Two Infants With Beta-Ketothiolase Deficiency Identified by Newborn Screening in China

Yang, Yuqi; Jiang, Shu hong; Liu, Shuang; Han, Xiao; Wang, Ying; Wang, Lei lei; Yu, Bin

doi:10.3389/fgene.2019.00451

Cited by 4 publications

(7 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this cohort, 29 Chinese patients were genetically diagnosed with BKTD, 14 of which were diagnosed through NBS while 17 were previously reported [ 12 – 16 ]. During the study period, a total of 16,088,190 newborns were screened.…”

Section: Resultsmentioning

confidence: 99%

“…The specific objectives of the study were: (a) to investigate the baseline levels of amino acids and acylcarnitines in BKTD; (b) to evaluate the importance of C4OH, along with C5OH and C5:1 in BKTD screening; and (c) to further understand the incidence, clinical features, genetic features, and prognosis of BKTD. We systematically reviewed the available BKTD clinical reports that included the Chinese population [ 12 – 16 ] and retrospectively analyzed the biochemical, clinical, and molecular features of 29 Chinese BKTD patients from our NBS and selective metabolic screening (SMS) data. Previously, C4OH was primarily used to evaluate the metabolic profile of BKTD; however, elevated levels of C4OH can often be observed in our patients during NBS.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

C4OH is a potential newborn screening marker—a multicenter retrospective study of patients with beta-ketothiolase deficiency in China

Lin

Yang

Yang³

et al. 2021

Orphanet J Rare Dis

View full text Add to dashboard Cite

Background Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutation of ACAT1 that affects both isoleucine catabolism and ketolysis. There is little information available regarding the incidence, newborn screening (NBS), and mutational spectrum of BKTD in China. Results We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published data from Chinese BKTD patients. A total of 16,088,190 newborns were screened and 14 patients were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. In total, twenty-nine patients were genetically diagnosed with BKTD, 12 of which were newly identified. Most patients exhibited typical blood acylcarnitine and urinary organic acid profiles. Interestingly, almost all patients (15/16, 94%) showed elevated 3-hydroxybutyrylcarnitine (C4OH) levels. Eighteen patients presented with acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of nine patients were triggered by infections, diarrhea, or an inflammatory response to vaccination. Approximately two-thirds of patients had favorable outcomes, one showed a developmental delay and three died. Twenty-seven distinct variants were identified in ACAT1, among which five were found to be novel. Conclusion This study presented the largest series of BKTD cohorts in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by the addition of C4OH to the current panel of 3-hydroxyisovalerylcarnitine and tiglylcarnitine markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in the Chinese population were expanded with five newly identified variants.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

C4OH is a potential newborn screening marker—a multicenter retrospective study of patients with beta-ketothiolase deficiency in China

Lin

Yang

Yang³

et al. 2021

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…[ 74 ] For detailed characterization of various IEMs at the biochemical and genetic levels, MS/MS and NGS were effectively used in China. [ 8,75 ]…”

Section: Efforts To Initiate Nbs Program In Asian and Other Countriesmentioning

confidence: 99%

“…By now, it is recognized that early detection of the disease can improve the outcomes for many of the treatable IEMs, which has resulted in the setup of advanced newborn metabolic screening programs. [8][9][10][11][12] Advanced "omics" approaches which are required for the development of NBS programs are discussed below.…”

Section: Diagnostic Tools For Iemsmentioning

confidence: 99%

Need and Challenges in Establishing Newborn Screening Programs for Inherited Metabolic Disorders in Developing Countries

et al. 2023

View full text Add to dashboard Cite

Even in this post genomic era, no national level newborn screening (NBS) programs for inborn errors of metabolism (IEMs) are yet available in several developing countries including Pakistan. Through NBS, various IEMs can be screened using minute quantities of biofluids. Targeted metabolomics and genomic techniques are the main approaches used for NBS. However, lack of technical expertise and such high-end "omics" based analytical facilities, and meager funding for healthcare in developing countries are the major reasons for unavailability of NBS programs. As it is reflected by only a handful reports about IEMs from Pakistan with population of ≈220 million and consanguinity rate of about 70%, which suggests an unmet need for an NBS program owing to reasonably high prevalence of inherited diseases. Around 200 IEMs are potentially treatable if diagnosed at an earlier stage through biochemical marker and genetic screening, so such patients can get benefit from the NBS program. This overview will help to persuade the stakeholders to setup NBS programs in developing countries including Pakistan, due to multitude of benefits for IEMs; timely diagnosis and early treatment can help the patients to live a nearly healthy life, reduced suffering of the family and minimal burden on society or national healthcare system.

show abstract

“…The overall incidence of BKTD was 1 in 1,149,156 births (Table 1). In total, 29 Chinese patients were genetically diagnosed as BKTD in this cohort, 17 had been previously reported [12][13][14][15][16]. The median C4OH concentration was 1.38 ± 0.94 µmol/L (range 0.26-3.58 µmol/L, reference value 0.02-0.3 µmol/L), almost all patients (15/16, 94%) showed elevated C4OH levels except for one patient (Supplemental Table S1, No.…”

Section: Bktd Nbs and Acylcarnitine Analysismentioning

confidence: 99%

C4OH is a Potential Screening Marker - A Multicenter Retrospective Study of Patients with Beta-Ketothiolase Deficiency in China

Lin

Yang

Yang³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutations in ACAT1 that affects both isoleucine catabolism and ketolysis. Scant information is available regarding the incidence, newborn screening (NBS), and mutational spectrum in China.Methods: We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published Chinese BKTD patients data.Results: Totally 16,088,190 newborns were screened and 14 were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. Twenty-nine patients were genetically diagnosed as BKTD and 12 patients were newly identified. Most patients showed typical blood acylcarnitine and urinary organic acid profiles. In particular, almost all patients (15/16, 94%) showed elevated C4OH levels. Eighteen patients presented acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of 9 patients were triggered by infections, diarrhea, and vaccination. About two thirds of patients have favorable outcomes, one showed developmental delay, while three had died. Twenty-seven distinct variants were identified in ACAT1, among which 5 were found to be novel.Conclusion: This study presented the largest series of BKTD cohort in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by adding C4OH to the current panel of C5OH and C5:1 markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in Chinese population were expanded with 5 newly identified variants.

show abstract

Two Infants With Beta-Ketothiolase Deficiency Identified by Newborn Screening in China

Cited by 4 publications

References 24 publications

C4OH is a potential newborn screening marker—a multicenter retrospective study of patients with beta-ketothiolase deficiency in China

C4OH is a potential newborn screening marker—a multicenter retrospective study of patients with beta-ketothiolase deficiency in China

Need and Challenges in Establishing Newborn Screening Programs for Inherited Metabolic Disorders in Developing Countries

C4OH is a Potential Screening Marker - A Multicenter Retrospective Study of Patients with Beta-Ketothiolase Deficiency in China

Contact Info

Product

Resources

About