ESPE Abstracts (2014) 82 P-D-3-1-886

3-Ketothiolase Deficiency Induced by ACAT1 Gene Mutation

Li Li, Zhu Min, Mao Huiying & Xiong Feng

The Children’s Hospital of Chongqing Medical University, Chongqing, China

Background: 3-Ketothiolase deficiency (3KTD) is an inherited error of metabolism affecting isoleucine catabolism and ketone body utilization. This disorder is clinically characterized by intermittent ketoacidotic episodes with no clinical symptoms.

Objective and hypotheses: To research the gene mutation of 3 acetoacetyl-CoA thiolase in non-diabetic ketoacidosis and provide a basis for diagnosis of 3KTD.To reveal the role of 3 acetoacetyl-CoA thiolase in isoleucine metabolism, and explore potential mechanisms of 3KTD by gene mutations.

Method: DNA was extracted from blood of a Chinese patient, his family members and healthy children. The entire coding regions of ACAT1 gene with flanking intronic regions were amplified by PCR and directly sequenced, detected the mutation sites. Detected 3 – ketothiolase activity by enzyme assay using fibroblasts.

Results: A127V missense mutation in exon 5 was identified in this patient, no mutation was observed in other tests. Some single nucleotide polymorphisms (SNPs) of ACAT1 gene were detected. A127V mutation activated a cryptic splice-acceptor site and occurred aberrant splicing, leading to 17-amino acids deletion, including the active-site 126Cys. 3-ketothiolase did not retain activity by enzyme assay using fibroblasts.

Conclusion: These results confirmed that c.456C>T caused exon 5 aberrant splicing and may be a potential pathogenesis of 3KTD.

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