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Background: Isobutyryl-CoA dehydrogenase deficiency (IBDD) is a rare autosomal recessive metabolic disorder resulting from variants in ACAD8, and is poorly understood, as only dozens of cases have been reported previously. Based on a newborn screening program, we evaluated the incidence, phenotype and genotype of IBDD as well as the prognosis. Moreover, we reviewed the variant spectrum in ACAD8 associated with IBDD. Methods: Forty unrelated patients with IBDD were retrospectively screened for newborns between Jan 2012 and Dec 2020. Tandem mass spectrometry (MS/MS) was used to determine the concentrations of C4-acylcarnitine, C4/C2 (acetylcarnitine), and C4/C3 (propionylcarnitine). All suspected cases were genetically tested by metabolic genes panel. Results: The incidence of IBDD here was 1: 62,599. All patients presented continuously elevated C4-acylcarnitine levels with higher ratios of C4/C2 and C4/C3. Isobutyrylglycine occurred in only 8 patients. During follow-up, four patients had a transient motor delay, and two patients had growth delay. Notably, one case harbored both ACAD8 compound heterozygous variants and a KMT2A de novo variant (c.2739del, p.E914Rfs*35), with IBDD and Wiedemann–Steiner syndrome together, had exact severe global developmental delay. All patients were regularly monitored once they were diagnosed, and each patient gradually had a normal diet after 6 months of age. After 3–108 months of follow-up, most individuals were healthy except the case harboring the KMT2A variant. A total of 16 novel variants in ACAD8, c.4_5delCT, c.109C > T, c.110–2A > T, c.236G > A, c.259G > A, c.381–14G > A, c.413delA, c.473A > G, c.500delG, c.758 T > G, c.842–1G > A, c.911A > T, c.989G > A, c.1150G > C, c.1157A > G and c.1165C > T, were identified. Along with a literature review on 51 ACAD8 variants in 81 IBDD patients, we found that the most common variant was c.286G > A (27.2%), which has been observed solely in the Chinese population to date, followed by c.1000C > T (8.6%), c.1176G > T (3.7%) and c.455 T > C (3.1%). Conclusion: The concentration of C4-acylcarnitine in NBS plus subsequent genetic testing is necessary for IBDD diagnosis. Both the genotypes and ACAD8 variants in IBDD are highly heterogeneous, and no significant correlations between genotype and phenotype are present here in patients with IBDD. Our IBDD cohort with detaied clinical characteristics, genotypes and long-term prognosis will be helpful for the diagnosis and management of patients with IBDD in the future. [ABSTRACT FROM AUTHOR]

What is known and Objectives The serotoninergic receptor 5-hydroxytryptamine (serotonin) receptor 3 ( HTR3) is instrumental in the regulation of nausea and emesis (vomiting).This study investigated whether common genomic variations of the A and B subunits of HTR3 ( HTR3A, HTR3B) are associated with the incidence of post-operative vomiting in a Chinese Han population. Methods Two hundred and thirty-one female Chinese Han patients undergoing gynaecological surgery with standardized general anaesthesia were recruited for the study. Clinical symptoms after surgery were recorded and direct DNA sequencing was performed to detect polymorphisms of HTR3A and HTR3B. Results Five single nucleotide polymorphisms ( SNPs) in HTR3A and HTR3B were found, with R2 > 0·8 and minor allele frequency > 10%. One of these (rs3758987 in HTR3B) was statistically associated with vomiting, after adjusting for body weight, body mass index and duration of general anaesthesia in dominant and additive models ( P = 0·047 and P = 0·034). What is new and Conclusion The HTR3B rs3758987 SNP might serve as a predictor of post-operative vomiting in Chinese Han patients undergoing gynaecological laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Reference 1 Feng J. Phenotype, genotype and long-term prognosis of 40 Chinese patients with isobutyryl-CoA dehydrogenase deficiency and a review of variant spectra in ACAD8. The correct sentence should read: "Another special IBDD patient, with a severe lack of speech development and lack of social interactions, was reported to be associated with autism [18].". [Extracted from the article]