Macrocytosis, Familial

Clinical Features

Macrocytosis (large erythrocytes) is commonly associated with anemia and megaloblastosis in vitamin B12 or folate deficiency, cytotoxic drug treatment, and genetic disorders such as orotic aciduria (258900), Imerslund-Grasbeck syndrome (261100), and Lesch-Nyhan syndrome (308000). Nonmegaloblastic macrocytosis can be found in liver disease, alcohol abuse, hypothyroidism, and several hematologic disorders. Fauchald (1970) studied 3 brothers with persistent increase in mean cell volume (MCV) and no demonstrable cause for macrocytosis, indicating the existence of a benign form of familial macrocytosis. Three children of the brothers were investigated without similar findings. Sechi et al. (1994) found more marked macrocytosis with MCV ranging from 110 to 125 fL in a 52-year-old woman. The macrocytosis had been demonstrated since age 40. Her 27-year-old daughter had persistent macrocytosis first demonstrated at the age of 25 although of a lesser degree (from 100 to 110 fL), with normal hemoglobin, mean corpuscular hemoglobin concentration (MCHC), peripheral blood morphology, and blood biochemistries, including liver tests, thyroid hormones, serum vitamin B12, and folate levels.