title: Characterization and outcome of 41 patients with beta-ketothiolase deficiency: 10 years' experience of a medical center in northern Vietnam.
abstract: Beta-ketothiolase (T2) deficiency is an inherited disease of isoleucine and ketone body metabolism caused by mutations in the ACAT1 gene. Between 2005 and 2016, a total of 41 patients with T2 deficiency were identified at a medical center in northern Vietnam, with an estimated incidence of one in 190,000 newborns. Most patients manifested ketoacidotic episodes of varying severity between 6 and 18 months of age. Remarkably, 28% of patients showed high blood glucose levels (up to 23.3 mmol/L). Ketoacidotic episodes recurred in 43% of patients. The age of onset, frequency of episodes, and identified genotype did not affect patient outcomes that were generally favorable, with the exception of seven cases (five died and two had neurological sequelae). Custom-tailored acute and follow-up management was critical for a positive clinical outcome. Two null mutations, c.622C>T (p.Arg208*) and c.1006-1G>C (p.Val336fs), accounted for 66% and 19% of all identified ACAT1 mutant alleles, respectively. Most patients showed characteristic biochemical abnormalities. A newborn screening program could be expected to have a high yield in Vietnam. Investigation findings of haplotypes linked to the most common ACAT1 mutation (c.622C>T) are consistent with an ancient common founder of mutation-bearing chromosomes belonging to the Kinh ethnic population. The direct management and long-term follow-up of a large number of T2-deficient patients enabled us to study the natural history of this rare disease.
authors.affiliation: National Children's Hospital, La Thanh Road, Dong Da District, Hanoi, Vietnam.
authors.forename: Khanh Ngoc
authors.initials: KN
authors.lastname: Nguyen
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Yanagido 1-1, Gifu, 501-1194, Japan.|Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt.
authors.forename: Elsayed
authors.identifier: 0000-0002-8976-2989
authors.initials: E
authors.lastname: Abdelkreem
authors.affiliation: Institute of Clinical Biochemistry, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.|Center for the Study of Rare Hereditary Diseases, Niguarda Ca' Granda Metropolitan Hospital, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Colombo
authors.affiliation: Department of Pediatrics, Shimane University School of Medicine, Izumo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: National Children's Hospital, La Thanh Road, Dong Da District, Hanoi, Vietnam.
authors.forename: Ngoc Thi Bich
authors.initials: NT
authors.lastname: Can
authors.affiliation: National Children's Hospital, La Thanh Road, Dong Da District, Hanoi, Vietnam.
authors.forename: Thao Phuong
authors.initials: TP
authors.lastname: Bui
authors.affiliation: National Children's Hospital, La Thanh Road, Dong Da District, Hanoi, Vietnam.
authors.forename: Hai Thanh
authors.initials: HT
authors.lastname: Le
authors.affiliation: National Children's Hospital, La Thanh Road, Dong Da District, Hanoi, Vietnam.
authors.forename: Mai Thi Chi
authors.initials: MT
authors.lastname: Tran
authors.affiliation: Vinmec International Hospital, Hanoi, Vietnam.
authors.forename: Hoan Thi
authors.initials: HT
authors.lastname: Nguyen
authors.affiliation: Ministry of Science and Technology, Hanoi, Vietnam.
authors.forename: Hung Thanh
authors.initials: HT
authors.lastname: Trinh
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Yanagido 1-1, Gifu, 501-1194, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Aoyama
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Yanagido 1-1, Gifu, 501-1194, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Sasai
authors.affiliation: Department of Pediatrics, Shimane University School of Medicine, Izumo, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Yanagido 1-1, Gifu, 501-1194, Japan. toshi-gif@umin.net.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.affiliation: National Children's Hospital, La Thanh Road, Dong Da District, Hanoi, Vietnam. dungvu@nhp.org.vn.
authors.forename: Dung Chi
authors.initials: DC
authors.lastname: Vu
mesh_terms: D000102:Acetyl-CoA C-Acyltransferase / Q000172:deficiency* / Q000235:genetics; D000483:Alleles; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics; D015997:Neonatal Screening / Q000379:methods; D014744:Vietnam
chemical_list: D000102:Acetyl-CoA C-Acyltransferase