Hereditary atransferrinemia (OMIM #209300) is a rare disorder characterized by severe quantitative or functional deficiency of transferrin. As a consequence, there is reduced delivery of iron to erythroid cells in the marrow, reduced hemoglobin synthesis, increased iron absorption, and severe iron overload of parenchymal organs.

History

In 1961, Heilmeyer and colleagues described atransferrinemia in a girl who had severe hypochromic anemia at age 3 months and severe, progressive generalized iron overload. Patients from other countries with similar abnormalities have been reported subsequently, and explanatory mutations in the gene that encodes transferrin (TF; chromosome 3q21) have been demonstrated in four cases. A similar disorder discovered in inbred mice is due to a splice-site mutation in Tf, the ortholog of TF in humans. Cases of acquired or secondary atransferrinemia or hypotransferrinemia have also been described in patients with diverse underlying conditions.

Clinical description

Manifestations of anemia are the most common clinical abnormalities in patients with hereditary atransferrinemia (Table 19.1). Several probands have had pallor, fatigue, or severe hypochromic, microcytic anemia at birth or in infancy. An Italian infant also had hypovolemia, metabolic acidosis, and persistent fetal circulation. Pallor and anemia were discovered for the first time at age 7 years in a patient from Japan, and at age 20 years in a patient from the US. Most patients have had a systolic ejection murmur attributed to chronic anemia. One patient had mild hepatomegaly.