Diferencia entre revisiones de «Homocistinuria»
J3D3 trasladó la página Homocistinuria a Hiperhomocisteinemia: El contenido del artículo se corresponde con esa enfermedad. No con la homocistinuria. |
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{{Infobox disease |
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| Name = Homocistinuria |
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| Image = L-Homocysteine.svg |
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| Caption = [[Homocisteína]] |
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| DiseasesDB = 5991 |
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| ICD10 = {{ICD10|E|72|1|e|70}} |
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| ICD9 = {{ICD9|270.4}} |
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| ICDO = |
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| OMIM = 236200 |
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| MedlinePlus = 001199 |
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| eMedicineSubj = derm |
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| eMedicineTopic = 708 |
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| MeshID = D006712 |
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| GeneReviewsNBK = NBK1524 |
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| GeneReviewsName = Homocistinuria causada por deficiencia de cistationina beta sintasa |
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}} |
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La '''homocistinuria''' clásica, conocida también como '''deficiencia de cistationina beta sintasa''' o '''deficiencia de CBS''',<ref name=omim/> es una enfermedad hereditaria del [[metabolismo]] del [[aminoácido]] [[metionina]], que a menudo involucra un defecto en la enzima [[cistationina beta sintasa]]. Es una enfermedad hereditaria que se expresa con un patrón de herencia [[autosómico recesivo]], lo que significa que un niño debe heredar una copia defectuosa del gen que codifica para esta enzima de ambos padres para manifestar la enfermedad. |
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== Signos y síntomas == |
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Este defecto conduce a un trastorno multisistémico del [[tejido conectivo]], [[músculo]]s, [[sistema nervioso central]] (SNC), y [[sistema cardiovascular]]. La homocistinuria representa a un grupo de [[desorden metabólico|desórdenes metabólicos]] caracterizado por la acumulación del aminoácido [[homocisteína]] en el plasma sanguíneo, y un aumento en la excreción de homocisteína en la [[orina]]. Los niños aparentan ser normales, y cualquier síntoma temprano, si se hace presente, suele ser inespecífico y vago. |
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Signs and symptoms of homocystinuria that may be seen include the following: |
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* A family history of homocystinuria<ref name="pmid18423051">{{cite journal |author=Maillot F, Kraus JP, Lee PJ |title=Environmental influences on familial discordance of phenotype in people with homocystinuria: a case report |journal=J Med Case Reports |volume=2 |issue= 1|pages=113 |year=2008 |pmid=18423051 |pmc=2377250 |doi=10.1186/1752-1947-2-113 |url=http://www.jmedicalcasereports.com/content/2//113}}</ref> |
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* [[Flushing (physiology)|Flush]] across the cheeks |
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* Musculoskeletal |
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** Tall, thin build resembling [[Marfanoid|Marfanoid habitus]]<ref name=omim/> |
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** Long limbs ([[dolichostenomelia]]) |
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** High-arched feet ([[pes cavus]]) |
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** Knock knees ([[genu valgum]]) |
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** [[Pectus excavatum]] and [[Pectus carinatum]] |
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* [[Intellectual disability]] |
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* [[Seizures]] |
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* [[Psychiatric disease]] |
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* Eye anomalies: |
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** [[Ectopia lentis]] – in contrast to [[Marfan syndrome]] which features upward ectopia lentis, downward dislocation is the typical finding of homocystinuria<ref name="RobinsonGodfrey2004">{{cite book|author1=Peter Nicholas Robinson|author2=Maurice Godfrey|title=Marfan syndrome: a primer for clinicians and scientists|url=http://books.google.com/?id=eX4B9WASDpAC&pg=PA5|accessdate=12 April 2010|year=2004|publisher=Springer|isbn=978-0-306-48238-0|pages=5–}}</ref> or [[subluxation]] of [[lens (anatomy)|lens]] |
