A novel mutation of Beta-ketothiolase deficiency: The first report from Iran and review of literature

Rahim Vakili, Somayyeh Hashemian

Abstract


347

Background:

Beta-ketothiolase deficiency is a rare autosomal recessive disorder characterized by an inborn error of isoleucine catabolism and affecting ketone body metabolism. Clinical features characterized by intermittent keto acidotic episodes associated with clinical signs and symptoms of toxic encephalopathy such as lethargy, hypotonia, vomiting, tachypnea, and coma in some patients, with an onset during infancy or toddler-hood.

Case presentation:

A two months old girl presented with acute episode of fever and toxic encephalopathy with attack of vomiting, hypotonia, lethargy, tonic clonic seizures and then a day in coma, few days after vaccination .After then similar episodes happened until 7 months age.  . Biochemical tests that suggested diagnose of beta ketothiolase deficiency were attacks of ketoacidosis with urinary exertion of 2-methyl-3-hydroxybutric acid 2-methyl aceto acetic acid tiglylglycine. In genetic assessment we detected a novel homozygous mutation c.664A> C (p. Ser 222 Arg) in ACAT gene. This is a first report of beta ketothiolase deficiency confirmed by molecular analysis from Iran.

Conclusion: we report on a homozygous variant in the ACAT1 gene that is the first time we detect this variant and is a novel mutation. According to the obtained result and patient’s phenotype, we recommended carrier testing for all informative family members to recognize mutations in asymptomatic family members.


Keywords


Beta-ketothiolase deficiency, encephalopathy like symptoms, genetic assay

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References


Hori T, Yamaguchi S, Shinkaku H, Horikawa R, Shigematsu Y, Takayanagi M, et al. Inborn errors of ketone body utilization. Pediatrics International. 2015;57(1):41-8.

2. Abdelkreem E, Otsuka H, Sasai H, Aoyama Y, Hori T, Abd El Aal M, et al. Beta-ketothiolase deficiency: resolving challenges in diagnosis. Journal of Inborn Errors of Metabolism and Screening. 2016;4:2326409816636644.

Fukao T, Mitchell G, Sass JO, Hori T, Orii K, Aoyama Y. Ketone body metabolism and its defects. Journal of inherited metabolic disease. 2014;37(4):541-51.

Weerasinghe W, Jasinge E, Sarathchandra J, Chinthaka R. Intermittent episodes of metabolic ketoacidosis in a seven-year-old boy: Mitochondrial Beta-ketothiolase deficiency. Galle Medical Journal. 2013;18(1).

Law C-Y, Lam C-W, Ching C-k, Yau K-CE, Ho T-w, Lai C-k, et al. NMR-based urinalysis for beta-ketothiolase deficiency. Clinica Chimica Acta. 2015;438:222-5.

Fukao T. Beta-ketothiolase deficiency. Orphanet encylopedia, Semptember 2001. 2004.

Fukao T, Scriver CR, Kondo N, Group TCW. The clinical phenotype and outcome of mitochondrial acetoacetyl-CoA thiolase deficiency (β-ketothiolase or T2 deficiency) in 26 enzymatically proved and mutation-defined patients. Molecular genetics and metabolism. 2001;72(2):109-14.

Daum RS, Mamer O, Lamm P, Scriver C. A" new" disorder of isoleucine catabolism. The Lancet. 1971;298(7737):1289-90.

Mitchell G, Fukao T. Inborn errors of ketone body metabolism. The metabolic and molecular basis of inherited disease. 2001:2327-56.

Hillman RE, Keating JP. Beta-ketothiolase deficiency as a cause of the" ketotic hyperglycinemia syndrome". Pediatrics. 1974;53(2):221-5.

Ozand P, Rashed M, Gascon G, Al Odaib A, Shums A, Nester M, et al. 3-Ketothiolase deficiency: a review and four new patients with neurologic symptoms. Brain and Development. 1994;16:38-45.

Robinson BH, Sherwood WG, Taylor J, Balfe JW, Mamer OA. Acetoacetyl CoA thiolase deficiency: a cause of severe ketoacidosis in infancy simulating salicylism. The Journal of pediatrics. 1979;95(2):214-9.

Buhaş D, Bernard G, Fukao T, Décarie JC, Chouinard S, Mitchell GA. A treatable new cause of chorea: Beta‐ketothiolase deficiency. Movement Disorders. 2013;28(8):1054-6.

