17. Biochemical characteristics of beta-ketothiolase deficiency patients
Main Article Content
Abstract
Beta-ketothiolase deficiency is a metabolic disorder caused by mutations in the ACAT1 gene (the T2 gene) located on chromosome 11 (11q22.3-q23). The disease is characterized with episodes of acute ketoacidosis and no clinical symptombetween episodes. Mutations in the T2 gene causes disruption of the degradation of isoleucine and ketone in the body. Biochemical tests play an important role in the screening and diagnosis of beta-ketothiolase deficiency. This retrospective and descriptive case series study was carried out to describe the blood acylcarnitine and organic acid urinary characteristics of patients with beta-ketothiolase deficiency. Blood acylcarnitine were measured by Tandem Mass Spectrometry (MS/MS) and analysis of urine organic acids was performed by Gas Chromatography/Mass Spectroscopy (GC/MS). A total of 30 patients with beta-ketothiolase deficiency at the National Children's Hospital from April 2017 to January 2023 were included in this study. The study results showed among 23 patiens participating in the screening, 19/23 reported an increase in the concentration of acylcarnitin C5:1, 20/23 increased C5:OH, 18/23 patients increased both C5:1 and C5:OH indexes; 1 patient had only increased C5:1; 2 patients only had increased C5:OH; 2 patients did not increase both indexes. Results of urinary organic acid analysis of 26 patients showed increased concentrations of urinary acid 2MAA (6/26), 2M3HB (23/26), TIG (13/26) in patients with beta-ketothiolase deficiency. Blood acylcarnitine measurement by MS/MS could not ensure the sensitivity of 100% in screening beta-ketothiolase deficiency, even in symptomatic patients. The characteristic pattern of urine organic acid with elevated excretion of three metabolites (2MAA, 2M3HB and TIG) were not seen in all study cohort.
Article Details
Keywords
Beta-ketothiolase deficiency, Tandem Mass Spectrometry (MS/MS), Gas Chromatography/Mass Spectroscopy (GC/MS)
References
2. Daum RS, Lamm PH, Mamer OA, et al. A “new” disorder of isoleucine catabolism. Lancet. Dec 11 1971;2(7737):1289-90. doi:10.1016/s0140-6736(71)90605-2
3. Fukao T. Beta-ketothiolase deficiency. Orphanet encyclopedia, September 2001.
4. Fukao T, Zhang GX, Sakura N, et al. The mitochondrial acetoacetyl-CoA thiolase (T2) deficiency in Japanese patients: urinary organic acid and blood acylcarnitine profiles under stable conditions have subtle abnormalities in T2-deficient patients with some residual T2 activity. J Inherit Metab Dis. 2003;26(5):423-31. doi:10.1023/a:1025117226051
5. Mak CM, Lee HC, Chan AY, et al. Inborn errors of metabolism and expanded newborn screening: review and update. Crit Rev Clin Lab Sci. Nov 2013;50(6):142-62. doi:10.3109/10408363.2013.847896
6. Nguyen KN, Abdelkreem E, Colombo R, et al. Characterization and outcome of 41 patients with beta-ketothiolase deficiency: 10 years’ experience of a medical center in northern Vietnam. J Inherit Metab Dis. May 2017;40(3):395-401. doi:10.1007/s10545-017-0026-6
7. Nguyễn Ngọc Khánh. Nghiên cứu kiểu hình, kiểu gen và kết quả điều trị của bệnh nhân thiếu enzym Beta-ketothiolase ở Việt Nam. Luận án tiến sỹ y học. Trường Đại học Y Hà Nội. 2017.
8. Fukao T, Sasai H, Aoyama Y, et al. Recent advances in understanding beta-ketothiolase (mitochondrial acetoacetyl-CoA thiolase, T2) deficiency. J Hum Genet. Feb 2019;64(2):99-111. doi:10.1038/s10038-018-0524-x
9. Grünert SC, Schmitt RN, Schlatter SM, et al. Clinical presentation and outcome in a series of 32 patients with 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency. Mol Genet Metab. Sep 2017;122(1-2):67-75. doi:10.1016/j.ymgme.2017.06.012
10. Thadchanamoorthy V, Dayasiri K. Unexplained Tachypneoa and Severe Metabolic Acidosis in a Three-Month-Old Child: A Rare Presentation of Beta-Ketothiolose Deficiency. Cureus. Feb 2022;14(2):e21934. doi:10.7759/cureus.21934