JMCR: Clinical Minute
Published in Biomedical Research
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A 33-year-old Tanzanian man presented with fatigue, dizziness, cognitive slowing, palmar hyperpigmentation, reduced vibration sensation, and an unsteady Romberg test.
His hemoglobin was 6.5 g/dL. He had pancytopenia, reticulocytopenia, macro-ovalocytes, hypersegmented neutrophils, and an LDH of 8,722 IU/L—classic evidence of severe megaloblastic ineffective hematopoiesis.
Yet his serum vitamin B12 was 356 pg/mL, within the laboratory reference range.
The discordance prompted further evaluation. Intrinsic-factor and parietal-cell antibodies were positive, strongly supporting pernicious anemia. Methylmalonic acid, homocysteine, and holotranscobalamin testing were unavailable.
After vitamin B12 treatment, his hemoglobin rose to 14.8 g/dL by eight weeks, LDH normalized, and the neurological and cutaneous findings improved.
The lesson: do not let one apparently normal serum B12 result overrule a compelling clinical and morphological pattern.
Article Highlights
- Describes advanced clinical and hematological cobalamin deficiency despite serum B12 within the local reference interval.
- Demonstrates macro-ovalocytes, hypersegmented neutrophils, reticulocytopenia, pancytopenia, and marked LDH elevation.
- Identifies intrinsic-factor and parietal-cell antibodies supporting pernicious anemia.
- Illustrates the limitations of total serum B12 immunoassays.
- Emphasizes phenotype-based reasoning where functional biomarkers are unavailable.
- Shows a substantial hematological response after replacement therapy.
Diagnostic caveat
The authors strongly supported pernicious anemia using the clinical phenotype and autoimmune antibodies. Functional biomarkers such as methylmalonic acid, homocysteine, and holotranscobalamin were unavailable, and gastric histology was compatible with—but not diagnostic of—early autoimmune gastritis.
The case should therefore be presented as a well-supported clinicopathological diagnosis rather than proof that every normal serum B12 result represents assay interference.
Clinical Take-Home Message
A serum vitamin B12 concentration within the laboratory reference interval does not exclude clinically important tissue-level deficiency.
When macrocytic anemia, reticulocytopenia, hypersegmented neutrophils, neurological abnormalities, mucocutaneous changes, and ineffective erythropoiesis point toward cobalamin deficiency, investigate further rather than abandoning the diagnosis because of a single total-B12 measurement.
Richard Alan Rison is the Editor-in-Chief of Journal of Medical Case reports. He is also an associate neurology editor (editorial board) for BMC Neurology, and the former lead editor for case reports of BMC Research Notes (currently on the editorial board). His scholarly work focuses on medical case reporting, reporting standards, and editorial methodology. Dr. Rison participated in the development and dissemination of the CARE guidelines for clinical case reporting and has authored numerous publications addressing both neurological disorders and the role of case reports in advancing medical knowledge. Dr. Rison practices general neurology and served as the founding medical director of the PIH Health Hospital-Whittier Stroke Program and the PIH Health Hospital-Whittier Non-Invasive Vascular Laboratory, is a clinical assistant professor of neurology at the University of Southern California Keck School of Medicine and Los Angeles County Medical Center, and is a Fellow of the American Academy of Neurology, the American Neurological Association, and the American Association of Neuromuscular and Electrodiagnostic Medicine. Dr Rison is board-certified by the American Board of Psychiatry and Neurology in neurology and vascular neurology, and neurocritical care and neuroimaging by the United Council of Neurologic Subspecialties. He is also board-certified by the American Board of Electrodiagnostic Medicine in electrodiagnostic medicine. Dr. Rison is a former president of the Los Angeles Neurological Society.
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Journal of Medical Case Reports
This journal will consider any original case report that expands the field of general medical knowledge, and original research relating to case reports.
