Biochemical and genetic defects underlying human congenital hypotransferrinemia

Introduction: Human congenital hypotransferrinemia is a rare disorder characterized by the virtual absence of transferrin in the serum. No information on the causes of the disease is known. Materials and methods: Here we describe the identification of a new case, its treatment and the biochemical and genetic defects underlying the disorder. Results: At diagnosis the patient had serum Tf levels equal to about 1% of the normal values. The treatment with plasma infusions each month allowed a good erythropoiesis and the prevention of iron overload with no need of red blood cell transfusions or iron chelators. In order to define the genetic basis of the disease, we performed a haplotype analysis of the Tf gene region in the 26 individuals forming the proband's family, and demonstrated that the genetic defect is located in the Tf gene and that it is inherited as a recessive trait. Protein analyses indicate that the proband serum contains two transferrin forms: one of 80 kD analogous to the n...