title: Biochemical and genetic defects underlying human congenital hypotransferrinemia.
abstract: BACKGROUND
  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.
  
  
  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 normal one, and a smaller one of 50 kD, which may arise from a specific degradation or be the gene product of a modified allele.
  
  
  CONCLUSIONS
  These data suggest the presence of two Tf alleles carrying genetic defects that cause two distinct abnormalities. One allele causes low expression of an apparently normal protein that probably allowed the survival of the patient in the first years of age. The other allele produces a modified Tf with different biochemical characteristics compared to the normal one.
authors.affiliation: Pediatric Clinic, Fondazione M. Tettamanti, University of Milano-Bicocca, Ospedale Nuovo San Gerardo, via Donizetti 106, 20052 Monza (MI), Italy. fondazione.tettamanti@galactica.it
authors.forename: S
authors.initials: S
authors.lastname: Goldwurm
authors.forename: C
authors.initials: C
authors.lastname: Casati
authors.forename: N
authors.initials: N
authors.lastname: Venturi
authors.forename: S
authors.initials: S
authors.lastname: Strada
authors.forename: P
authors.initials: P
authors.lastname: Santambrogio
authors.forename: S
authors.initials: S
authors.lastname: Indraccolo
authors.forename: P
authors.initials: P
authors.lastname: Arosio
authors.forename: M
authors.initials: M
authors.lastname: Cazzola
authors.forename: A
authors.initials: A
authors.lastname: Piperno
authors.forename: G
authors.initials: G
authors.lastname: Masera
authors.forename: A
authors.initials: A
authors.lastname: Biondi
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000483:Alleles; D001803:Blood Transfusion; D004920:Erythropoiesis; D005796:Genes; D005808:Genes, Recessive; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008970:Molecular Weight; D010949:Plasma; D012333:RNA, Messenger / Q000096:biosynthesis; D014168:Transferrin / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D012333:RNA, Messenger; D014168:Transferrin