Newborn screening for isovaleric acidemia in Quanzhou, China

Lin, Yiming; Chen, Dongmei; Peng, Weilin; Wang, Kunyi; Lin, Weihua; Zhuang, Jianlong; Zheng, Zhiyong; Li, Min; Fu, Qingliu

doi:10.1016/j.cca.2020.06.010

Cited by 8 publications

(5 citation statements)

References 26 publications

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“…Dried blood spot (DBS) samples were delivered by cold-chain transportation to our NBS center within three days. DBS samples were pre-processed and then quantified using a mass spectrometer, and internal and external quality controls were performed as previously described [ 33 ]. Newborns with elevated C5DC levels were called back.…”

Section: Methodsmentioning

confidence: 99%

Biochemical and molecular features of Chinese patients with glutaric acidemia type 1 detected through newborn screening

Lin¹,

Wang²,

Cai³

et al. 2021

Orphanet J Rare Dis

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Background Glutaric acidemia type 1 (GA1) is a treatable disorder affecting cerebral organic acid metabolism caused by a defective glutaryl-CoA dehydrogenase (GCDH) gene. GA1 diagnosis reports following newborn screening (NBS) are scarce in the Chinese population. This study aimed to assess the acylcarnitine profiles and genetic characteristics of patients with GA1 identified through NBS. Results From January 2014 to September 2020, 517,484 newborns were screened by tandem mass spectrometry, 102 newborns with elevated glutarylcarnitine (C5DC) levels were called back. Thirteen patients were diagnosed with GA1, including 11 neonatal GA1 and two maternal GA1 patients. The incidence of GA1 in the Quanzhou region was estimated at 1 in 47,044 newborns. The initial NBS results showed that all but one of the patients had moderate to markedly increased C5DC levels. Notably, one neonatal patient with low free carnitine (C0) level suggest primary carnitine deficiency (PCD) but was ultimately diagnosed as GA1. Nine neonatal GA1 patients underwent urinary organic acid analyses: eight had elevated GA and 3HGA levels, and one was reported to be within the normal range. Ten distinct GCDH variants were identified. Eight were previously reported, and two were newly identified. In silico prediction tools and protein modeling analyses suggested that the newly identified variants were potentially pathogenic. The most common variant was c.1244-2 A>C, which had an allelic frequency of 54.55% (12/22), followed by c.1261G>A (p.Ala421Thr) at 9.09% (2/22). Conclusions Neonatal GA1 patients with increased C5DC levels can be identified through NBS. Maternal GA1 patients can also be detected using NBS due to the low C0 levels in their infants. Few neonatal GA1 patients may have atypical acylcarnitine profiles that are easy to miss during NBS; therefore, multigene panel testing should be performed in newborns with low C0 levels. This study indicates that the GCDH variant spectra were heterogeneous in this southern Chinese cohort.

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Section: Methodsmentioning

confidence: 99%

Biochemical and molecular features of Chinese patients with glutaric acidemia type 1 detected through newborn screening

Lin¹,

Wang²,

Cai³

et al. 2021

Orphanet J Rare Dis

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“…The main function of CrAT in peroxisomes is to aid in the export of products of peroxisomal b-oxidation (Westin et al, 2008). In the murine cardiomyocyte cytosol, the (Forni et al, 2010); glutaric aciduria type 2 (Forni et al, 2010); ethylmalonic encephalopathy (Forni et al, 2010); gestational diabetes (Roy et al, 2018) Decreased Traumatic brain injury (Jeter et al, 2013) Urine Increased Glutaric aciduria type 2 (Sugiyama et al, 1990); multiple acyl-CoA dehydrogenase deficiency (Kidouchi et al, 1988); acute coronary syndrome (Wang et al, 2018) Isovalerylcarnitine (C5:0 I) Blood Increased Isovaleric acidemia (Shigematsu et al, 2007;Forni et al, 2010;Couce et al, 2017;Lin et al, 2020); glutaric aciduria type 2 (Forni et al, 2010); 3hydroxy-3-methylglutaryl-CoA lyase deficiency (Ma et al, 2011;V aclav ık et al, 2020); cardiovascular diseases (Kukharenko et al, 2020); acute kidney injury (Wan et al, 2019) Decreased Daytime sleepiness (Pak et al, 2018); inflammatory bowel disease (Danese et al, 2011); ulcerative colitis (Bene et al, 2006); traumatic brain injury (Jeter et al, 2013) Urine Increased Glutaric aciduria type 2 (Shimizu et al, 1991); multiple acyl-CoA dehydrogenation deficiency (Kidouchi et al, 1988) 2-Methylbutyrylcarnitine (C5:0 M) Blood Increased Short/branched-chain acyl-CoA dehydrogenase deficiency/2-methylbutyryl-CoA dehydrogenase deficiency (Madsen et al, 2006;Forni et al, 2010); glutaric aciduria type 2 (Forni et al, 2010); gout (Huang et al, 2020); nonalcoholic steatohepatitis (Kalhan et al, 2011) Decreased Pediatric obesity (Farook et al, 2015); traumatic brain injury (Jeter et…”

