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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2013/10/22 17:50:32」(JST)
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Hypermethioninemia |
Classification and external resources |
Methionine
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ICD-10 |
E72.1 |
ICD-9 |
270.4 |
DiseasesDB |
34424 |
Hypermethioninemia is an excess of the amino acid methionine, in the blood. This condition can occur when methionine is not broken down properly in the body.
Contents
- 1 Diagnosis
- 2 Pathophysiology
- 3 Inheritance
- 4 See also
- 5 General references
Diagnosis[edit]
People with hypermethioninemia often do not show any symptoms. Some individuals with hypermethioninemia exhibit learning disabilities, mental retardation, and other neurological problems; delays in motor skills such as standing or walking; sluggishness; muscle weakness; liver problems; unusual facial features; and their breath, sweat, or urine may have a smell resembling boiled cabbage.
Hypermethioninemia can occur with other metabolic disorders, such as homocystinuria, tyrosinemia and galactosemia, which also involve the faulty breakdown of particular molecules. It can also result from liver disease or excessive dietary intake of methionine from consuming large amounts of protein or a methionine-enriched infant formula.
Pathophysiology[edit]
Inherited hypermethioninemia that is not associated with other metabolic disorders can be caused by shortages in the enzymes that break down methionine. These enzymes are produced from the MAT1A, GNMT and AHCY genes. The reactions involved in metabolizing methionine help supply some of the amino acids needed for protein production. These reactions are also involved in transferring methyl groups, consisting of a carbon atom and three hydrogen atoms, from one molecule to another (transmethylation), which is important in many cellular processes.
- The MAT1A gene provides instructions for producing the enzyme methionine adenosyltransferase. This enzyme converts methionine into a compound called S-adenosylmethionine.
- The GNMT gene provides instructions for making the enzyme glycine N-methyltransferase. This enzyme starts the next step in the process, converting S-adenosylmethionine to a compound called S-adenosyl homocysteine.
- The AHCY gene provides instructions for producing the enzyme S-adenosylhomocysteine hydrolase. This enzyme converts the S-adenosyl homocysteine into the compound homocysteine. Homocysteine may be converted back to methionine or into another amino acid, cysteine.
A deficiency of any of these enzymes results in a buildup of methionine in the body, and may cause signs and symptoms related to hypermethioninemia.
Inheritance[edit]
Hypermethioninemia can have different inheritance patterns. This condition is usually inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.
Hypermethioninemia is occasionally inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, an affected person usually has one parent with the condition.
See also[edit]
- List of amino acid metabolism disorders
General references[edit]
- National Library of Medicine. Hypermethioninemia
Inborn error of amino acid metabolism (E70–E72, 270)
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K→acetyl-CoA |
Lysine/straight chain
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- Glutaric acidemia type 1
- type 2
- Hyperlysinemia
- Pipecolic acidemia
- Saccharopinuria
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Leucine
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- 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
- 3-Methylcrotonyl-CoA carboxylase deficiency
- 3-Methylglutaconic aciduria 1
- Isovaleric acidemia
- Maple syrup urine disease
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Tryptophan
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G |
G→pyruvate→citrate
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Glycine
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- D-Glyceric acidemia
- Glutathione synthetase deficiency
- Sarcosinemia
- Glycine→Creatine: GAMT deficiency
- Glycine encephalopathy
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G→glutamate→
α-ketoglutarate
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Histidine
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- Carnosinemia
- Histidinemia
- Urocanic aciduria
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Proline
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- Hyperprolinemia
- Prolidase deficiency
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Glutamate/glutamine
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G→propionyl-CoA→
succinyl-CoA
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Valine
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- Hypervalinemia
- Isobutyryl-CoA dehydrogenase deficiency
- Maple syrup urine disease
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Isoleucine
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- 2-Methylbutyryl-CoA dehydrogenase deficiency
- Beta-ketothiolase deficiency
