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

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.

journal_name

Mol Genet Metab

authors

Grünert SC,Schmitt RN,Schlatter SM,Gemperle-Britschgi C,Balcı MC,Berg V,Çoker M,Das AM,Demirkol M,Derks TGJ,Gökçay G,Uçar SK,Konstantopoulou V,Christoph Korenke G,Lotz-Havla AS,Schlune A,Staufner C,Tran C,Visser G,S

doi

10.1016/j.ymgme.2017.06.012

subject

Has Abstract

pub_date

2017-09-01 00:00:00

pages

67-75

issue

1-2

eissn

1096-7192

issn

1096-7206

pii

S1096-7192(17)30088-4

journal_volume

122

pub_type

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