Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China
Abstract 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 ra...
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-023-02833-z |
| _version_ | 1797769321701703680 |
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| author | Jinfu Zhou Guilin Li Lin Deng Peiran Zhao Yinglin Zeng Xiaolong Qiu Jinying Luo Liangpu Xu |
| author_facet | Jinfu Zhou Guilin Li Lin Deng Peiran Zhao Yinglin Zeng Xiaolong Qiu Jinying Luo Liangpu Xu |
| author_sort | Jinfu Zhou |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T21:07:11Z |
| format | Article |
| id | doaj.art-abaf0f2bfea244338e16c2c5e1c9ba0a |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-03-12T21:07:11Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
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| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-abaf0f2bfea244338e16c2c5e1c9ba0a2023-07-30T11:24:41ZengBMCOrphanet Journal of Rare Diseases1750-11722023-07-011811710.1186/s13023-023-02833-zBiochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern ChinaJinfu Zhou0Guilin Li1Lin Deng2Peiran Zhao3Yinglin Zeng4Xiaolong Qiu5Jinying Luo6Liangpu Xu7Medical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityDepartment of Preventive Medicine, School of Public Health, Fujian Medical UniversityObstetrics and Gynecology Department, Fujian Maternity and Child Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityMedical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityMedical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityMedical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityObstetrics and Gynecology Department, Fujian Maternity and Child Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityMedical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical UniversityAbstract 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.https://doi.org/10.1186/s13023-023-02833-zAcylcarnitine profileGCDHGlutaric acidemia type 1Southeastern ChinaVariant |
| spellingShingle | Jinfu Zhou Guilin Li Lin Deng Peiran Zhao Yinglin Zeng Xiaolong Qiu Jinying Luo Liangpu Xu Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China Orphanet Journal of Rare Diseases Acylcarnitine profile GCDH Glutaric acidemia type 1 Southeastern China Variant |
| title | Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China |
| title_full | Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China |
| title_fullStr | Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China |
| title_full_unstemmed | Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China |
| title_short | Biochemical and molecular features of chinese patients with glutaric acidemia type 1 from Fujian Province, southeastern China |
| title_sort | biochemical and molecular features of chinese patients with glutaric acidemia type 1 from fujian province southeastern china |
| topic | Acylcarnitine profile GCDH Glutaric acidemia type 1 Southeastern China Variant |
| url | https://doi.org/10.1186/s13023-023-02833-z |
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