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Yinwang888 (talk | contribs) Added a newer reference and also broadened the scope of possible causes of the condition (it's not only due to vitamin B metabolism) Tags: Mobile edit Mobile web edit |
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{{Infobox medical condition (new)
| name = Hyperhomocysteinemia
| synonyms = '''Hyperhomocysteinaemia'''
| image = Plasma tHcy.svg
| caption = [[Homocysteine|Total plasma homocysteine]]
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'''Hyperhomocysteinemia''' is a medical condition characterized by an abnormally high level of [[homocysteine|total homocysteine]] (that is, including [[homocystine]] and homocysteine-cysteine disulfide) in the [[blood]], conventionally described as above 15 μmol/L.<ref>{{cite journal |pmid=19491420 |year=2009 |last1=Guo |first1=H |title=Influence of folic acid on plasma homocysteine levels & arterial endothelial function in patients with unstable angina |journal=The Indian Journal of Medical Research |volume=129 |issue=3 |pages=279–84 |last2=Chi |first2=J |last3=Xing |first3=Y |last4=Wang |first4=P }}</ref>
As a consequence of the biochemical reactions in which homocysteine is involved, deficiencies of
[[vitamin B6|vitamin B<sub>6</sub>]], [[folic acid]] (vitamin B<sub>9</sub>), and [[Cobalamin|vitamin B<sub>12</sub>]] can lead to high homocysteine levels.<ref name="Miller-p1033-9">{{cite journal |pmid=8172087 |year=1994 |last1=Miller |first1=J. W. |title=Vitamin B-6 deficiency vs folate deficiency: Comparison of responses to methionine loading in rats |journal=The American Journal of Clinical Nutrition |volume=59 |issue=5 |pages=1033–9 |last2=Nadeau |first2=M. R. |last3=Smith |first3=D |last4=Selhub |first4=J |doi=10.1093/ajcn/59.5.1033}}</ref>
Hyperhomocysteinemia is typically managed with vitamin B<sub>6</sub>, vitamin B<sub>9</sub> and vitamin B<sub>12</sub> supplementation.<ref name="ExpertOpPharm2001-Coen">{{cite journal |doi=10.1517/14656566.2.9.1449 |pmid=11585023 |title=Homocysteine-lowering treatment: An overview |journal=Expert Opinion on Pharmacotherapy |volume=2 |issue=9 |pages=1449–60 |year=2005 |last1=Stehouwer |first1=Coen DA |last2=Guldener |first2=Coen van |s2cid=45945199 }}</ref> Hyperhomocysteinemia is a risk factor for cardiovascular disease;
== Signs and symptoms ==
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=== Cardiovascular risks ===
Elevated homocysteine is a known risk factor for cardiovascular disease as well as [[thrombosis]].<ref>{{cite journal |pmid=10063987 |url=http://www.schattauer.de/index.php?id=1268&L=1&pii=th99020165&no_cache=1 |year=1999 |last1=Cattaneo |first1=Marco |title=Hyperhomocysteinemia, atherosclerosis and thrombosis |journal=Thrombosis and Haemostasis |volume=81 |issue=2 |pages=165–76 |doi=10.1055/s-0037-1614438 | s2cid=13228673 |access-date=2016-12-27 |archive-date=2018-07-21 |archive-url=https://web.archive.org/web/20180721145531/https://www.schattauer.de/index.php?id=1690 |url-status=dead }}</ref> It has also been shown to be associated with [[microalbuminuria]] which is a strong indicator of the risk of future cardiovascular disease and renal dysfunction.<ref>{{cite journal |doi=10.1161/01.ATV.21.1.74 |pmid=11145936 |title=Serum Homocysteine Levels Are Associated with the Development of (Micro)albuminuria : The Hoorn Study |journal=Arteriosclerosis, Thrombosis, and Vascular Biology |volume=21 |issue=1 |pages=74–81 |year=2001 |last1=Jager |first1=A. |last2=Kostense |first2=P. J. |last3=Nijpels |first3=G. |last4=Dekker |first4=J. M. |last5=Heine |first5=R. J. |last6=Bouter |first6=L. M. |last7=Donker |first7=A. J. M. |last8=Stehouwer |first8=C. D. A. |doi-access=free }}</ref> Homocysteine degrades and inhibits the formation of the three main structural components of [[arteries]]: [[collagen]], [[elastin]] and [[proteoglycans]]. In [[protein]]s, homocysteine permanently degrades cysteine [[disulfide bridges]] and lysine amino acid residues,<ref>{{cite journal |pmid=16702349 |year=2006 |last1=Jakubowski |first1=H |title=Pathophysiological consequences of homocysteine excess |journal=The Journal of Nutrition |volume=136 |issue=6 Suppl |pages=1741S–1749S |doi=10.1093/jn/136.6.1741S |doi-access=free }}</ref> affecting structure and function.