Section: A Enzymology Of Acylcarnitine Biosynthesismentioning

confidence: 99%

Acylcarnitines: Nomenclature, Biomarkers, Therapeutic Potential, Drug Targets, and Clinical Trials

et al. 2022

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“…According to previous reports, c.1199A>G (p.Tyr371Cys) and c.1208A>G (p.Tyr403Cys) are common among the Han Chinese population ( 17 ). The variant c.466-3_466-2CA>GG (originally reported as c.457-3_2CA>GC) is common in both Thai and Korean populations ( 4 , 22 ); c.932C>T (p.Ala282Val) has been reported as a recurrent variant in White populations ( 26 ); c.367G>A (p.Gly123Arg) has been described as a common variant in Whites settled in South Africa ( 15 ); c.158G>C (p.Arg53Pro) was the most common variant in the Mexican population ( 27 ); and p.Arg395Gln may be a common variant in the UAE population ( 23 ). Based on the literature review, the hotspots in the mainland China and Taiwan are 53, 120, 214, 339, 371, 395, 398, and 403 ( Figure 9 ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the genotype–phenotype correlation in isovaleric acidaemia: A case report of long-term follow-up of a chinese patient and literature review

Liu

Liu²,

Fan³

et al. 2022

Front. Neurol.

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BackgroundIsovaleric acidaemia (IVA), characterized by an acute metabolic crisis and psychomotor delay, is a rare inherited metabolic disease caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD).MethodsWe report the case of a Chinese patient with IVA who was admitted to Tianjin Children's Hospital and followed up for 8 years. Genetic analysis of the patient and his parents was conducted using the whole-exome sequencing and Sanger sequencing. We searched for similar reported cases in the PubMed and Wanfang databases using the term “isovaleric acidaemia,” reviewed the related literature to obtain a summary of the clinical and genetic characteristics, and analyzed the genotype–phenotype correlations.ResultsThe patient presented with encephalopathic symptoms, such as vomiting, lethargy, and somnolence. We identified compound heterozygous variants of the IVD gene, including the unreported variant c.224A>G (p.Asn75Ser) and the reported variant c.1195G>C (p.Asp399His). The child was prescribed a low-protein diet supplemented with L-carnitine. During the 8-year follow-up, no metabolic disorder or encephalopathic symptoms recurred. At present, the child is 11 years of age and has normal mental and motor performance. Another 154 cases identified in 25 relevant references were combined with this case, resulting in a sample of 155 patients, including 52 asymptomatic patients, 64 with neonatal onset, and 39 with the chronic intermittent disease with onset from ages of 1 month to 10 years (median age, 2 years). Among articles that reported sex, the male-to-female ratio was 1:1.06. The cardinal symptoms included vomiting, lethargy, “sweaty foot” odor, poor feeding, developmental delay, and epilepsy. The proportion of variants in regions 123–159 and 356–403 of the IVD protein was greater in symptomatic patients than in asymptomatic patients. Conversely, in asymptomatic patients, the proportion of variants in the 282–318 region was greater than in symptomatic patients.ConclusionThis case report describes an unreported variant c.224A>G (p.Asn75Ser) of the IVD gene, and summarizes previously reported cases. Furthermore, the correlation between the genotype and clinical phenotype of IVA is analyzed to improve the understanding of this disease.

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Newborn screening for isovaleric acidemia in Quanzhou, China

Cited by 8 publications

References 26 publications

Biochemical and molecular features of Chinese patients with glutaric acidemia type 1 detected through newborn screening

Biochemical and molecular features of Chinese patients with glutaric acidemia type 1 detected through newborn screening

Acylcarnitines: Nomenclature, Biomarkers, Therapeutic Potential, Drug Targets, and Clinical Trials

Analysis of the genotype–phenotype correlation in isovaleric acidaemia: A case report of long-term follow-up of a chinese patient and literature review

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