Ferritin is the protein responsible for the storage and intracellular distribution of iron. It consists of two subunits called L-ferritin and H-ferritinL. The synthesis of these subunits is controlled by a regulatory proteins called Iron-regulatory proteins (IRPs) that bind to a regulatory element called iron-responsive element (IRE) present in the 5'UTR of mRNA of each of these two subunits.
In 1995 the Hereditary Hyperferritinemia Cataract Syndrome (HHCS) (OMIM # 600886) was first described. It is characterized by elevated levels of serum ferritin without iron overload, congenital cataracts and autosomal dominant inheritance. Excessive production of ferritin is due to mutations in the regulatory element called Iron-responsive element (IRE) light chain gene-ferritin L (FTL).
Ferritin excess accumulates in the lens which leads to the development of cataracts. The degree of affectation varies even between individuals with the same mutation. A correct genetic diagnosis of this disease is important, as it is often confused with hereditary hemochromatosis due to the high levels of serum ferritin present in both diseases.
The overproduction of serum ferritin may also be due to mutations in the coding sequence of the gene for L-ferritin. In 2009 Kannengiesser and colleagues described a new form of genetic hyperferritinemia, known as benign hyperferritinemia without iron overload, with dominant inheritance (Kannengiesser C, et al. Haematologica. 2009).
In 2001, Kato and colleagues described a mutation of the regulatory element IRE (iron-responsive element) located in the 5 'UTR of the gene for ferritin-H (fth1) in a Japanese family with an iron overload syndrome and pattern of dominant inheritance (Kato et al. Am. J. Hum. Genet. 69:191-197, 2001) (OMIM # 134770). According to this study, this mutation produces iron overload in liver, pancreas and heart, and elevated serum iron and ferritin.