=== Neuropsychiatric illness ===
Evidence exists linking elevated homocysteine levels with [[vascular dementia]]<ref>{{Cite journal|last1=McVeigh|first1=Catherine|last2=Passmore|first2=Peter|date=September 2006|title=Vascular dementia: prevention and treatment|journal=Clinical Interventions in Aging|volume=1|issue=3|pages=229–235|issn=1176-9092|pmc=2695177|pmid=18046875|doi=10.2147/ciia.2006.1.3.229 |doi-access=free }}</ref> and [[Alzheimer's disease]].<ref>{{cite journal |doi=10.1016/s1474-4422(03)00438-1 |pmid=12849121 |title=Homocysteine and Alzheimer's disease |journal=The Lancet Neurology |volume=2 |issue=7 |pages=425–8 |year=2003 |last1=Morris |first1=Martha Savaria |s2cid=20443022 }}</ref><ref>{{cite journal |doi=10.1159/000326301 |pmid=21474939 |title=Folate and Homocysteine in the Cerebrospinal Fluid of Patients with Alzheimer's Disease or Dementia: A Case Control Study |journal=European Neurology |volume=65 |issue=5 |pages=270–8 |year=2011 |last1=Smach |first1=Mohamed Ali |last2=Jacob |first2=Nelly |last3=Golmard |first3=Jean-Louis |last4=Charfeddine |first4=Bassem |last5=Lammouchi |first5=Turkia |last6=Ben Othman |first6=Leila |last7=Dridi |first7=Hedi |last8=Bennamou |first8=Soufien |last9=Limem |first9=Khalifa |s2cid=7689901 }}</ref><ref>{{cite journal |doi=10.1371/journal.pone.0012244 |pmid=20838622 |pmc=2935890 |title=Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial |journal=PLOS ONE |volume=5 |issue=9 |pages=e12244 |year=2010 |last1=Smith |first1=A. David |last2=Smith |first2=Stephen M. |last3=De Jager |first3=Celeste A. |last4=Whitbread |first4=Philippa |last5=Johnston |first5=Carole |last6=Agacinski |first6=Grzegorz |last7=Oulhaj |first7=Abderrahim |last8=Bradley |first8=Kevin M. |last9=Jacoby |first9=Robin |last10=Refsum |first10=Helga |bibcode=2010PLoSO...512244S |doi-access=free }}</ref> There is also evidence that elevated homocysteine levels and low levels of vitamin B6 and B12 are risk factors for [[mild cognitive impairment]] and [[dementia]].<ref name="pmid19769453">{{cite journal |doi=10.1586/ern.09.75 |pmid=19769453 |title=Homocysteine, folate and vitamin B12in neuropsychiatric diseases: Review and treatment recommendations |journal=Expert Review of Neurotherapeutics |volume=9 |issue=9 |pages=1393–412 |year=2014 |last1=Stanger |first1=Olaf |last2=Fowler |first2=Brian |last3=Piertzik |first3=Klaus |last4=Huemer |first4=Martina |last5=Haschke-Becher |first5=Elisabeth |last6=Semmler |first6=Alexander |last7=Lorenzl |first7=Stefan |last8=Linnebank |first8=Michael |s2cid=13246020 |url=https://www.zora.uzh.ch/id/eprint/21178/1/DACH_Zora.pdf }}</ref> Oxidative stress induced by homocysteine may also play a role in [[schizophrenia]].<ref>{{cite journal |doi=10.1007/s11064-012-0707-3 |pmid=22270909 |pmc=3321271 |title=The Oxidative Stress May be Induced by the Elevated Homocysteine in Schizophrenic Patients |journal=Neurochemical Research |volume=37 |issue=5 |pages=1057–62 |year=2012 |last1=Dietrich-Muszalska |first1=Anna |last2=Malinowska |first2=Joanna |last3=Olas |first3=Beata |last4=Głowacki |first4=Rafal |last5=Bald |first5=Edward |last6=Wachowicz |first6=Barbara |last7=Rabe-Jabłońska |first7=Jolanta }}</ref>
=== Bone health ===
Elevated levels of homocysteine have also been linked to increased [[Fracture (bone)|fractures]] in elderly persons. Homocysteine auto-oxidizes and reacts with reactive oxygen intermediates, damaging endothelial cells and increasing the risk of [[thrombus]] formation.<ref>{{cite journal |doi=10.1056/NEJMoa032739 |pmid=15141042 |title=Homocysteine as a Predictive Factor for Hip Fracture in Older Persons |journal=New England Journal of Medicine |volume=350 |issue=20 |pages=2042–9 |year=2004 |last1=McLean |first1=Robert R. |last2=Jacques |first2=Paul F. |last3=Selhub |first3=Jacob |last4=Tucker |first4=Katherine L. |last5=Samelson |first5=Elizabeth J. |last6=Broe |first6=Kerry E. |last7=Hannan |first7=Marian T. |last8=Cupples |first8=L. Adrienne |last9=Kiel |first9=Douglas P. |s2cid=22853996 |
=== Ectopia lentis ===
[[Homocystinuria]] is the second most common cause of heritable [[ectopia lentis]]. Homocystinuria is an autosomal recessive metabolic disorder most often caused by a near absence of cystathionine b-synthetase. It is associated with intellectual disability, osteoporosis, chest deformities, and increased risk of thrombotic episodes. Lens dislocation occurs in 90% of patients, and is thought to be due to decreased zonular integrity due to the enzymatic defect. Lens dislocation in homocystinuria is usually bilateral and in 60% of cases occurs in the inferior or nasal direction.{{citation needed|date=June 2022}}
== Causes ==
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=== Tobacco ===
Smokeless tobacco is implicated as risk factor for
=== Genetic ===
Homocysteine is a non-protein amino acid, synthesized from [[methionine]] and either recycled back into methionine or converted into [[cysteine]] with the aid of the B-group vitamins.
