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


Abstract

2-methylacetoacetyl-coenzymeA 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 viewon 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
whilemost otherswere 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 identifiedmutations in ACAT1 are intronicmutations 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 andMAT deficient individuals may remain asymptomatic, if diagnosed early and preventive measures are applied.

Abstract

2-methylacetoacetyl-coenzymeA 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 viewon 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
whilemost otherswere 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 identifiedmutations in ACAT1 are intronicmutations 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 andMAT deficient individuals may remain asymptomatic, if diagnosed early and preventive measures are applied.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:15 September 2017
Deposited On:16 Jan 2018 09:45
Last Modified:19 Feb 2018 10:25
Publisher:Elsevier
ISSN:1096-7192
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.ymgme.2017.06.012
PubMed ID:28689740

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