Hereditary hyperferritinaemia cataract syndrome

How should hyperferritinaemia be investigated and managed?

“…These individuals have hyperferritinaemia with normal or low TS, and early onset of cataracts due to precipitation of ferritin in the lens [67]. The cataracts may be asymptomatic but can be diagnosed in children [68,69].…”

A Novel Phenotype of a Hereditary Hemochromatosis Type 4 with Ferroportin-1 Mutation, Presenting with Juvenile Cataracts

“…Arthropathy is not an unusual symptom in HDIM. In a previous report, 16% of patients with type 4 HH were found to have arthropathy (7), compared with 24% in type 1 HH (17) and 10% in HHCS (11). In type 1 HH, arthropathy is usually persistent, refractory to phlebotomy, and structurally irreversible, becoming more common with increasing age and ferritin concentration.…”

“…HHCS is an autosomal dominant disorder associated with hyperferritinemia and the onset of cataracts in early life, characterized by ferruginous cataracts without systemic iron deposition with a normal serum iron concentration and TSAT, and caused by mutations in the 5'-iron-regulatory element upstream of FTL mRNA which cause dysregulation of FTL biosynthesis. Thirty-seven mutations have been associated with HHCS since it was first reported in 1995 (11). Among disorders with hyperferritinemia, juvenile cataracts are not found with any other disorders except HHCS.…”

“…As both the present case and cases of HHCS share common traits of hyperferritinemia and juvenile cataract, a similar mechanism may explain the early cataract formation. In HHCS, unbalanced formation of FTL causes free polypeptides to precipitate as crystallin inclusions in the lens stroma, leading to the formation of cataracts (11), while in cases of a mutation of IRE in FTH, tissue iron depositions without cataracts are observed (12). Physiologically, FTL facilitates iron-core formation, whereas FTH generates ferroxidase activity that appears to be essential for incorporation of iron into the protein shell (13).…”

Simultaneous presentation of hereditary hyperferritinaemia cataract syndrome and hereditary haemochromatosis

“…Since first described in 1995, there have been 37 variants reported in the IRE of the FTL gene associated with HHCS . The high ferritin levels do not cause any clinical symptoms apart from those due to cataract, and there are no other known clinical or pathological manifestations of HHCS . Individuals with HHCS are often misdiagnosed as having haemochromatosis due to high ferritin levels and often undergo inappropriate venesection that can lead to iron deficiency.…”