl-CoA C-Acyltransferase - deficiency
Acetyl-CoA C-Acyltransferase - genetics
Adolescent
Adult
Amino Acid Metabolism, Inborn Errors - complications
Amino Acid Metabolism, Inborn Errors - diagnosis
Amino Acid Metabolism, Inborn Errors - genetics
Amino Acid Metabolism, Inborn Errors - physiopathology
Beta-ketothiolase deficiency
Child
Child, Preschool
Consanguinity
Enzyme activity
Fatty acid metabolism
Fatty Acids - metabolism
Female
Genetic Association Studies
Humans
Infant
Infant, Newborn
Isoleucine - metabolism
Isoleucine degradation
Ketolysis
Ketone Bodies - metabolism
Ketone body utilization
Male
Mutation
Neonatal Screening
Prognosis
Retrospective Studies
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. •Largest multiethnic patient cohort so far with focus on clinical manifestation and outcome•Seven previously unreported mutations in ACAT1, but no obvious correlation between genotype and phenotype.•Broad clinical spectrum. Overall benign phenotypes with many asymptomatic patients, but fatal courses possible.•No obvious negative consequences for patients without long-term protein restriction.
ISSN:1096-7192
1096-7206
DOI:10.1016/j.ymgme.2017.06.012