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** [[Myopia]] ([[nearsightedness]]) |
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** [[Glaucoma]] |
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** [[Optic atrophy]] |
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** [[Retinal detachment]]<ref name=Cecil>{{cite book|last=Goldman|first=Lee|title=Goldman's Cecil Medicine|publisher=Elsevier Saunders|location=Philadelphia|isbn=1437727883|year=2011|pages=1362|edition=24th}}</ref> |
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** [[Cataract]]s |
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* [[Vascular disease]] |
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** Extensive [[atheroma]] formation at a young age which affects many arteries but not the coronary arteries |
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** Intravascular [[thrombosis]] |
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== Diagnóstico de laboratorio == |
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The term homocystinuria describes an increased excretion of the [[thiol]] [[amino acid]] [[homocysteine]] in urine (and incidentally, also an increased concentration in [[blood plasma|plasma]]). The source of this increase may be one of many metabolic factors, only one of which is CBS deficiency. Others include the re-methylation defects ([[cobalamin]] defects, [[methionine]] sythase deficiency, [[MTHFR]]) and vitamin deficiencies (cobalamin (vitamin B12) deficiency, [[folate]] (vitamin B9) deficiency, [[riboflavin]] deficiency (vitamin B2), [[pyridoxal phosphate]] deficiency (vitamin B6)). In light of this information, a combined approach to laboratory diagnosis is required to reach a differential diagnosis. |
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CBS deficiency may be diagnosed by routine metabolic biochemistry. In the first instance, plasma or urine amino acid analysis will frequently show an elevation of methionine and the presence of homocysteine. Many neonatal screening programs include methionine as a metabolite. The disorder may be distinguished from the re-methylation defects (e.g., MTHFR, methionine synthase deficiency and the cobalamin defects) in lieu of the elevated methionine concentration.<ref>{{cite book|last=(eds.)|first=N. Blau ...|title=Physician's guide to the laboratory diagnosis of metabolic diseases ; with 270 tables|year=2003|publisher=Springer|location=Berlin [u.a.]|isbn=354042542X|edition=2.}}</ref> Additionally, organic acid analysis or quantitative determination of methylmalonic acid should help to exclude cobalamin (vitamin B12) defects and vitamin B12 deficiency giving a differential diagnosis.<ref>{{cite journal|last=Refsum|first=Helga|coauthors=A. David Smith, Per M. Ueland, Ebba Nexo, Robert Clarke, Joseph McPartlin, Carole Johnston, Frode Engbaek, Jørn Schneede, Catherine McPartlin, and John M. Scott|title=Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion|journal=Clinical Chemistry|year=2004|volume=50|issue=1|pages=3–32|pmid=14709635|doi=10.1373/clinchem.2003.021634}}</ref> |
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The laboratory analysis of homocysteine itself is complicated because most homocysteine (possibly above 85%) is bound to other thiol amino acids and proteins in the form of [[disulphides]] (e.g., [[cysteine]] in cystine-homocysetine, [[homocysteine]] in homocysteine-homocysteine) via [[disulfide bonds]]. Since as an equilibrium process the proportion of free homocystene is variable a true value of total homocysteine (free + bound) is useful for confirming diagnosis and particularly for monitoring of treatment efficacy. To this end it is prudent to perform total homocyst(e)ine analysis in which all disulphide bonds are subject to [[redox|reduction]] prior to analysis, traditionally by [[HPLC]] after [[derivatisation]] with a fluorescent agent, thus giving a true reflection of the quantity of homocysteine in a plasma sample.<ref>{{cite journal|last=Carducci|first=Claudia|author2=M. Birarelli |author3=M. Nola |author4=I. Antonozzi |title=Automated high-performance liquid chromatographic method for the determination of homocysteine in plasma samples|journal=Journal of Chromatography A|year=1999|volume=846|pages=93–100|pmid=10420601|doi=10.1016/S0021-9673(98)01091-7|issue=1–2}}</ref> |
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== Tratamiento == |