* About 50% of homocysteine {{Citation needed|date=May 2014}} is converted back to methionine by [[remethylation]] via the [[methionine synthase]] major pathway. This requires [[5-methyltetrahydrofolate|active folate]] and vitamin B<sub>12</sub>, in order to donate a methyl group. Active folate is known as 5-methyltetrahydrofolate (5-MTHF).▼
▲* About 50% of homocysteine {{Citation needed|date=May 2014}} is converted back to methionine by remethylation via the [[methionine synthase]] major pathway. This requires [[5-methyltetrahydrofolate|active folate]] and vitamin B<sub>12</sub>, in order to donate a methyl group. Active folate is known as 5-methyltetrahydrofolate (5-MTHF).
* Another pathway for the conversion of homocysteine back to methionine also exists, involving methylation with [[trimethylglycine]] (also called betaine or abbreviated to TMG) as a methyl donor.
* The remaining homocysteine is transsulfurated to cysteine, with vitamin B6 as the co-factor.
Genetic defects in [[MTHFR|5-MTHF reductase]] can consequently lead to hyperhomocysteinemia. The most common [[polymorphism (biology)|polymorphisms]] are known as MTHFR C677T and MTR A2756G.<ref>{{cite journal |doi=10.1186/1475-2891-11-2 |pmid=22230384 |pmc=3274435 |title=MTHFR C677T and MTR A2756G polymorphisms and the homocysteine lowering efficacy of different doses of folic acid in hypertensive Chinese adults |journal=Nutrition Journal |volume=11 |pages=2 |year=2012 |last1=Qin |first1=Xianhui |last2=Li |first2=Jianping |last3=Cui |first3=Yimin |last4=Liu |first4=Zeyuan |last5=Zhao |first5=Zhigang |last6=Ge |first6=Junbo |last7=Guan |first7=Deming |last8=Hu |first8=Jian |last9=Wang |first9=Yanni |last10=Zhang |first10=Fumin |last11=Xu |first11=Xin |last12=Wang |first12=Xiaobin |last13=Xu |first13=Xiping |last14=Huo |first14=Yong |doi-access=free }}</ref><ref>{{cite journal |doi=10.1371/journal.pone.0033222 |pmid=22470444 |pmc=3310006 |title=Polymorphisms in MTHFR, MS and CBS Genes and Homocysteine Levels in a Pakistani Population |journal=PLOS ONE |volume=7 |issue=3 |pages=e33222 |year=2012 |last1=Yakub |first1=Mohsin |last2=Moti |first2=Naushad |last3=Parveen |first3=Siddiqa |last4=Chaudhry |first4=Bushra |last5=Azam |first5=Iqbal |last6=Iqbal |first6=Mohammad Perwaiz |bibcode=2012PLoSO...733222Y |doi-access=free }}</ref>
== Diagnosis ==
A blood test can be performed to quantify total homocysteine concentration in the plasma, of which approximately 80% is generally protein-bound. Classification of hyperhomocysteinemia is defined with respect to serum concentration as follows:{{citation needed|date=June 2022}}
* Moderate: 15–30 nmol/mL (or μmol/L)
* Intermediate: 30–100 nmol/mL
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== Treatment ==
Vitamins B<sub>6</sub>, B<sub>9</sub>, or B<sub>12</sub> supplements (alone or combined)
== See also ==
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{{Medical resources
| DiseasesDB = 29853
| ICD10 =
| ICD9 = {{ICD9|270.4}}
| ICDO =
| OMIM =
| MedlinePlus =
| eMedicineSubj = neuro
| eMedicineTopic = 578
| MeshID =
| SNOMED CT = 419503008
}}
{{Amino acid metabolic pathology}}
{{Authority control}}
[[Category:Amino acid metabolism disorders]]
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