Current concepts in the diagnosis of cobalamin deficiency

Abstract

Intellectual satisfaction derived from making a correct diagnosis is heightened by the knowledge that treatment, free of side effects, can prevent further progression of disease and may even reverse some or all of the disease manifestations. The paradigm for this situation in neurology has been the disease pernicious anemia (PA), with its associated deficiency of cobalamin (Cbl) leading, if untreated, to progressive spinal cord degeneration, neuropathy, and cerebral complications. There was a time when an astute clinician might have considered that the diagnosis of PA or other causes of Cbl deficiency was relatively simple and treatment straightfor-ward. A patient experiencing neurologic complaints, often affecting sensory and motor function in the lower extremities, would have been found to have macrocytic anemia. To confirm the suspicion, the patient might have had a smooth tongue, prematurely graying hair, lemon-yellow skin, and a family history of anemia requiring monthly ``vitamin shots.'' The diagnosis would have been confirmed by a serum Cbl determination followed by treatment with vitamin cyanocobalamin (vitamin B12; B12). Despite, or perhaps because of, a number of advances in our understanding of Cbl metabolism, we more frequently encounter patients with unusual or atypical clinical and laboratory features who have underlying Cbl deficiency. Subacute combined degeneration of the spinal cord, neuropathy, and other classic manifestations of Cbl deficiency in the nervous system are often easy to recognize, but we now know that there are many atypical presentations. [1-4] Some patients have neurologic syndromes without anemia or macrocytosis, whereas others have a normal serum Cbl level, yet are found to have other biochemical evidence of Cbl deficiency such as raised levels of the metabolites methylmalonic acid and homocysteine. Appropriate investigation is critical, because early treatment affords the possibility of excellent recovery. What are the reasons for this seeming change from …