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No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B<sub>6</sub> (also known as [[pyridoxine]]).<ref name=vit>{{Cite journal| pmid = 9259028 | last1 = Bakker | date = June 1997 | first1 = R. C. | last2 = Brandjes | first2 = D. P. | title = Hyperhomocysteinaemia and associated disease | volume = 19 | issue = 3| pages = 126–132| journal = Pharmacy world & science : PWS| doi = 10.1023/A:1008634632501}}</ref> Slightly less than 50% respond to this treatment and need to take supplemental vitamin B<sub>6</sub> for the rest of their lives. Those who do not respond require a [[Low-sulfur diet]] (especially monitoring [[methionine]]), and most will need treatment with [[trimethylglycine]]. A normal dose of [[folic acid]] supplement and occasionally adding [[cysteine]] to the diet can be helpful, as [[glutathione]] is synthesized from cysteine (so adding cysteine can be important to reduce [[oxidative stress]]). |
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Betaine (N,N,N-trimethylglycine) is used to reduce concentrations of homocysteine by promoting the conversion of homocysteine back to methionine, i.e., increasing flux through the re-methylation pathway independent of folate derivatives (which is mainly active in the liver and in the kidneys).The re-formed methionine is then gradually removed by incorporation into body protein. The methionine that is not converted into protein is converted to S-adenosyl-methionine which goes on to form homocysteine again. Betaine is, therefore, only effective if the quantity of methionine to be removed is small. Hence treatment includes both betaine and a diet low in methionine. In classical homocystinuria (CBS, or cystathione beta synthase deficiency), the plasma methionine level usually increases above the normal range of 30 micromoles/L and the concentrations should be monitored as potentially toxic levels (more than 400 micromoles/L) may be reached. |
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=== Dieta recomendada === |
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Para esta enfermedad se recomienda una dieta baja en proteínas, la cual requiere de productos alimenticios con bajo contenido en algunos tipos de aminoácidos, tales como por ejemplo de [[metionina]].{{Citation needed|date=August 2015}} |
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== Pronóstico == |
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La expectativa de vida de los pacientes con homocistinuria es menor a la media si la enfermedad no se trata. Se sabe que antes de los 30 años casi un cuarto de los pacientes sin tratamiento fallecen a causa de complicaciones trombóticas, tales como por ejemplo el [[infarto de miocardio]].{{Citation needed|date=August 2015}} |
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== En la historia y la cultura == |
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Una teoría sugiere que [[Akenatón]], un faraón de la dieciochoava dinastía de Egipto, podría haber sufrido de homocistinuria.<ref name=" pmid = 20402329 "/> |
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== Véase también == |
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* [[Cistinuria]] |
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| ⚫ | |||
== Referencias == |
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{{listaref|2|refs="<ref name=omim>{{OMIM|236200}}</ref> |
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<ref name=" pmid = 20402329 ">{{cite journal | author = Cavka M, Kelava T | title = Homocystinuria, a possible solution of the Akhenaten's mystery | journal = Coll Antropol. | volume = 34 | issue = |date=Mar 2010 | pmid = 20402329 | url = http://hrcak.srce.hr/file/79191 | pages = 255–58}}</ref>"}} |
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== Enlaces externos == |
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* [http://www.hcusupport.com/diet.htm Homocystinuria Support] |
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* [http://www.ncbi.nlm.nih.gov/books/NBK1524/ GeneReview/NIH/UW entry on Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency] |
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* [http://docs.google.com/viewer?a=v&pid=sites&srcid=ZGVmYXVsdGRvbWFpbnxtdWx0aWZhY3RvcmhlYWx0aHxneDoyMjRkY2I4NmI2MDZlNTc4 Paper and discussion on Homocystinuria due to Cystathionine Beta Synthase deficiency] |
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[[Categoría:Enfermedades autonsómicas recesivas]] |
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[[Categoría:Enfermedades del metabolismo de los amioácidos]] |
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Revisión del 17:27 24 mar 2016
| Homocistinuria | ||
|---|---|---|
| Especialidad |
endocrinología genética médica | |
| eMedicine | derm/708 | |
La homocistinuria clásica, conocida también como deficiencia de cistationina beta sintasa o deficiencia de CBS,[1] es una enfermedad hereditaria del metabolismo del aminoácido metionina, que a menudo involucra un defecto en la enzima cistationina beta sintasa. Es una enfermedad hereditaria que se expresa con un patrón de herencia autosómico recesivo, lo que significa que un niño debe heredar una copia defectuosa del gen que codifica para esta enzima de ambos padres para manifestar la enfermedad.
