L-Ferritin: One Gene, Five Diseases; from Hereditary Hyperferritinemia to Hypoferritinemia-Report of New Cases

• Main Authors: Beatriz Cadenas (Author), Josep Fita-Torró (Author), Mar Bermúdez-Cortés (Author), Inés Hernandez-Rodriguez (Author), José Luis Fuster (Author), María Esther Llinares (Author), Ana María Galera (Author), Julia Lee Romero (Author), Santiago Pérez-Montero (Author), Cristian Tornador (Author), Mayka Sanchez (Author)
• Format: Book
• Published: MDPI AG, 2019-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1424-8247; 10.3390/ph12010017
• Keywords: ferritin; hereditary hyperferritinemia; hereditary hypoferritinemia; iron metabolism; cataracts syndrome; neurodegenerative disease; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 12, Iss 1, p 17 (2019)

Ferritin is a multimeric protein composed of light (L-ferritin) and heavy (H-ferritin) subunits that binds and stores iron inside the cell. A variety of mutations have been reported in the L-ferritin subunit gene (<i>FTL</i> gene) that cause the following five diseases: (1) hereditary hyperferritinemia with cataract syndrome (HHCS), (2) neuroferritinopathy, a subtype of neurodegeneration with brain iron accumulation (NBIA), (3) benign hyperferritinemia, (4) L-ferritin deficiency with autosomal dominant inheritance, and (5) L-ferritin deficiency with autosomal recessive inheritance. Defects in the <i>FTL</i> gene lead to abnormally high levels of serum ferritin (hyperferritinemia) in HHCS and benign hyperferritinemia, while low levels (hypoferritinemia) are present in neuroferritinopathy and in autosomal dominant and recessive L-ferritin deficiency. Iron disturbances as well as neuromuscular and cognitive deficits are present in some, but not all, of these diseases. Here, we identified two novel <i>FTL</i> variants that cause dominant L-ferritin deficiency and HHCS (c.375+2T > A and 36_42delCAACAGT, respectively), and one previously reported variant (Met1Val) that causes dominant L-ferritin deficiency. Globally, genetic changes in the <i>FTL</i> gene are responsible for multiple phenotypes and an accurate diagnosis is useful for appropriate treatment. To help in this goal, we included a diagnostic algorithm for the detection of diseases caused by defects in <i>FTL</i> gene.