Abstract
Objectives
Mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase, T2) is necessary for the catabolism of ketone bodies andisoleucine. T2 deficiency is an autosomal recessive metabolic disorder caused by variant in the ACAT1 gene. In this report, we describe two novel ACAT1 variant identified in a Chinese family.
Case presentation
The 9-month-old male proband was admitted to the pediatric intensive care unit for altered consciousness. At the time of admission, the patient had acidosis, drowsiness, and respiratory failure. Both urine organic acid analyses and LC–MS/MS suggested T2 deficiency. Novel compound heterozygous variant (c.871G>C and c.1016_1017del) in the ACAT1 gene were detected in the proband by WES and verified through direct sequencing. Family analysis demonstrated that the first variant was transmitted from his father and the second variant was from his mother, indicating autosomal recessive inheritance. This report is the first to describe the association of these variant with T2 deficiency based on genetic testing. Although these variant were identified in the patient’s elder sister and elder brother, they continue to be asymptomatic.
Conclusions
We identified two novel ACAT1 variants associated with T2 deficiency. The identification expands the spectrum of known variant linked to the disorder.
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Research funding: None declared.
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Author contributions: (I) Conception and design: Yujuan Wang and Qian Gao. (II) Administrative support: Youpeng Jin. (III) Provision of study materials or patients: Yujuan Wang, Qian Gao, and Youpeng Jin. (IV) Collection and assembly of data: Xiaowei Xin and Yi Yin. (V) Data analysis and interpretation: Yujuan Wang, Qian Gao, and Chun Zhao. (VI) Manuscript writing: All authors. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Shandong Provincial Hospital Affiliated to Shandong First Medical University (Shandong Provincial Hospital) and with the Helsinki Declaration (as revised in 2013).
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