Ferritin light chain gene mutations in two Brazilian families with hereditary hyperferritinemia-cataract syndrome. These mutations cause the ferritin levels to increase even in the absence of iron overload. Patients also develop bilateral cataract early due to accumulation of ferritin in the lens, and many are misdiagnosed as having hemochromatosis and thus not properly treated.
The first cases were described in and several mutations have already been identified. However, this syndrome is still a poorly understood. We report two cases of unrelated Brazilian families with clinical suspicion of the syndrome, which were treated in our department. Single nucleotide polymorphism-like mutations were found in the affected patients, previously described. The test assisted in making the accurate diagnosis of the disease, and its description is important so that the test can be incorporated into clinical practice.
Ferritin is a protein composed of two fundamental subunits light and heavy chains and it is responsible for the storage of iron within cells. Under normal conditions, serum ferritin concentration is used in the evaluation of iron stores and also as an acute phase protein marker. When the intracellular iron concentration is low, the iron-regulating protein binds to a specific sequence in the iron-responsive element, which folds forming a loop, preventing translation of the messenger RNA.
When iron is available in the cell, it binds to the iron-regulating protein, inducing its dissociation from the iron-responsive element and allowing the translation of the messenger RNA to form the ferritin light chain. Some specific mutations in the iron-responsive element prevent it to bind to the iron-regulating protein, leading to a continuous synthesis of the FTL gene and consequently to high levels of ferritin in the absence of iron overload.
The first case reports of this syndrome were published in by two groups, in Italy and France. Patients with this syndrome often develop early bilateral cataract due to accumulation of ferritin in the lens. The most frequent laboratory findings in these patients are elevated ferritin, and normal levels of serum iron and transferrin saturation.
