Anemia and iron overload due to compound heterozygosity for novel ceruloplasmin mutations.
Aceruloplasminemia is a recessive disorder characterized by anemia, iron overload, and neurodegeneration, caused by the absence of ceruloplasmin (Cp), a multicopper oxidase important for iron export. Few patients homozygous for loss of function mutations of the Cp gene have been reported. We describe a 62-year-old white woman with heavy liver iron overload, diabetes, anemia, and neurologic symptoms. She was compound heterozygote for 2 novel mutations that result in the absence of hepatocyte Cp: an adenine insertion at nucleotide 2917 causing a truncated protein and a C-G transversion causing a glutamine-->glutamic acid substitution at position 146. Although rare in whites, aceruloplasminemia should be considered in the differential diagnosis of unexplained anemia associated with iron overload, because these features anticipate progressive neurologic symptoms. We propose that anemia, secondary to the impaired macrophage iron release, plays a major role in hepatic iron overload through increased absorption mediated by the erythroid regulator.
Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Azienda Ospedaliera San Luigi, 10043-Orbassano, Turin, Italy.
Sandra
S
Bosio
Marco
M
De Gobbi
Antonella
A
Roetto
Gabriella
G
Zecchina
Eugenio
E
Leonardo
Mario
M
Rizzetto
Claudio
C
Lucetti
Lucia
L
Petrozzi
Ubaldo
U
Bonuccelli
Clara
C
Camaschella
D000740:Anemia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002570:Ceruloplasmin / Q000235:genetics*; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005192:Family Health; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D019190:Iron Overload / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000209:etiology
D002570:Ceruloplasmin