Raised serum ferritin concentration in hereditary hyperferritinemia cataract syndrome is not a marker for iron overload.
Bottom Line: Hyperferritinemia and bilateral cataracts are features of the rare hereditary hyperferritinemia cataract syndrome (HHCS; OMIM #600886).HHCS is an autosomal dominant condition caused by mutations which increase expression of the ferritin light polypeptide (FTL) gene.We report a patient with HHCS who was misdiagnosed and treated as having hemochromatosis, in whom a heterozygous c.-160A>G mutation was identified in the iron responsive element (IRE) of FTL, causing ferritin synthesis in the absence of iron overload.
Affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology (HUST), Wuhan, P.R. China; Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, UCL, London, UK.Show MeSH
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Mentions: A 43-year-old Caucasian man was hospitalized following exposure to formaldehyde. His hemoglobin, serum iron concentration, total iron binding capacity (TIBC), and transferrin saturation were within the laboratory reference ranges but his serum ferritin concentration was elevated (1650 μg/L; reference range 25-300 μg/L). Serum transaminase activities, copper, ceruloplasmin, and lead concentrations were normal. A liver biopsy showed normal liver architecture and no evidence of iron overload. There was no history of alcohol abuse. He did, however, have a family history of hemochromatosis in a pattern suggestive of autosomal dominant inheritance (Fig. 1A) and a personal history of bilateral rheumatoid factor negative arthritis affecting his ankles and knees which had resolved spontaneously after 6 months and of bilateral cataract removal the previous year. A diagnosis of hemochromatosis was made on the basis of the strong family history and the presence of persistent hyperferritinemia despite the absence of evidence of iron overload. Venesection (450 mL) was performed monthly for 6 months but was stopped when the patient became symptomatic with a microcytic, iron deficient anemia in the absence of any other source of bleeding; at this time his hemoglobin was 10.0 g/dL (12.5-17.5 g/dL), transferrin saturation 4% (20%-55%) while his serum ferritin remained elevated at 1,728 μg/L. Venesection was stopped; he was treated with iron supplements until he was iron replete; his serum ferritin concentrations remained elevated throughout.
Affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology (HUST), Wuhan, P.R. China; Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, UCL, London, UK.