Methionine Adenosyltransferase I/III Deficiency Detected by Newborn Screening
Methionine adenosyltransferase I/III deficiency is an inborn error of metabolism due to mutations in the <i>MAT1A</i> gene. It is the most common cause of hypermethioninemia in newborn screening. Heterozygotes are often asymptomatic. In contrast, homozygous or compound heterozygous indiv...
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MDPI AG
2022-06-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/7/1163 |
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| author | Vanessa Hübner Luciana Hannibal Nils Janzen Sarah Catharina Grünert Peter Freisinger |
| author_facet | Vanessa Hübner Luciana Hannibal Nils Janzen Sarah Catharina Grünert Peter Freisinger |
| author_sort | Vanessa Hübner |
| collection | DOAJ |
| description | Methionine adenosyltransferase I/III deficiency is an inborn error of metabolism due to mutations in the <i>MAT1A</i> gene. It is the most common cause of hypermethioninemia in newborn screening. Heterozygotes are often asymptomatic. In contrast, homozygous or compound heterozygous individuals can develop severe neurological symptoms. Less than 70 cases with biallelic variants have been reported worldwide. A methionine-restricted diet is recommended if methionine levels are above 500–600 µmol/L. In this study, we report on a female patient identified with elevated methionine concentrations in a pilot newborn screening program. The patient carries a previously described variant c.1132G>A (p.Gly378Ser) in homozygosity. It is located at the C-terminus of MAT1A. In silico analysis suggests impaired protein stability by β-turn disruption. On a methionine-restricted diet, her serum methionine concentration ranged between 49–605 µmol/L (median 358 µmol/L). Her clinical course was characterized by early-onset muscular hypotonia, mild developmental delay, delayed myelination and mild periventricular diffusion interference in MRI. At 21 months, the girl showed age-appropriate neurological development, but progressive diffusion disturbances in MRI. Little is known about the long-term outcome of this disorder and the necessity of treatment. Our case demonstrates that neurological symptoms can be transient and even patients with initial neurologic manifestations can show normal development under dietary management. |
| first_indexed | 2024-03-09T03:23:35Z |
| format | Article |
| id | doaj.art-7d981b32621d4f6f95bb5025bab002d2 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T03:23:35Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-7d981b32621d4f6f95bb5025bab002d22023-12-03T15:05:43ZengMDPI AGGenes2073-44252022-06-01137116310.3390/genes13071163Methionine Adenosyltransferase I/III Deficiency Detected by Newborn ScreeningVanessa Hübner0Luciana Hannibal1Nils Janzen2Sarah Catharina Grünert3Peter Freisinger4Department of Pediatrics, Metabolic Disease Center, Klinikum Reutlingen, Steinenbergstr. 31, 72764 Reutlingen, GermanyDepartment of General Pediatrics, Adolescent Medicine and Neonatology, University Medical Center, Faculty of Medicine, University of Freiburg, Mathildenstraße 1, 79106 Freiburg, GermanyScreening Laboratory Hannover, Box 91 10 09, 30430 Hannover, GermanyDepartment of General Pediatrics, Adolescent Medicine and Neonatology, University Medical Center, Faculty of Medicine, University of Freiburg, Mathildenstraße 1, 79106 Freiburg, GermanyDepartment of Pediatrics, Metabolic Disease Center, Klinikum Reutlingen, Steinenbergstr. 31, 72764 Reutlingen, GermanyMethionine adenosyltransferase I/III deficiency is an inborn error of metabolism due to mutations in the <i>MAT1A</i> gene. It is the most common cause of hypermethioninemia in newborn screening. Heterozygotes are often asymptomatic. In contrast, homozygous or compound heterozygous individuals can develop severe neurological symptoms. Less than 70 cases with biallelic variants have been reported worldwide. A methionine-restricted diet is recommended if methionine levels are above 500–600 µmol/L. In this study, we report on a female patient identified with elevated methionine concentrations in a pilot newborn screening program. The patient carries a previously described variant c.1132G>A (p.Gly378Ser) in homozygosity. It is located at the C-terminus of MAT1A. In silico analysis suggests impaired protein stability by β-turn disruption. On a methionine-restricted diet, her serum methionine concentration ranged between 49–605 µmol/L (median 358 µmol/L). Her clinical course was characterized by early-onset muscular hypotonia, mild developmental delay, delayed myelination and mild periventricular diffusion interference in MRI. At 21 months, the girl showed age-appropriate neurological development, but progressive diffusion disturbances in MRI. Little is known about the long-term outcome of this disorder and the necessity of treatment. Our case demonstrates that neurological symptoms can be transient and even patients with initial neurologic manifestations can show normal development under dietary management.https://www.mdpi.com/2073-4425/13/7/1163MAT1Ahypermethioninemiamethionine adenosyltransferasenewborn screeningCNS symptoms |
| spellingShingle | Vanessa Hübner Luciana Hannibal Nils Janzen Sarah Catharina Grünert Peter Freisinger Methionine Adenosyltransferase I/III Deficiency Detected by Newborn Screening Genes MAT1A hypermethioninemia methionine adenosyltransferase newborn screening CNS symptoms |
| title | Methionine Adenosyltransferase I/III Deficiency Detected by Newborn Screening |
| title_full | Methionine Adenosyltransferase I/III Deficiency Detected by Newborn Screening |
| title_fullStr | Methionine Adenosyltransferase I/III Deficiency Detected by Newborn Screening |
| title_full_unstemmed | Methionine Adenosyltransferase I/III Deficiency Detected by Newborn Screening |
| title_short | Methionine Adenosyltransferase I/III Deficiency Detected by Newborn Screening |
| title_sort | methionine adenosyltransferase i iii deficiency detected by newborn screening |
| topic | MAT1A hypermethioninemia methionine adenosyltransferase newborn screening CNS symptoms |
| url | https://www.mdpi.com/2073-4425/13/7/1163 |
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