Hereditary hyperferritinemia-cataract syndrome

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare genetic disorder characterized by elevated serum ferritin levels and early-onset bilateral cataracts. It is caused by mutations in the iron-responsive element (IRE) located in the 5' untranslated region of the FTL gene (ferritin light chain gene) on chromosome 19q13. These mutations disrupt the normal regulation of ferritin light chain production, leading to overproduction and accumulation of ferritin in the lens of the eye and elevated ferritin levels in the blood. Importantly, despite the high serum ferritin levels — which can range from 1,000 to over 2,000 µg/L — patients do not have iron overload, and iron studies such as transferrin saturation remain normal. The hallmark clinical features are persistently elevated serum ferritin and bilateral cataracts that typically develop in childhood or early adulthood, though they may be present from birth. The cataracts are caused by crystalline deposits of ferritin light chain (L-ferritin) within the lens and tend to be progressive, often described as having a distinctive 'breadcrumb' or 'sunflower' pattern on slit-lamp examination. Vision impairment varies from mild to significant, depending on the severity and location of the lens opacities. A major clinical concern is that patients are frequently misdiagnosed with hemochromatosis due to the elevated ferritin and may undergo unnecessary phlebotomy or liver biopsy, which can lead to iron deficiency anemia. There is no specific medical treatment to prevent or reverse the cataracts in HHCS. Management is primarily surgical, with cataract extraction performed when visual impairment becomes functionally significant. Cataracts may recur after surgery if lens material remains. Genetic counseling is important for affected families. Awareness of this condition among clinicians is essential to avoid inappropriate treatment for presumed iron overload. The prognosis is generally good, as the condition does not cause organ damage related to iron deposition.

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