Paresthesias and Anemia

Posted by Sara Fazio • April 25th, 2012

In the latest Case Record of the Massachusetts General Hospital, a 62-year-old man was admitted to this hospital because of paresthesias, weight loss, jaundice, and anemia. Diagnostic test results were received.

Paresthesias involve a sensation of tingling, numbness, crawling, or deadness, and they are felt mainly in distal parts of the extremities. Although they very rarely involve the thalamus, paresthesias are mostly considered to be related to a spinal cord disorder that probably results from ectopic discharge in damaged dorsal-column axons and may be present before any other abnormalities are detectable on neurologic examination.

Clinical Pearls

Which disorders may be manifested by paresthesias and sensory ataxic gait?

The combination of paresthesias and sensory ataxic gait is typically caused by dysfunction of the dorsal columns, and may be caused by syphilis, tickborne illnesses, human immunodeficiency virus infection, vitamin deficiencies including deficiencies of vitamin B12, folate and vitamin E, and systemic inflammatory conditions such as neoplasia, paraneoplastic syndromes, and autoimmune diseases. Although they are less likely, multiple sclerosis and amyloidosis should also be considered as well.

What is the differential diagnosis of a macrocytic anemia?

The different causes of macrocytic anemia can be classified as arising from immature or stress cells (e.g., reticulocytosis, aplasias, and Fanconi’s anemia), abnormal DNA metabolism (e.g., vitamin B12 and folate deficiency and drugs or toxins), abnormal lipid metabolism (e.g., liver disease and hypothyroidism), a bone marrow disorder (e.g., myelodysplastic syndromes, leukemia, and congenital abnormalities), and an unknown mechanism (e.g., alcoholism and plasma-cell dyscrasias).

Morning Report Questions

Q: What is the classic presentation of vitamin B12 deficiency?

A: The classic triad of clinical findings associated with vitamin B12 deficiency is weakness and fatigue, glossitis, and paresthesias. In addition, other clinical findings include anemia, clumsiness and unsteady gait, nonspecific gastrointestinal symptoms, and weight loss.

Q: What are the laboratory findings associated with pernicious anemia?

A: Classic findings associated with pernicious anemia include atrophic body gastritis and intrinsic factor deficiency. A highly elevated fasting gastrin level (504 pg per milliliter; reference range, <100 pg per milliliter) and a reduced pepsinogen I level (<24.6 ng per milliliter; reference range, 28 to 100 ng per milliliter) are consistent with atrophic body gastritis. The detection of antibodies to intrinsic factor is useful in making the diagnosis of pernicious anemia. In approximately 40 to 60% of patients with pernicious anemia, positivity for anti-intrinsic factor antibodies is present and provides evidence to support the diagnosis, with a specificity approaching 100%.  Homocysteine is elevated in both anemia due to vitamin B12 deficiency and anemia due to folate deficiency. In contrast, the methylmalonic acid level is elevated only in vitamin B12 deficiency and is normal in folate deficiency.

5 Responses to “Paresthesias and Anemia”

  1. Pedro Henrique says:

    The correct paragraph:

    Homocysteine level is elevated in both anemia due to vitamin B12 deficiency and anemia due to folate deficiency.

    In contrast, the Methylmalonic acid level is elevated only in vitamin B12 deficiency and is normal in folate deficiency

  2. Jorge Morales says:

    Kindly review and correct the following statements: ” Methylmalonic acid level is elevated in both anemia due to vitamin B12 deficiency and anemia due to folate deficiency. In contrast, the homocysteine level is elevated only in folate deficiency and is normal in vitamin B12 deficiency.”

    Homocysteine level is elevated both in folate and vitamin B12 deficiency. MMA level is elevated only in anemia due to vitamin B12 deficiency, and is highly specific.

    Thank you

  3. Elissa Leonard says:

    No one wants patients to be injured nor doctors to be sued because of a knowledge gap. Unfortunately this blog entry contains information that is flat out wrong, and it could therefore contribute to the misdiagnosis and delays in treatment that can happen to people with B12 deficiency.

    False:
    “In contrast, the homocysteine level is elevated only in folate deficiency and is normal in vitamin B12 deficiency.”

    B12 deficiency causes an elevation in homocysteine. In the age of folic acid fortification elevations in homocysteine are much more likely to be caused by B12 deficiency than folic acid deficiency. In the age of folic acid fortification, macrocytosis should always be assumed to be caused by B12 deficiency, not folic acid deficiency. Mandatory fortification of flour products in the US with folic-acid-only corrects the macrocytosis doctors may have seen in the past. A persistent knowledge gap means that many practicing physicians risk missing a B12 deficiency in their patients.

    B12 deficiency cannot be ruled out by absence of anemia or macrocytosis. It must be checked for directly. Elevated homocysteine is a red flag, especially in a patient with “low-normal” B12 levels. A normal B12 level does not rule out deficiency, and testing of metabolites methylmalonic acid and homocysteine may be needed.

    Folic-acid-only therapy should never be given to a person with B12 deficiency. It will not correct the nerve damage of a B12 deficiency, and if allowed to progress untreated, a B12 deficiency will lead to permanent damage to nerves and cognition.

    It is legally medically actionable not to rule out B12 deficiency directly in a patient with signs and symptoms. A CBC cannot rule out the deficiency, nor can the absence of anemia, macrocytosis or elevated methylmalonic acid. Treating high homocysteine with folic-acid-only can lead to worsened nerve damage when there is a B12 deficiency.

    Again, no one wants patients to be harmed nor doctors to be sued because of a knowledge gap.

    http://www.cdc.gov/ncbddd/b12/detection.html

    http://www.aafp.org/afp/2003/0301/p979.html

  4. Pedro Henrique says:

    I sent the correction:
    Homocysteine level is elevated in both anemia due to vitamin B12 deficiency and anemia due to folate deficiency.
    In contrast, the Methylmalonic acid level is elevated only in vitamin B12 deficiency and is normal in folate deficiency

  5. Karen Buckley says:

    The last two sentences of the second Morning Report Question should have read “The homocysteine level is elevated in both anemia due to vitamin B12 deficiency and anemia due to folate deficiency. In contrast, the methylmalonic acid level is elevated only in vitamin B12 deficiency and is normal in folate deficiency.” rather than “Methylmalonic acid level is elevated in both anemia due to vitamin B12 deficiency and anemia due to folate deficiency. In contrast, the homocysteine level is elevated only in folate deficiency and is normal in vitamin B12 deficiency.” The information has now been corrected in the post above.

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