Pernicious Anemia: Basic Pathophysiology and Diagnostic Challenges in Neuropsychiatric Patients

Pernicious anemia (PA) represents a significant diagnostic challenge in neuropsychiatric patients due to its subtle and variable presentation. While PA is traditionally associated with clinical and biochemical manifestations of anemia, many patients, particularly those with neuropsychiatric symptoms, may have normal hematologic parameters, delaying recognition and appropriate treatment. Neurological and psychiatric symptoms, ranging from cognitive impairment and mood disorders to subacute combined degeneration (SCD) of the spinal cord, can precede hematologic abnormalities, leading to misdiagnosis or inappropriate management. The lack of a definitive gold standard test for cobalamin deficiency (CD) further complicates identification. Commonly used biomarkers, such as serum cobalamin, methylmalonic acid (MMA), homocysteine (Hcy), intrinsic factor antibodies (IFAs), and parietal cell antibodies (PCAs), each have limitations in diagnosing PA, especially in the absence of overt anemia. The variability in diagnostic criteria and cutoff values across studies adds to the challenge of achieving early and accurate diagnosis. This article reviews the complexities of diagnosing PA in neuropsychiatric patients, evaluates the limitations of current diagnostic methods, and emphasizes the need for a more comprehensive, standardized approach to early detection and treatment. Combining clinical awareness with improved biomarker interpretation is essential for preventing irreversible neurological damage and improving patient outcomes. Improved diagnostic protocols and further research are essential to optimize detection and minimize the risk of long-term neurological damage.