Megaloblastic Anemia: Cobalamin and Folate Deficiency
The symptoms of megaloblastic anemia parallel those of anemia in general: weakness, fatigue, dyspnea, and light-headedness. Pallor and jaundice combine to produce the classic lemon-yellow skin of megaloblastic anemia. Additionally, patients may develop a beefy, red smooth tongue, weight loss, thrombocytopenia, and neutropenia. Classically, the neutrophils have hyper-segmented nuclei (>5 lobes).
Cobalamin (Vitamin B12) Deficiency
Cobalamin deficiency can produce a neurologic syndrome that may precede the development of megaloblastic anemia. Importantly, the neurological manifestations require immediate treatment to prevent irreversible deficits. The initial symptoms are usually characterized by paresthesias of the fingers and feet along with a decrease in proprioception and vibratory sense. If left untreated, the syndrome can progress to spastic ataxia. The syndrome is caused by demyelination of the dorsal and lateral columns of the spinal cord. Dementia mimicking Alzheimer disease may also develop. Megaloblastic madness describes patients with cobalamin deficiencies that develop psychosis.
Serum B12 levels are almost always low. In borderline cases, serum methylmalonic acid and homocysteine levels can be measured; both are elevated in B12 deficiency. Once the diagnosis is established, the underlying cause must be determined. Antiintrinsic factor and antiparietal cell antibodies should be quantitated to establish the diagnosis of pernicious anemia. Upper endoscopy may reveal an intestinal cause (malabsorption). The three-part Shilling test is largely of historical significance and is rarely used today.
Treatment consists of vitamin B12 1000 ug intramuscularly daily for 7 days, then weekly for 1 month, then monthly for life unless the underlying etiology is correctable. B12 administration produces a reticulocytosis within 5 to 7 days, followed by resolution of hematologic abnormalities in 2 to 3 months. The neurologic symptoms may not resolve, particularly if they have been present for a significant period of time.
Unlike cobalamin, there are no neurological abnormalities associated with folate deficiency. However, administration of folate to a cobalamin-deficient patient can correct the anemia but will have no effect on the neurologic features. Therefore, it is imperative to distinguish B12 deficiency from folate deficiency.
Both serum and RBC folate levels should be measured. The serum folate reflects recent folate intake (preceding few days) and, therefore can be falsely normal after a single folate-rich meal. The RBC folate levels, which reflect folate turnover during the preceding 2 to 3 months, are a better indicator of tissue stores.
Folate deficiency is treated with oral folate 1 mg/day. To prevent a relapse, treatment should be continued for at least 2 years.