Hypermethioninemia

mutation in GNMT, MAT1A, AHCY

Also Known As:

Deficiency of Methionine Adenosyltransferase; GNMT Deficiency; Glycine N-Methyltransferase Deficiency; Hepatic Methionine Adenosyltransferase Deficiency; Hypermethioninemia with Deficiency of S-Adenosylhomocysteine Hydrolase; Hypermethioninemia, Isolated Persistent; Methionine Adenosyltransferase Deficiency; Methioninemia; S-Adenosylhomocysteine Hydrolase Deficiency

Networked: 136 relevant articles (2 outcomes, 13 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hyperhomocysteinemia
2.	Homocystinuria
3.	Necrosis
4.	Edema (Dropsy)
5.	Tyrosinemias (Tyrosinemia)

Experts

1.	Wyse, Angela T S: 15 articles (08/2020 - 11/2005)
2.	Stefanello, Francieli M: 8 articles (04/2020 - 11/2005)
3.	Wagner, Conrad: 7 articles (02/2016 - 05/2003)
4.	Spanevello, Roselia Maria: 6 articles (05/2021 - 10/2017)
5.	Stefanello, Francieli Moro: 6 articles (05/2021 - 10/2017)
6.	Blom, Henk J: 6 articles (03/2020 - 10/2011)
7.	Spohr, Luiza: 5 articles (05/2021 - 09/2018)
8.	Soares, Mayara Sandrielly Pereira: 5 articles (12/2020 - 10/2017)
9.	Allen, Robert H: 5 articles (01/2017 - 05/2003)
10.	Chien, Yin-Hsiu: 5 articles (01/2017 - 06/2005)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Hypermethioninemia:

