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

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 12; no. 1; p. 17
• Main Authors: Cadenas, Beatriz, Fita-Torró, Josep, Bermúdez-Cortés, Mar, Hernandez-Rodriguez, Inés, Fuster, José Luis, Llinares, María Esther, Galera, Ana María, Romero, Julia Lee, Pérez-Montero, Santiago, Tornador, Cristian, Sanchez, Mayka
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23-01-2019; MDPI
• Subjects: Anemia; Cataracts; cataracts syndrome; ferritin; Hematology; hereditary hyperferritinemia; hereditary hypoferritinemia; Hospitals; Iron; iron metabolism; Mutation; neurodegenerative disease; Neutropenia; Pediatrics; Proteins; iron metabolism; cataracts syndrome; hereditary hypoferritinemia; ferritin; neurodegenerative disease; hereditary hyperferritinemia
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph12010017

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 (
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
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
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
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
gene.