Long-term prognosis of 35 patients with methionine adenosyltransferase deficiency based on newborn screening in China
Methionine adenosyltransferase deficiency (MATD) is a rare metabolic disorder caused by mono- or biallelic MAT1A mutations that are not yet well understood. Of the 4,065,644 neonates screened between November 2010 and December 2021, 35 individuals have been diagnosed with an estimated incidence of 1...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.1059680/full |
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| author | Fan Tong Yuchen Zhang Yuchen Zhang Chi Chen Ling Zhu Yijun Lu Yijun Lu Zhanming Zhang Ting Chen Jiaxuan Yan Jing Zheng Xiaoxu Zhao Duo Zhou Xin Yang Rulai Yang Xiaohui Cang Xiaohui Cang Pingping Jiang Pingping Jiang Qiang Shu Qiang Shu |
| author_facet | Fan Tong Yuchen Zhang Yuchen Zhang Chi Chen Ling Zhu Yijun Lu Yijun Lu Zhanming Zhang Ting Chen Jiaxuan Yan Jing Zheng Xiaoxu Zhao Duo Zhou Xin Yang Rulai Yang Xiaohui Cang Xiaohui Cang Pingping Jiang Pingping Jiang Qiang Shu Qiang Shu |
| author_sort | Fan Tong |
| collection | DOAJ |
| description | Methionine adenosyltransferase deficiency (MATD) is a rare metabolic disorder caused by mono- or biallelic MAT1A mutations that are not yet well understood. Of the 4,065,644 neonates screened between November 2010 and December 2021, 35 individuals have been diagnosed with an estimated incidence of 1: 116,161 by a cutoff value of methionine 82.7 μmol/L and follow-up over 11 years. MATD patients with autosomal recessive (AR) type had higher clinical and genetic heterogeneity than those with autosomal dominant (AD) type. Fifteen unrelated AD patients harbored one well-known dominant variant, c.791 G>A or c.776 C>T, and were clinically unaffected with a mean plasma methionine (Met) value <300 μmol/L. Twenty AR cases have unique genotypes and presented a wide range of clinical abnormalities from asymptomatic to white matter lesions. Of them, 10 AR patients displayed severe manifestations, such as verbal difficulty, motor delay, development delay, and white matter lesions, with mean Met >500 μmol/L and thereby were treated with a methionine-restricted diet alone or in combination with betaine, folate, or vitamin B6, and were healthy finally. Neurological abnormalities were evidenced in two patients (P16 and P27) with Met values >800 μmol/L by MRI scan. Neurological abnormalities were reversed here by liver transplantation or by the determination of S-adenosylmethionine supplementation. Additionally, 38 variants of MAT1A were distributed within patients and carriers, of which 24 were novel and mostly predicted to be damaged. Our findings with an extensive clinical and genetic dataset provided new insights into its diagnosis and treatment and will be helpful for its optimal management in the future. |
| first_indexed | 2024-04-10T23:50:19Z |
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| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-10T23:50:19Z |
| publishDate | 2023-01-01 |
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| spelling | doaj.art-80acc5aa6019472ca8a3e1d768b4972a2023-01-10T18:48:41ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-01-011010.3389/fcell.2022.10596801059680Long-term prognosis of 35 patients with methionine adenosyltransferase deficiency based on newborn screening in ChinaFan Tong0Yuchen Zhang1Yuchen Zhang2Chi Chen3Ling Zhu4Yijun Lu5Yijun Lu6Zhanming Zhang7Ting Chen8Jiaxuan Yan9Jing Zheng10Xiaoxu Zhao11Duo Zhou12Xin Yang13Rulai Yang14Xiaohui Cang15Xiaohui Cang16Pingping Jiang17Pingping Jiang18Qiang Shu19Qiang Shu20Department of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaInstitute of Genetics, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaInstitute of Genetics, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaInstitute of Genetics, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaInstitute of Genetics, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaInstitute of Genetics, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Genetics and Metabolism, The Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Molecular Genetics, University of Toronto, Toronto, ON, CanadaMethionine adenosyltransferase deficiency (MATD) is a rare metabolic disorder caused by mono- or biallelic MAT1A mutations that are not yet well understood. Of the 4,065,644 neonates screened between November 2010 and December 2021, 35 individuals have been diagnosed with an estimated incidence of 1: 116,161 by a cutoff value of methionine 82.7 μmol/L and follow-up over 11 years. MATD patients with autosomal recessive (AR) type had higher clinical and genetic heterogeneity than those with autosomal dominant (AD) type. Fifteen unrelated AD patients harbored one well-known dominant variant, c.791 G>A or c.776 C>T, and were clinically unaffected with a mean plasma methionine (Met) value <300 μmol/L. Twenty AR cases have unique genotypes and presented a wide range of clinical abnormalities from asymptomatic to white matter lesions. Of them, 10 AR patients displayed severe manifestations, such as verbal difficulty, motor delay, development delay, and white matter lesions, with mean Met >500 μmol/L and thereby were treated with a methionine-restricted diet alone or in combination with betaine, folate, or vitamin B6, and were healthy finally. Neurological abnormalities were evidenced in two patients (P16 and P27) with Met values >800 μmol/L by MRI scan. Neurological abnormalities were reversed here by liver transplantation or by the determination of S-adenosylmethionine supplementation. Additionally, 38 variants of MAT1A were distributed within patients and carriers, of which 24 were novel and mostly predicted to be damaged. Our findings with an extensive clinical and genetic dataset provided new insights into its diagnosis and treatment and will be helpful for its optimal management in the future.https://www.frontiersin.org/articles/10.3389/fcell.2022.1059680/fullmethionine adenosyltransferase deficiency (MATD)long-term prognosisMAT1Aneurological deficitshypermethioninemiaS-adenosylmethionine |
| spellingShingle | Fan Tong Yuchen Zhang Yuchen Zhang Chi Chen Ling Zhu Yijun Lu Yijun Lu Zhanming Zhang Ting Chen Jiaxuan Yan Jing Zheng Xiaoxu Zhao Duo Zhou Xin Yang Rulai Yang Xiaohui Cang Xiaohui Cang Pingping Jiang Pingping Jiang Qiang Shu Qiang Shu Long-term prognosis of 35 patients with methionine adenosyltransferase deficiency based on newborn screening in China Frontiers in Cell and Developmental Biology methionine adenosyltransferase deficiency (MATD) long-term prognosis MAT1A neurological deficits hypermethioninemia S-adenosylmethionine |
| title | Long-term prognosis of 35 patients with methionine adenosyltransferase deficiency based on newborn screening in China |
| title_full | Long-term prognosis of 35 patients with methionine adenosyltransferase deficiency based on newborn screening in China |
| title_fullStr | Long-term prognosis of 35 patients with methionine adenosyltransferase deficiency based on newborn screening in China |
| title_full_unstemmed | Long-term prognosis of 35 patients with methionine adenosyltransferase deficiency based on newborn screening in China |
| title_short | Long-term prognosis of 35 patients with methionine adenosyltransferase deficiency based on newborn screening in China |
| title_sort | long term prognosis of 35 patients with methionine adenosyltransferase deficiency based on newborn screening in china |
| topic | methionine adenosyltransferase deficiency (MATD) long-term prognosis MAT1A neurological deficits hypermethioninemia S-adenosylmethionine |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.1059680/full |
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