Signos y síntomas
Este defecto conduce a un trastorno multisistémico del tejido conectivo, músculos, sistema nervioso central (SNC), y sistema cardiovascular. La homocistinuria representa a un grupo de desórdenes metabólicos caracterizado por la acumulación del aminoácido homocisteína en el plasma sanguíneo, y un aumento en la excreción de homocisteína en la orina. Los niños aparentan ser normales, y cualquier síntoma temprano, si se hace presente, suele ser inespecífico y vago.
Signs and symptoms of homocystinuria that may be seen include the following:
- A family history of homocystinuria[2]
- Flush across the cheeks
- Musculoskeletal
- Tall, thin build resembling Marfanoid habitus[1]
- Long limbs (dolichostenomelia)
- High-arched feet (pes cavus)
- Knock knees (genu valgum)
- Pectus excavatum and Pectus carinatum
- Intellectual disability
- Seizures
- Psychiatric disease
- Eye anomalies:
- Ectopia lentis – in contrast to Marfan syndrome which features upward ectopia lentis, downward dislocation is the typical finding of homocystinuria[3] or subluxation of lens
- Myopia (nearsightedness)
- Glaucoma
- Optic atrophy
- Retinal detachment[4]
- Cataracts
- Vascular disease
- Extensive atheroma formation at a young age which affects many arteries but not the coronary arteries
- Intravascular thrombosis
Diagnóstico de laboratorio
The term homocystinuria describes an increased excretion of the thiol amino acid homocysteine in urine (and incidentally, also an increased concentration in plasma). The source of this increase may be one of many metabolic factors, only one of which is CBS deficiency. Others include the re-methylation defects (cobalamin defects, methionine sythase deficiency, MTHFR) and vitamin deficiencies (cobalamin (vitamin B12) deficiency, folate (vitamin B9) deficiency, riboflavin deficiency (vitamin B2), pyridoxal phosphate deficiency (vitamin B6)). In light of this information, a combined approach to laboratory diagnosis is required to reach a differential diagnosis.
CBS deficiency may be diagnosed by routine metabolic biochemistry. In the first instance, plasma or urine amino acid analysis will frequently show an elevation of methionine and the presence of homocysteine. Many neonatal screening programs include methionine as a metabolite. The disorder may be distinguished from the re-methylation defects (e.g., MTHFR, methionine synthase deficiency and the cobalamin defects) in lieu of the elevated methionine concentration.[5] Additionally, organic acid analysis or quantitative determination of methylmalonic acid should help to exclude cobalamin (vitamin B12) defects and vitamin B12 deficiency giving a differential diagnosis.[6]
The laboratory analysis of homocysteine itself is complicated because most homocysteine (possibly above 85%) is bound to other thiol amino acids and proteins in the form of disulphides (e.g., cysteine in cystine-homocysetine, homocysteine in homocysteine-homocysteine) via disulfide bonds. Since as an equilibrium process the proportion of free homocystene is variable a true value of total homocysteine (free + bound) is useful for confirming diagnosis and particularly for monitoring of treatment efficacy. To this end it is prudent to perform total homocyst(e)ine analysis in which all disulphide bonds are subject to reduction prior to analysis, traditionally by HPLC after derivatisation with a fluorescent agent, thus giving a true reflection of the quantity of homocysteine in a plasma sample.[7]
Tratamiento
No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B6 (also known as pyridoxine).[8] Slightly less than 50% respond to this treatment and need to take supplemental vitamin B6 for the rest of their lives. Those who do not respond require a Low-sulfur diet (especially monitoring methionine), and most will need treatment with trimethylglycine. A normal dose of folic acid supplement and occasionally adding cysteine to the diet can be helpful, as glutathione is synthesized from cysteine (so adding cysteine can be important to reduce oxidative stress).