1.	Methionine (L-Methionine)FDA Link 06/01/2005 - "Although most of the patients with isolated hypermethioninemia were put on diet in this study, their IQ scores were not related to either the initial or follow-up plasma methionine levels. " 09/01/1977 - "Using these techniques, it was possible to study the urinary elimination of this secondary metabolite of methionine in normal children, homocystinurics and in one case of hypermethioninemia. " 06/01/2019 - "Methionine S-adenosyltransferase deficiency, due to mutations in MAT1A , is the most common cause of persistent isolated hypermethioninemia (PIH). " 11/01/2016 - "Hypermethioninemia is a condition defined as elevated plasma methionine levels and may be a consequence of different conditions that include non-genetic and genetic causes. " 11/01/2012 - "Methionine restriction can be an additional therapeutic strategy because hypermethioninemia alone may be neurotoxic; however, lowering methionine carries a risk to decrease the synthesis of SAM."
2.	Betaine (C.B.B.)FDA Link 11/14/2022 - "In contrast, in pnrCBS deficiency, betaine doses higher than 100 mg/kg/day could be harmful to these patients with pre-existing hypermethioninemia. " 09/22/2020 - "OT-58 markedly reduced both hyperhomocysteinemia and hypermethioninemia caused by the diets and betaine in HCU mice. " 03/01/2020 - "Brain edema has also been observed in individuals with severe hypermethioninemia without concomitant betaine supplementation. " 09/22/2020 - "Betaine was less effective in lowering tHcy on the background of normal or increased methionine intake, while exacerbating hypermethioninemia. " 02/08/2022 - "Betaine Supplementation Attenuates S-Adenosylhomocysteine Hydrolase-Deficiency-Accelerated Atherosclerosis in Apolipoprotein E-Deficient Mice."
3.	Adenosine Triphosphatases (ATPase)IBA 11/01/2019 - "Results showed that gestational hypermethioninemia diminished Na+,K+-ATPase activity and sulfhydryl content and increased DNA damage at 21 and 30 days of life. " 03/01/2014 - "Development of an animal model for gestational hypermethioninemia in rat and its effect on brain Na⁺,K⁺-ATPase/Mg²⁺-ATPase activity and oxidative status of the offspring." 06/01/2007 - "Effect of hypermethioninemia on some parameters of oxidative stress and on Na(+),K (+)-ATPase activity in hippocampus of rats." 11/01/2005 - "These findings suggest that reduction of Na+,K+-ATPase activity and induction of oxidative stress may be involved in the brain damage observed in human hypermethioninemia." 07/01/2018 - "S-Adenosylmethionine Promotes Oxidative Stress and Decreases Na+, K+-ATPase Activity in Cerebral Cortex Supernatants of Adolescent Rats: Implications for the Pathogenesis of S-Adenosylhomocysteine Hydrolase Deficiency."
4.	Thiobarbituric Acid Reactive SubstancesIBA 11/01/2007 - "We also showed that Na+,K+-ATPase activity and TBARS were changed in cerebral cortex of rats subjected to hypermethioninemia. " 06/01/2007 - "Results showed that rats subjected to acute hypermethioninemia presented a reduction of Na(+),K(+)-ATPase activity and an increase in TBARS when the animals were killed at 3 and 12 h, but not at 1 h, after methionine administration. " 06/01/2007 - "Since chronic hypermethioninemia altered TBARS and Na(+),K(+)-ATPase activity at 12 h after methionine administration, we also investigated the effect of acute administration of this amino acid on the same parameters studied after chronic methionine administration. " 06/01/2007 - "Results showed that chronic hypermethioninemia significantly increased TBARS, decreased Na(+),K(+)-ATPase activity but did not alter catalase and total thiol content. " 06/01/2007 - "In the present study we investigated the effect of chronic administration of methionine, a metabolite accumulated in many inherited pathological conditions such as methionine adenosyltransferase deficiency and homocystinuria, on some parameters of oxidative stress, namely thiobarbituric acid reactive substances (TBARS), catalase activity and total thiol content, as well as on Na(+),K(+)-ATPase activity in rat hippocampus. "
5.	CatalaseIBA 03/01/2014 - "Maternal hypermethioninemia also decreased the activities of Na(+),K(+)-ATPase, Mg(2+)-ATPase and catalase, as well as reduced total sulfhydryl content in the encephalon of the pups. " 08/01/2009 - "Results showed that hypermethioninemia increased chemiluminescence, carbonyl content and glutathione peroxidase activity, decreased total antioxidant potential, as well as altered catalase activity. " 06/01/2007 - "Results showed that chronic hypermethioninemia significantly increased TBARS, decreased Na(+),K(+)-ATPase activity but did not alter catalase and total thiol content. " 06/01/2007 - "In the present study we investigated the effect of chronic administration of methionine, a metabolite accumulated in many inherited pathological conditions such as methionine adenosyltransferase deficiency and homocystinuria, on some parameters of oxidative stress, namely thiobarbituric acid reactive substances (TBARS), catalase activity and total thiol content, as well as on Na(+),K(+)-ATPase activity in rat hippocampus. " 03/01/2014 - "In the present study we developed a chemically induced experimental model for gestational hypermethioninemia in rats and evaluated in the offspring the activities of Na(+),K(+)-ATPase and Mg(2+)-ATPase, as well as oxidative stress parameters, namely sulfhydryl content, thiobarbituric acid-reactive substances and the antioxidant enzymes superoxide dismutase and catalase in encephalon. "
6.	AcetylcholinesteraseIBA 05/01/2021 - "The aim of this study was to analyze the redox status and acetylcholinesterase (AChE) activity in the hippocampus, striatum, and cerebellum of young Wistar rats subjected to an acute hypermethioninemia protocol. " 11/01/2007 - "In the present study we investigated the effect of chronic hypermethioninemia on rat performance in the Morris water maze task, as well as on acetylcholinesterase (AChE) activity in rat cerebral cortex. " 05/01/2021 - "Acute hypermethioninemia impairs redox homeostasis and acetylcholinesterase activity in the hippocampus, striatum, and cerebellum of young rats." 11/01/2007 - "Hypermethioninemia increases cerebral acetylcholinesterase activity and impairs memory in rats."
7.	Amino Acids FDA Link 08/01/2020 - "However, the increased levels of this amino acid in plasma, a condition known as hypermethioninemia, can lead to cell alterations. " 10/01/2017 - "Patients with hypermethioninemia can present neurological dysfunction; however, the neurotoxicity mechanisms induced by these amino acids remain unknown. " 08/01/2006 - "These effects of a SPI diet may be due to its amino acid composition, since an amino acid mixture diet mimicking a 40% SPI-M diet was also effective to hypermethioninemia of PCS rats. " 01/01/2019 - "The cell viability assay further supported the hypothesis that aggregation of single amino acid may contribute to the etiology of metabolic disorders like cystinuria and hypermethioninemia. " 01/08/2015 - "Evidence that these variants predispose individuals to thoracic aortic aneurysms and dissections includes the following: there is a paucity of rare variants in MAT2A in the population; amino acids Glu344 and Arg356 are conserved from humans to zebrafish; and substitutions of these amino acids in MAT Iα are found in individuals with hypermethioninemia. "
8.	Methionine AdenosyltransferaseIBA 08/01/2022 - "Methionine adenosyltransferase (MAT) I/III deficiency is the most common cause of hypermethioninemia. " 04/01/2019 - "Methionine adenosyltransferase I/III (MAT I/III) deficiency is characterized by persistent hypermethioninemia. " 01/01/2014 - "Methionine adenosyltransferase I/III (MATI/III) deficiency is the most common genetic cause of persistent isolated hypermethioninemia. " 12/01/2013 - "Methionine adenosyltransferase I/III deficiency (MAT I/III deficiency) is an inborn error of metabolism that results in isolated persistent hypermethioninemia. " 11/01/2012 - "Methionine adenosyltransferase I/III (MAT I/III) deficiency, caused by mutations in the MAT1A gene, is an inherited metabolic disorder characterized by persistent hypermethioninemia, usually detected by newborn mass screening. "
9.	HomocysteineIBA 01/01/2015 - "This latter condition is biochemically characterized by isolated persistent hypermethioninemia, accompanied in some individuals with slightly elevated levels of homocysteine in plasma. " 02/15/2011 - "Hypermethioninemia is due chiefly to remethylation of the accumulated homocysteine. " 08/20/2010 - "Because Cbs(-/-) mice display hyperhomocysteinemia and hypermethioninemia, our results raise questions against the homocysteine-based etiology of CBS deficiency and the current newborn screening for homocysteinemia using Guthrie's method, which detects hypermethioninemia." 01/01/2022 - "The above increase in oxidative stress could be directly caused by an increase in the blood levels of methionine (hypermethioninemia) or one of its metabolites, such as homocysteine. " 01/28/2020 - "Among these, the disease caused by methionine adenosyltransferase (MAT) I/III deficiency is the most common, and is characterized by persistent, isolated hypermethioninemia as well as slightly elevated homocysteine. "
10.	EnzymesIBA 01/01/2023 - "Chemical hypermethioninemia in young mice: oxidative damage and reduction of antioxidant enzyme activity in brain, kidney, and liver." 06/01/2020 - "Methionine adenosyltransferase (MAT) deficiency, characterized by isolated persistent hypermethioninemia (IPH), is caused by mutations in the MAT1A gene encoding MATαl, one of the major hepatic enzymes. " 01/01/2019 - "In addition, mutation of Arg264 in MATα1 causes isolated persistent hypermethioninemia, which is characterized by low activity of the enzyme in liver and high level of plasma methionine. " 06/01/2011 - "Results showed that administration of antioxidants partially prevented the inhibition of enzyme activity caused by acute and chronic hypermethioninemia. " 03/01/1997 - "Methionine adenosyltransferase (MAT) I/III deficiency, characterized by isolated persistent hypermethioninemia, is caused by mutations in the MAT1A gene encoding MAT(alpha)1, the subunit of major hepatic enzymes MAT I ([alpha1]4) and III([alpha1]2). "

