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.
• 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.