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Liver ferritin subunit ratios in neonatal hemochromatosis
Ward Hagar1, Elliott P Vichinsky, Elizabeth C Theil
1Children's Hospital, Oakland, Research Institute, Oakland, California 95609, USA. whagar@mail.cho.org
Insights
Neonatal hemochromatosis, a rare iron disorder, shows a significantly increased ferritin H/L-subunit ratio in affected infants. This finding offers new insights into the disease's underlying iron metabolism mechanisms.
Area of Science:
- Pediatric Pathology
- Biochemistry
- Neonatal Medicine
Background:
- Neonatal hemochromatosis is a severe, poorly understood iron metabolism disorder in newborns.
- Limited knowledge exists regarding iron distribution and ferritin composition in affected tissues.
Observation:
- A case study examined liver tissue from a 5-week-old infant with neonatal hemochromatosis.
- Tissue iron, total ferritin, and protein levels were comparable to age-matched controls.
- A notable increase in the ferritin H/L-subunit ratio was observed in the infant's liver tissue.
Findings:
- The study identified a significantly elevated H/L-subunit ratio of ferritin in neonatal hemochromatosis liver tissue.
- This ratio differed markedly compared to control liver tissue from healthy infants.
Implications:
- The altered ferritin subunit ratio may indicate a novel mechanism contributing to iron dysregulation in neonatal hemochromatosis.
- This discovery could pave the way for future research into the pathogenesis and potential therapeutic targets for this enigmatic disease.
Abstract:
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.