- Maple syrup urine disease
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Methionine
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- Cystathioninuria
- Homocystinuria
- Hypermethioninemia
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General BC/OA
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- Methylmalonic acidemia
- Methylmalonyl-CoA mutase deficiency
- Propionic acidemia
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G→fumarate
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Phenylalanine/tyrosine
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Phenylketonuria
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- 6-Pyruvoyltetrahydropterin synthase deficiency
- Tetrahydrobiopterin deficiency
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Tyrosinemia
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- Alkaptonuria/Ochronosis
- Type I tyrosinemia
- Type II tyrosinemia
- Type III tyrosinemia/Hawkinsinuria
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Tyrosine→Melanin
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- Albinism: Ocular albinism (1)
- Oculocutaneous albinism (Hermansky–Pudlak syndrome)
- Waardenburg syndrome
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Tyrosine→Norepinephrine
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- Dopamine beta hydroxylase deficiency
- reverse: Brunner syndrome
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G→oxaloacetate
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Urea cycle/Hyperammonemia
(arginine
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- Argininemia
- Argininosuccinic aciduria
- Carbamoyl phosphate synthetase I deficiency
- Citrullinemia
- N-Acetylglutamate synthase deficiency
- Ornithine transcarbamylase deficiency/translocase deficiency
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Transport/
IE of RTT |
- Solute carrier family: Cystinuria
- Hartnup disease
- Iminoglycinuria
- Lysinuric protein intolerance
- Fanconi syndrome: Oculocerebrorenal syndrome
- Cystinosis
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Other |
- 2-Hydroxyglutaric aciduria
- Aminoacylase 1 deficiency
- Ethylmalonic encephalopathy
- Fumarase deficiency
- Trimethylaminuria
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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UpToDate Contents
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English Journal
- Thirteen Patients with MAT1A Mutations Detected Through Newborn Screening: 13 Years' Experience.
- Chadwick S, Fitzgerald K, Weiss B, Ficicioglu C.Author information The Children's Hospital of Philadelphia, Section of Metabolism, Perelman School of Medicine at the University of Pennsylvania, 3501 Civic Center blvd #9054, Philadelphia, PA, 19106, USA.AbstractBackground: Methionine adenosyltransferase I/III (MATI/III) deficiency is the most common genetic cause of persistent isolated hypermethioninemia. Patients and Methods : This is a retrospective data analysis of 62 newborns with elevated methionine detected by newborn screening between January 2000 and June 2013. The clinical, biochemical, and molecular findings of a subset of these children with MAT1A mutations associated with MATI/III deficiency are presented. Results: Of the 62 newborns with elevated methionine, 12 were identified as having classical homocystinuria; 37 were false-positives; and 13 were found to have isolated persistent hypermethioninemia in the absence of biochemical markers of homocystinuria, abnormal liver function studies, or other causes of elevated methionine. These 13 individuals underwent genetic testing for changes in the MAT1A gene, associated with MATI/III deficiency. Three of 13 were found to have the common autosomal dominant R264H mutation, one was found to be a compound heterozygote for two novel pathogenic mutations, and three were found to be heterozygotes for previously reported mutations shown to cause autosomal recessive MATI/III deficiency when present in homozygous or a compound heterozygous configuration. The remaining six patients had variants of unknown clinical significance or novel mutations. For the majority of individuals, methionine persisted above the normal range but trended downward over time. None of these 13 individuals was started on a low-methionine diet, and all have age-appropriate growth and development. Conclusion: These cases show that individuals with even single changes in the MAT1A gene may have elevations in methionine identified by newborn screening, which may persist for months after birth without any clinical consequences.
- JIMD reports.JIMD Rep.2014 Jan 21. [Epub ahead of print]
- Background: Methionine adenosyltransferase I/III (MATI/III) deficiency is the most common genetic cause of persistent isolated hypermethioninemia. Patients and Methods : This is a retrospective data analysis of 62 newborns with elevated methionine detected by newborn screening between January 2000 a
- PMID 24445979
- White matter changes in an untreated, newly diagnosed case of classical homocystinuria.