Wen P, Chen Z, Wang G, Su Z, Zhang X, Tang G, et al. Analysis of clinical phenotype and ACAT1 gene mutation in a family affected with beta-ketothiolase deficiency. Zhonghua yi xue yi chuan xue za zhi= Zhonghua yixue yichuanxue zazhi= Chinese journal of medical genetics. 2016;33(3):286-91.

Abdelkreem E, Alobaidy H, Aoyama Y, Mahmoud S, El Aal MA, Fukao T. Two Libyan siblings with beta-ketothiolase deficiency: A case report and review of literature. Egyptian Journal of Medical Human Genetics. 2017.

Arani KS, Soltani B. First report of 3-oxothiolase deficiency in iran. International journal of endocrinology and metabolism. 2014 Apr;12(2).

Al-Shamsi A, Hertecant JL, Al-Hamad S, Souid A-K, Al-Jasmi F. Mutation spectrum and birth prevalence of inborn errors of metabolism among Emiratis: a study from Tawam Hospital Metabolic Center, United Arab Emirates. Sultan Qaboos University medical journal. 2014;14(1):e42.

Khneisser I, Adib S, Assaad S, Megarbane A, Karam P. Cost-benefit analysis: Newborn screening for inborn errors of metabolism in Lebanon. Journal of medical screening. 2015;22(4):182-6.

Hassan FA, El-Mougy F, Sharaf SA, Mandour I, Morgan MF, Selim LA, et al. Inborn errors of metabolism detectable by tandem mass spectrometry in Egypt: The first newborn screening pilot study. Journal of medical screening. 2016;23(3):124-9.

Kano M, Fukao T, Yamaguchi S, Orii T, Osumi T, Hashimoto T. Structure and expression of the human mitochondrial acetoacetyl-CoA thiolase-encoding gene. Gene. 1991;109(2):285-90.

Fukao T, Nguyen HT, Nguyen NT, Vu DC, Can NT, Van Pham AT, Nguyen KN, Kobayashi H, Hasegawa Y, Bui TP, Niezen-Koning KE. A common mutation, R208X, identified in Vietnamese patients with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency. Molecular genetics and metabolism. 2010 May 31;100(1):37-41.

Fukao T, Boneh A, Aoki Y, Kondo N. A novel single-base substitution (c. 1124A> G) that activates a 5-base upstream cryptic splice donor site within exon 11 in the human mitochondrial acetoacetyl-CoA thiolase gene. Molecular genetics and metabolism. 2008 Aug 31;94(4):417-21.

Fukao T, Horikawa R, Naiki Y, Tanaka T, Takayanagi M, Yamaguchi S, Kondo N. A novel mutation (c. 951C> T) in an exonic splicing enhancer results in exon 10 skipping in the human mitochondrial acetoacetyl-CoA thiolase gene. Molecular genetics and metabolism. 2010 Aug 31;100(4):339-44.

Abdelkreem E, Alobaidy H, Aoyama Y, Mahmoud S, El Aal MA, Fukao T. Two Libyan siblings with beta-ketothiolase deficiency: A case report and review of literature. Egyptian Journal of Medical Human Genetics. 2017 Jan 4.

Al-Jasmi FA, Al-Shamsi A, Hertecant JL, Al-Hamad SM, Souid AK. Inborn Errors of Metabolism in the United Arab Emirates: Disorders Detected by Newborn Screening (2011–2014). InJIMD Reports, Volume 28 2015 (pp. 127-135). Springer Berlin Heidelberg.

Wen P, Chen Z, Wang G, Su Z, Zhang X, Tang G, Cui D, Liu X, Li C. Analysis of clinical phenotype and ACAT1 gene mutation in a family affected with beta-ketothiolase deficiency. Zhonghua yi xue yi chuan xue za zhi= Zhonghua yixue yichuanxue zazhi= Chinese journal of medical genetics. 2016 Jun;33(3):286-91.

Akella RR, Aoyama Y, Mori C, Lingappa L, Cariappa R, Fukao T. Metabolic encephalopathy in beta-ketothiolase deficiency: The first report from India. Brain and Development. 2014 Jun 30;36(6):537-40.

Fukao T, Maruyama S, Ohura T, Hasegawa Y, Toyoshima M, Haapalainen AM, et al. Three Japanese patients with beta-ketothiolase deficiency who share a mutation, c. 431A> C (H144P) in ACAT1. JIMD Reports-Case and Research Reports, 2011/3: Springer; 2011. p. 107-15.




DOI: https://doi.org/10.22037/ijcn.v12i3.16645

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