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Metabolic Disease and Stroke - Homocystinuria/Homocysteinemia: Differential Diagnoses & Workup

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
Coauthor(s): Thomas A Kent, MD, Professor, Department of Neurology, Baylor College of Medicine; Neurology Care Line Executive, Michael E DeBakey Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: May 25, 2009

Differential Diagnoses

Blood Dyscrasias and Stroke
Metabolic Disease & Stroke: Fabry Disease
Metabolic Disease & Stroke: Methylmalonic Acidemia
Metabolic Disease & Stroke: Propionic Acidemia

Other Problems to Be Considered

Carotid disease and stroke

Workup

Laboratory Studies

  • Homocystinuria: If patients present with systemic signs and symptoms, screening tests followed by confirmatory tests may be done.
    • The urine screening test for sulfur-containing amino acids, called the cyanide nitroprusside test, can be undertaken; however, high rates of false-negative as well as false-positive results are reported.
    • A neonatal screening test, called the Guthrie test, detects high levels of methionine in heel-stick blood. This test is performed routinely in several states for detection of phenylalanine, leucine, and methionine. Because of high false-negative results in homocystinuric patients, a recent report suggested lowering the threshold of methionine to qualify as abnormal.
    • Quantitative tests for homocystine in urine and blood are available commercially. The blood specimen needs to be handled in a specific manner described in the homocysteinemia testing section.
    • Measurement of CBS activity in cultured fibroblasts provides definitive support for the diagnosis.
    • Testing of amniotic cells and chorionic villi is also available.
  • Homocysteinemia: Lab studies may be considered in patients who present with symptoms of acute stroke in the absence of traditional risk factors such as hypertension, smoking, and diabetes. Nutritional factors, environmental toxins, or medical conditions may worsen an inherent homocysteinemia. Some caveats follow:
    • No consensus exists on the timing of the test with respect to an acute event.
    • Whether a methionine challenge should be used for testing is not clear at this juncture. The methionine challenge test may be more appropriate if a deficiency is suspected in the transsulfuration pathway.
    • Specimens for total and free homocystine measurement must be handled and processed in a specific way: they must be put on ice and spun within 1 hour. Whether the specifications are always followed by all laboratories or medical offices is unclear.
    • The risk for vascular disease is graded with respect to the level of homocysteine; however, no threshold abnormal value is accepted widely.
    • If homocysteinemia is determined by a test, then tests for deficiency in folic acid, vitamin B-12, and pyridoxine also may be performed.
    • Genetic abnormalities are reported on chromosome 1 pertaining to MTHFR; however, the mere presence of this abnormality may not confer a risk for vascular disease.

Imaging Studies

  • On routine imaging studies, bony abnormalities including osteoporosis may be readily apparent.
  • A CT scan of the head is obtained routinely in patients presenting with acute stroke. Where available, MRI with newer techniques such as diffusion and perfusion imaging and MR angiography also may be used in the acute setting.
  • MRI5 and CT findings with either homocystinuria or classic homocysteinemia may show both large-vessel or lacunar strokes, potentially in any vascular distribution.

Other Tests

Acute stroke diagnosis and treatment requires that certain laboratory studies such as complete blood count, chemistries, prothrombin/activated partial thromboplastin times (PT/aPTT), brain imaging, echocardiography, and vascular studies be done to exclude the usual causes, some of which may be treatable or preventable.

More on Metabolic Disease and Stroke - Homocystinuria/Homocysteinemia

Overview: Metabolic Disease and Stroke - Homocystinuria/Homocysteinemia
Differential Diagnoses & Workup: Metabolic Disease and Stroke - Homocystinuria/Homocysteinemia
Treatment & Medication: Metabolic Disease and Stroke - Homocystinuria/Homocysteinemia
Follow-up: Metabolic Disease and Stroke - Homocystinuria/Homocysteinemia
References
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References

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Further Reading

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Keywords

homocysteinuria, homocystinemia, metabolic disease, stroke, disorder of methionine metabolism, stroke treatment, stroke symptoms, abnormal accumulation of homocysteine in blood and urine

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Contributor Information and Disclosures

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, Sigma Xi, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Coauthor(s)

Thomas A Kent, MD, Professor, Department of Neurology, Baylor College of Medicine; Neurology Care Line Executive, Michael E DeBakey Veterans Affairs Medical Center
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, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Medical Editor

Richard M Zweifler, MD, Chief of Neurology, Sentara Healthcare, Norfolk, VA; Professor of Neurology, Eastern Virginia Medical School, Norfolk, VA
Richard M Zweifler, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Medical Association, American Stroke Association, Royal Society of Medicine, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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 Academy of Neurology, American Heart Association, American Medical Association, American Neurological Association, American Society of Neurorehabilitation, National Stroke Association, Phi Beta Kappa, and Tennessee Medical Association
Disclosure: Boehringer Ingelheim Honoraria Speaking and teaching; BMS/Sanofi Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD, Professor, Department of Neurology, Oregon Health & Science University; Associate Director, Oregon Stroke Center
Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology and American Stroke Association
Disclosure: Co-Axia Consulting fee Review panel membership; Talecris Consulting fee Review panel membership; AGA Medical Consulting fee Review panel membership; Boehringer Ingelheim Honoraria Speaking and teaching; Concentric Medical Consulting fee Review panel membership; Abbott Consulting fee Consulting; Sanofi  Consulting

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