Biochemical, molecular, and clinical features of patients with glutaric acidemia type 1 identified through large-scale newborn screening in Zhejiang Province, China

Lin, Yiming; Zhu, Xun; Zhang, Chao; Yin, Xiaoshan; Miao, Haixia; Hu, Zhenzhen; Yang, Junpeng; Wu, Benqing; Huang, Xinwen

doi:10.1016/j.cca.2022.03.026

Cited by 3 publications

(8 citation statements)

References 23 publications

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“…In this study, 18 patients with GA1 were identified via 1.15 million NBS results, and the incidence was approximately 1 in 63,948 births in Fujian Province. This incidence is much higher than that in Zhejiang Province (1:221,053) [ 18 ] and Jining City (1:171,411) in eastern China [ 20 ].…”

Section: Discussionmentioning

confidence: 91%

“…Early detection and timely intervention for inborn metabolic disorders through NBS are crucial for preventing adverse clinical symptoms in affected individuals. With the widespread application of MS/MS, GC/MS, and NGS, patients with GA1 have been diagnosed timely [ 18 , 23 , 24 ]. The estimated prevalence of GA1 varies widely depending on race and region, ranging from 1:125,000 to 1:250 newborns [ 25 – 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…GA1 is a treatable disorder [ 1 ], and newborn screening (NBS) programs for GA1 have been implemented in many developed countries [ 12 – 14 ]. The incidence of GA1 and characteristics of the variants of GCDH gene have been reported in certain different populations, including the Chinese population [ 14 – 18 ]. However, the prevalence of GA1 ranges from 1/221,053 to 1/52,078 among the populations in different regions of China [ 18 – 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…The incidence of GA1 and characteristics of the variants of GCDH gene have been reported in certain different populations, including the Chinese population [ 14 – 18 ]. However, the prevalence of GA1 ranges from 1/221,053 to 1/52,078 among the populations in different regions of China [ 18 – 22 ]. Limited data are available on the prevalence and mutational spectrum of GCDH in GA1 in China based on large-scale NBS.…”

Section: Introductionmentioning

confidence: 99%

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Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China

Lin

Zhao

et al. 2023

Orphanet J Rare Dis

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Background Glutaric acidemia type 1 (GA1) is a rare autosomal recessive inherited metabolic disorder caused by variants in the gene encoding the enzyme glutaryl-CoA dehydrogenase (GCDH). The estimated prevalence of GA1 and the mutational spectrum of the GCDH gene vary widely according to race and region. The aim of this study was to assess the acylcarnitine profiles and genetic characteristics of patients with GA1 in Fujian Province, southeastern China. Results From January 2014 to December 2022, a total of 1,151,069 newborns (631,016 males and 520,053 females) were screened using MS/MS in six newborn screening (NBS) centers in Fujian Province and recruited for this study. Through NBS, 18 newborns (13 females and 5 males) were diagnosed with GA1. Thus, the estimated incidence of GA1 was 1 in 63,948 newborns in Fujian province. In addition, 17 patients with GA1 were recruited after clinical diagnosis. All but one patient with GA1 had a remarkable increase in glutarylcarnitine (C5DC) concentrations. The results of urinary organic acid analyses in 33 patients showed that the concentration of glutaric acid (GA) increased in all patients. The levels of C5DC and GA in patients identified via NBS were higher than those in patients identified via clinical diagnosis (P < 0.05). A total of 71 variants of 70 alleles were detected in patients with GA1, with 19 different pathogenic variants identified. The three most prevalent variants represented 73.23% of the total and were c.1244-2 A > C, p.(?) (63.38%), c.1261G > A, p.Ala421Thr (5.63%), and c.406G > T, p.Gly136Cys (4.22%). The most abundant genotype observed was c.[1244-2 A > C]; [1244-2 A > C] (18/35, 52.43%) and its phenotype corresponded to high excretors (HE, GA > 100 mmol/mol Cr). Conclusions In conclusion, we investigated the biochemical and molecular features of 35 unrelated patients with GA1. C5DC concentrations in dried blood spots and urinary GA are effective indicators for a GA1 diagnosis. Our study also identified a GCDH variant spectrum in patients with GA1 from Fujian Province, southeastern China. Correlation analysis between genotypes and phenotypes provides preliminary and valuable information for genetic counseling and management.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China

Lin

Zhao

et al. 2023

Orphanet J Rare Dis

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“…As shown in Table 4 , the GCDH c.1261G > A [p.(Ala421Thr)] variant was detected in 4 Chinese GAI patients, namely GAI-054, GAI-091, GAI-093, and GAI-094, all combined with c.1244-2 A > C (homozygous in GAI-054). GAI-054, GAI-093, and GAI-094 were identified by NBS [ 12 , 13 ], while GAI-091 were identified by a clinical exome sequencing cohort for developmental disorders [ 14 ]. Pedigree analysis was clear only in GAI-091 (c.1244-2 A > C from father and c.1261G > A from mother).…”

Section: Resultsmentioning

confidence: 99%

Chinese genetic variation database of inborn errors of metabolism: a systematic review of published variants in 13 genes

Guo¹,

Jiang²,

Xu³

2023

Orphanet J Rare Dis

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Background Population-specific variation database of inborn errors of metabolism (IEMs) is essential for precise genetic diagnosis and disease prevention. Here we presented a systematic review of clinically relevant variants of 13 IEMs genes reported among Chinese patients. Methods A systematic search of the following electronic databases for 13 IEMs genes was conducted: PubMed-NCBI, China national knowledge infrastructure and Wanfang databases. Patient data was extracted from articles eligible for inclusion and recorded in Excel electronic form using a case-by-case approach. Results A total of 218 articles, 93 published in English and 125 in Chinese, were retrieved. After variant annotation and deduplication, 575 unique patients (241 from articles published in Chinese) were included in the population-specific variation database. Patients identified by newborn screening and symptomatic presentation were 231 (40.17%) and 344 (59.83%), respectively. Biallelic variants were observed in 525/575 (91.3%). Among the 581 unique variants identified, 83 (14.28%) were described ≥ 3 times and 97 (16.69%) were not recorded in Clinvar or HGMD. Four variants were reclassified as benign and dozens of confusing variants deserved further research. Conclusion This review provides a unique resource of the well-characterized diseases and causative variants that have accumulated in Chinese population and is a preliminary attempt to build the Chinese genetic variation database of IEMs.

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Clinical features and GCDH gene variants in three Chinese families with glutaric aciduria type 1: A case series and literature review

Chen,

Zhang,

Cao

et al. 2024

Molecular Genetics and Metabolism Reports

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Biochemical, molecular, and clinical features of patients with glutaric acidemia type 1 identified through large-scale newborn screening in Zhejiang Province, China

Cited by 3 publications

References 23 publications

Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China

Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China

Chinese genetic variation database of inborn errors of metabolism: a systematic review of published variants in 13 genes

Clinical features and GCDH gene variants in three Chinese families with glutaric aciduria type 1: A case series and literature review

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