Therapies and Procedures

1.	Therapeutics 01/01/2005 - "S-Adenosylhomocysteine hydrolase deficiency: a second patient, the younger brother of the index patient, and outcomes during therapy." 01/01/2020 - "We evaluated the impact of hypermethioninemia together with hyperhomocysteinemia on murine HCU phenotype and compared the efficacy of the current and novel therapies for HCU. " 08/15/1996 - "Therefore, a DNA-based diagnosis should be performed for individuals with isolated hypermethioninemia to assess if therapy aimed at the prevention of neurological manifestations is warranted." 06/01/2011 - "These data strongly suggest the oxidative damage as one possible mechanism involved in the reduction of Na(+),K(+)-ATPase activity caused by hypermethioninemia and if confirmed in human beings, we might propose the use of antioxidants as an adjuvant therapy in hypermethioninemic patients." 12/01/2015 - "Herein, we report reversible CWMLs associated with hypermethioninemia caused by poor protein restriction and betaine therapy in a 21-year-old male with pyridoxine-nonresponsive CBS deficiency. "
2.	Oral Administration 10/01/1992 - "In a placebo-controlled study, we measured the fasting plasma levels of sulphur-containing amino-acids in cirrhotic patients with hypermethioninemia and/or severe hepatocellular failure, during treatment with exogenous SAMe (1.2 g i.v. for 3 days, followed by an oral administration of 1.2 g for an additional 30 days; 8 cases) or saline and placebo tablets (8 cases). "
3.	Liver Transplantation 09/01/2015 - "Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiency."
4.	Surgical Portacaval Shunt (Portacaval Anastomosis) 08/01/2006 - "Soy protein diet prevents hypermethioninemia caused by portacaval shunt in rats."
5.	Enteral Nutrition (Feeding, Tube) 01/01/2018 - "In case of contraindication to enteral nutrition, compounded PN will be required, as described in this paper, to ensure adequate low amounts of methionine and others essential amino acids and avoid potentially fatal toxic hypermethioninemia. "