Neonatal hemochromatosis is an enigmatic disease. Little is known about
iron metabolism in this disease, including the tissue concentration of
ferritin or its H and L subunit ratio. The authors report the tissue
iron,
ferritin, and
ferritin subunit content of a child who died at 5 weeks of
neonatal hemochromatosis. The child was born at 29 weeks gestation to a mother with lupus,
sickle cell trait, and
gestational diabetes. The child's severe
liver dysfunction led to the clinical diagnosis of
neonatal hemochromatosis at 1 week of age. Despite aggressive support, including red cell transfusions and chelation, the child died of an
intracranial hemorrhage. Autopsy showed
liver fibrosis and
iron staining characteristic of
neonatal hemochromatosis. Autopsy liver tissue was compared to age-matched control tissue. Soluble
protein was analyzed by the Bradford method. Soluble
iron (over 90% of total
iron) was analyzed by the
o-phenanthroline complex. Tissue
ferritin and human
ferritin controls (Calzyme) were analyzed by Western blotting after SDS-PAGE, identified with sheep anti-human
ferritin antibodies (The BindingSite) secondary antibody-fluorescence for detection, and quantified using the Molecular Dynamics Storm 840 phosphorimager and ImageQuant software.
Protein,
iron, and total
ferritin were similar in the normal and
neonatal hemochromatosis liver tissues.
Ferritin subunits, however, showed an increased H/L-subunit ratio compared to an age-matched control. This first report of a marked increase in the
ferritin H/L-subunit ratio may point to an underlying mechanism of disease in this enigmatic disorder.