- Brenton JN, Matsumoto JA, Rust RS, Wilson WG.Author information 1University of Virginia, Charlottesville, VA, USA.AbstractThe authors report the case of a 4-year-old boy who developed progressive unilateral weakness and developmental delays prior to his diagnosis of classical homocystinuria. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse white matter changes, raising the concern for a secondary diagnosis causing leukoencephalopathy, since classical homocystinuria is not typically associated with these changes. Other inborn errors of the transsulfuration pathway have been reported as causing these changes. Once begun on therapy for his homocystinuria, his neurologic deficits resolved and his delays rapidly improved. Repeat MRI performed one year after instating therapy showed resolution of his white matter abnormalities. This case illustrates the need to consider homocystinuria and other amino acidopathies in the differential diagnosis of childhood white matter diseases and lends weight to the hypothesis that hypermethioninemia may induce white matter changes.
- Journal of child neurology.J Child Neurol.2014 Jan;29(1):88-92. doi: 10.1177/0883073812465012. Epub 2012 Nov 15.
- The authors report the case of a 4-year-old boy who developed progressive unilateral weakness and developmental delays prior to his diagnosis of classical homocystinuria. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse white matter changes, raising the concern for a secondary diag
- PMID 23155204
- Spectrum of mutations associated with methionine adenosyltransferase I/III deficiency among individuals identified during newborn screening in Japan.
- Nagao M, Tanaka T, Furujo M.Author information Department of Pediatrics and Clinical research, National Hospital Organization Hokkaido Medical Center, Sapporo, Japan. Electronic address: nagaom@hok-mc.hosp.go.jp.AbstractMethionine adenosyltransferase I/III deficiency (MAT I/III deficiency) is an inborn error of metabolism that results in isolated persistent hypermethioninemia. Definitive diagnosis is now possible by molecular analyses of the MAT1A gene. Based on newborn screening (NBS) data collected between 2001 and 2012 in Hokkaido, Japan, the estimated incidence of MAT I/III deficiency was 1 in 107,850. 24 patients (13 males, 11 females) from 11 prefectures in Japan were referred to our laboratory for genetic diagnosis of MAT I/III deficiency. They were all found between 1992 and 2012 by the NBS program in each region. In these 24 individuals, we identified 12 distinct mutations; 14 patients were heterozygous for an R264H mutation; R264H caused an autosomal dominant and clinically benign phenotype in each case. The mutations in the other 10 patients showed autosomal recessive inheritance and included eight novel MAT1A mutations. Putative amino acid substitutions at R356 were observed with six alleles (three R356P, two R356Q, and one R356L). MAT I/III deficiency is not always benign because three of our cases involved brain demyelination or neurological complications. DNA testing early in life is recommended to prevent potential detrimental neurological manifestations.
- Molecular genetics and metabolism.Mol Genet Metab.2013 Dec;110(4):460-4. doi: 10.1016/j.ymgme.2013.10.013. Epub 2013 Oct 31.
- Methionine adenosyltransferase I/III deficiency (MAT I/III deficiency) is an inborn error of metabolism that results in isolated persistent hypermethioninemia. Definitive diagnosis is now possible by molecular analyses of the MAT1A gene. Based on newborn screening (NBS) data collected between 2001 a
- PMID 24231718
Japanese Journal
- Spectrum of hypermethioninemia in Taiwan
- CHIEN Yin-Hsiu,MUDD S. Harvey,LEE Ni-Chung,HUANG Ai-Chu,HWU Wuh-Liang
- 日本先天代謝異常学会雑誌 24(1), 66-70, 2008-08-13
- NAID 10029094741
- Spectrum of hypermethioninemia in Taiwan
- CHIEN Yin-Hsiu,MUDD S. Harvey,HWU Wuh-Liang,HUANG Ai-Chu,LEE Ni-Chung
- 日本先天代謝異常学会雑誌 23(1), 214-215, 2007-10-23
- NAID 10019771766
- Soy protein diet prevents hypermethioninemia caused by portacaval shunt in rats
- Shimooka Rie,Yasuhiro Kido,Chiba Naoko
- The journal of medical investigation : JMI 53(3/4), 255-263, 2006-08
- NAID 110004755684
Related Links
- Hypermethioninemia can have different inheritance patterns. This condition is usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents ...
- Most individuals with hypermethioninemia (MET) do not show any signs. If your baby does show signs of MET, you may notice: Developmental delays Sleeping longer or more often Weak muscle tone (known as hypotonia) A ...
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