Betaine (N,N,N-trimethylglycine) is used to reduce concentrations of homocysteine by promoting the conversion of homocysteine back to methionine, i.e., increasing flux through the re-methylation pathway independent of folate derivatives (which is mainly active in the liver and in the kidneys).The re-formed methionine is then gradually removed by incorporation into body protein. The methionine that is not converted into protein is converted to S-adenosyl-methionine which goes on to form homocysteine again. Betaine is, therefore, only effective if the quantity of methionine to be removed is small. Hence treatment includes both betaine and a diet low in methionine. In classical homocystinuria (CBS, or cystathione beta synthase deficiency), the plasma methionine level usually increases above the normal range of 30 micromoles/L and the concentrations should be monitored as potentially toxic levels (more than 400 micromoles/L) may be reached.
Dieta recomendada
Para esta enfermedad se recomienda una dieta baja en proteínas, la cual requiere de productos alimenticios con bajo contenido en algunos tipos de aminoácidos, tales como por ejemplo de metionina.[cita requerida]
Pronóstico
La expectativa de vida de los pacientes con homocistinuria es menor a la media si la enfermedad no se trata. Se sabe que antes de los 30 años casi un cuarto de los pacientes sin tratamiento fallecen a causa de complicaciones trombóticas, tales como por ejemplo el infarto de miocardio.[cita requerida]
En la historia y la cultura
Una teoría sugiere que Akenatón, un faraón de la dieciochoava dinastía de Egipto, podría haber sufrido de homocistinuria.[9]
Véase también
Referencias
- ↑ a b OMIM 236200
- ↑ Maillot F, Kraus JP, Lee PJ (2008). «Environmental influences on familial discordance of phenotype in people with homocystinuria: a case report». J Med Case Reports 2 (1): 113. PMC 2377250. PMID 18423051. doi:10.1186/1752-1947-2-113.
- ↑ Peter Nicholas Robinson; Maurice Godfrey (2004). Marfan syndrome: a primer for clinicians and scientists. Springer. pp. 5-. ISBN 978-0-306-48238-0. Consultado el 12 April 2010.
- ↑ Goldman, Lee (2011). Goldman's Cecil Medicine (24th edición). Philadelphia: Elsevier Saunders. p. 1362. ISBN 1437727883.
- ↑ (eds.), N. Blau ... (2003). Physician's guide to the laboratory diagnosis of metabolic diseases ; with 270 tables (2. edición). Berlin [u.a.]: Springer. ISBN 354042542X.
- ↑ Refsum, Helga; A. David Smith, Per M. Ueland, Ebba Nexo, Robert Clarke, Joseph McPartlin, Carole Johnston, Frode Engbaek, Jørn Schneede, Catherine McPartlin, and John M. Scott (2004). «Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion». Clinical Chemistry 50 (1): 3-32. PMID 14709635. doi:10.1373/clinchem.2003.021634.
- ↑ Carducci, Claudia; M. Birarelli; M. Nola; I. Antonozzi (1999). «Automated high-performance liquid chromatographic method for the determination of homocysteine in plasma samples». Journal of Chromatography A 846 (1–2): 93-100. PMID 10420601. doi:10.1016/S0021-9673(98)01091-7.
- ↑ Bakker, R. C.; Brandjes, D. P. (June 1997). «Hyperhomocysteinaemia and associated disease». Pharmacy world & science : PWS 19 (3): 126-132. PMID 9259028. doi:10.1023/A:1008634632501.
- ↑ Cavka M, Kelava T (Mar 2010). «Homocystinuria, a possible solution of the Akhenaten's mystery». Coll Antropol. 34: 255-58. PMID 20402329.