Pernicious Anemia Differential Diagnoses

Updated: May 16, 2022
  • Author: Srikanth Nagalla, MD, MS, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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Diagnostic Considerations

By definition, pernicious anemia refers specifically to vitamin B12 deficiency resulting from a lack of production of intrinsic factor (IF) in the stomach. However, vitamin B12 absorption is a complex process, and other causes of vitamin B12 deficiency exist. Pernicious anemia must be differentiated from other disorders that interfere with the absorption and metabolism of vitamin B12 and produce cobalamin deficiency, with the development of a macrocytic anemia and neurologic complications.

Go to Anemia, Iron Deficiency Anemia, and Chronic Anemia for complete information on these topics.

Thiamine-responsive megaloblastic anemia syndrome (TRMA) is an autosomal recessive disorder characterized by megaloblastic anemia, progressive sensorineural hearing loss, and diabetes mellitus. Onset of megaloblastic anemia occurs between infancy and adolescence. Vitamin B12 and folic acid levels are normal. On bone marrow examination, affected individuals have megaloblastic changes with erythroblasts often containing iron-filled mitochondria (ringed sideroblasts). Molecular genetic testing will show biallelic pathogenic variants in SLC19A2. [18]  

Uncommonly, variable ocular anomalies may be present in TRMA. One case report describes symmetric bull's eye maculopathy and other ocular findings consistent with cone-rod degeneration. [19]

The anemia in TRMA is corrected with pharmacologic doses (50-100 mg/day) of thiamine (vitamin B1) . However, the red cells remain macrocytic. [18]

Other conditions to be considered include the following:

  • Cestode infection
  • Neurologic disorders
  • Senility

Pernicious anemia may rarely be associated with liver disease (eg, primary biliary cholangitis, autoimmune hepatitis, interferon-treated hepatitis C). Yan et al report two cases of pernicious anemia in patients with cryptogenic cirrhosis, in both of whom the neuropsychiatric symptoms of pernicious anemia were initially attributed to hepatic encephalopathy. [20]

Differential Diagnoses