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Sections Homocystinuria/Homocysteinemia
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Epidemiology
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Overview

Homocystinuria

Homocystinuria is a disorder of methionine metabolism, leading to an abnormal accumulation of homocysteine and its metabolites (homocystine, homocysteine-cysteine complex, and others) in blood and urine. Normally, these metabolites are not found in appreciable quantities in blood or urine.

Homocystinuria is an autosomal recessively inherited defect in the transsulfuration pathway (homocystinuria I) or methylation pathway (homocystinuria II and III).

Homocysteinemia

Homocysteinemia, a separate but related entity, is defined as elevation of the homocysteine level in blood. This condition has also been referred to as homocyst(e)inemia to reflect metabolites that may accumulate. A mild elevation of plasma homocysteine may exist without homocystinuria.

Homocysteinemia may be due to a genetic predisposition to abnormal activity in the same pathways as homocystinuria. Nutritional and environmental factors, as well as specific medications, may worsen this abnormality and provoke symptoms.

Homocysteine level and stroke

An increased homocysteine level is associated with a higher risk of strokes. Carotid stenosis appears to have a graded response to increased levels of homocysteine. Increased carotid plaque thickness has been associated with high homocysteine and low B12 levels.

A study of both intracranial and extracranial vessels by MR angiography found that homocysteine levels were higher in patients with 2- or 3-vessel stenoses than in those with 1-vessel stenosis.

Yoo JH, Chung CS, Kang SS. Relation of plasma homocyst(e)ine to cerebral infarction and cerebral atherosclerosis. Stroke. 1998 Dec. 29(12):2478-83. [QxMD MEDLINE Link].
Richard E, Desviat LR, Ugarte M, Pérez B. Oxidative stress and apoptosis in homocystinuria patients with genetic remethylation defects. J Cell Biochem. 2013 Jan. 114(1):183-91. [QxMD MEDLINE Link].
Rozen R. Molecular genetic aspects of hyperhomocysteinemia and its relation to folic acid. Clin Invest Med. 1996 Jun. 19(3):171-8. [QxMD MEDLINE Link].
Sellos-Moura M, Glavin F, Lapidus D, Evans K, Lew CR, Irwin DE. Prevalence, characteristics, and costs of diagnosed homocystinuria, elevated homocysteine, and phenylketonuria in the United States: a retrospective claims-based comparison. BMC Health Serv Res. 2020 Mar 6. 20 (1):183. [QxMD MEDLINE Link].
Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, et al. The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet. 1985 Jan. 37(1):1-31. [QxMD MEDLINE Link]. [Full Text].
Kaur M, Kabra M, Das GP, Suri M, Verma IC. Clinical and biochemical studies in homocystinuria. Indian Pediatr. 1995 Oct. 32(10):1067-75. [QxMD MEDLINE Link].
Björksved M, Arnrup K. Homocystinuria and oral health. A report of 14 cases. Swed Dent J. 2012. 36(2):101-8. [QxMD MEDLINE Link].
García-Jiménez MC, Baldellou A, García-Silva MT, Dalmau-Serra J, García-Cazorla A, Gómez-López L, et al. [Epidemiological study of the metabolic diseases with homocystinuria in Spain]. An Pediatr (Barc). 2012 Mar. 76(3):133-9. [QxMD MEDLINE Link].
Majtan T, Kožich V, Kruger WD. Recent therapeutic approaches to cystathionine beta-synthase-deficient homocystinuria. Br J Pharmacol. 2023 Feb. 180 (3):264-278. [QxMD MEDLINE Link].
Cruysberg JR, Boers GH, Trijbels JM, Deutman AF. Delay in diagnosis of homocystinuria: retrospective study of consecutive patients. BMJ. 1996 Oct 26. 313(7064):1037-40. [QxMD MEDLINE Link]. [Full Text].
Morris AA, Kožich V, Santra S, et al. Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis. 2017 Jan. 40 (1):49-74. [QxMD MEDLINE Link].
van den Berg M, van der Knaap MS, Boers GH, Stehouwer CD, Rauwerda JA, Valk J. Hyperhomocysteinaemia; with reference to its neuroradiological aspects. Neuroradiology. 1995 Jul. 37(5):403-11. [QxMD MEDLINE Link].
Schiff M, Blom HJ. Treatment of inherited homocystinurias. Neuropediatrics. 2012 Dec. 43(6):295-304. [QxMD MEDLINE Link].
Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA. 2004 Feb 4. 291(5):565-75. [QxMD MEDLINE Link].
Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009 Apr. 40(4):1365-72. [QxMD MEDLINE Link].

Media Gallery

Homocysteine Metabolism Cycle

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#author-disclosures{display:block}#author-disclosures.modal-layer{position:relative}#author-disclosures .modal-content{max-height:none}#author-disclosures .close-modal{display:none}

Author

Pitchaiah Mandava, MD, PhD Assistant Professor, Department of Neurology, Baylor College of Medicine; Consulting Staff, Department of Neurology, Michael E DeBakey Veterans Affairs Medical Center

Pitchaiah Mandava, MD, PhD is a member of the following medical societies: American Academy of Neurology, Stroke Council of the American Heart Association

Disclosure: Nothing to disclose.

Coauthor(s)

Thomas A Kent, MD Welch Chair in Chemistry Professor, Center for Genomic and Precision Medicine, Institute for Biosciences and Technology, Texas A&M Health Science Center; Adjunct Professor, Stanley H Appel Department of Neurology, Institute for Academic Medicine, Houston Methodist Hospital

Thomas A Kent, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, New York Academy of Sciences, Royal Society of Medicine, Sigma Xi, The Scientific Research Honor Society, Stroke Council of the American Heart Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Howard S Kirshner, MD Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital; Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center

Howard S Kirshner, MD is a member of the following medical societies: Alpha Omega Alpha, American Neurological Association, American Society of Neurorehabilitation, American Academy of Neurology, American Heart Association, American Medical Association, National Stroke Association, Phi Beta Kappa, Tennessee Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke Center

Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology, American Stroke Association

Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2; Physician Advisory Board for Coherex Medical; National Leader and Steering Committee Clinical Trial, Bristol Myers Squibb; Abbott Laboratories, advisory group.

Additional Contributors

Richard M Zweifler, MD Chief of Neurosciences, Sentara Healthcare; Professor and Chair of Neurology, Eastern Virginia Medical School

Richard M Zweifler, MD is a member of the following medical societies: American Academy of Neurology, American Stroke Association, Stroke Council of the American Heart Association, American Heart Association, American Medical Association

Disclosure: Nothing to disclose.

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Sections Homocystinuria/Homocysteinemia
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