PROSPECTIVE OVERVIEW - NEUROPSYCHIATRIC DISORDERS CAUSED BY COBALAMINDEFICIENCY IN THE ABSENCE OF ANEMIA OR MACROCYTOSIS

Among 141 consecutive patients with neuropsychiatric abnormalities due to cobalamin deficiency, we found that 40 (28 percent) had no anemia or macrocytosis. The hematocrit was normal in 34, the mean cell volume was normal in 25, and both tests were normal in 19, Characteristic fe atures in such patients included paresthesia, sensory loss, ataxia, de mentia, and psychiatric disorders; longstanding neurologic symptoms wi thout anemia; normal white-cell and platelet counts and serum bilirubi n and lactate dehydrogenase levels; and markedly elevated serum concen trations of methylmalonic acid and total homocysteine, Serum cobalamin levels were above 150 pmol per lifer (200 pg per milliliter) in 2 pat ients, between 75 and 150 pmol per liter (100 and 200 pg per millilite r) in 16, and below 75 pmol per liter (100 pg per milliliter) in only 22. Except for one patient who died during the first week of treatment , every patient in this group benefited from cobalamin therapy. Respon ses included improvement in neuropsychiatric abnormalities (39 of 39), improvement (often within the normal range) in one or more hematologi c findings (36 of 39), and a decrease of more than 50 percent in level s of serum methylmalonic acid, total homocysteine, or both (31 of 31). We conclude that neuropsychiatric disorders due to cobalamin deficien cy occur commonly in the absence of anemia or an elevated mean cell vo lume and that measurements of serum methylmalonic acid and total homoc ysteine both before and after treatment are useful in the diagnosis of these patients.