A Portuguese patient homozygous for the -25G>A mutation of the HAMP promoter shows evidence of steady-state transcription but fails to up-regulate hepcidin levels by iron.

Blood. 2005 Oct 15;106(8):2922-3. A Portuguese patient homozygous for the -25G>A mutation of the HAMP promoter shows evidence of steady-state transcription but fails to up-regulate hepcidin levels by iron. Porto G, Roetto A, Daraio F, Pinto JP, Almeida S, Bacelar C, Nemeth E, Ganz T, Camaschella C. PMID: 16204153 [PubMed - indexed for MEDLINE]Free Article Publication Types, MeSH Terms, SubstancesPublication Types: Letter Research Support, Non-U.S. Gov't MeSH Terms: Antimicrobial Cationic Peptides/genetics* Antimicrobial Cationic Peptides/urine Glycine/genetics* Hemochromatosis/genetics Homozygote* Humans Iron/pharmacology* Mutation/genetics Portugal Promoter Regions, Genetic/genetics* Transcription, Genetic/genetics* Up-Regulation/drug effects* Substances: Antimicrobial Cationic Peptides hepcidin Glycine Iron LinkOut - more resourcesFull Text Sources: HighWire Press EBSCO Other Literature Sources: COS Scholar Universe Medical: Genetics Home Reference - HAMP Gene - Genetics Home Reference Molecular Biology Databases: IRON - HSDB GLYCINE - HSD

Growth hormone (GH)‐induced reconstitution of CD8+ CD28+ T lymphocytes in a rare case of severe lymphopenia associated with Juvenile Haemochromatosis and Turner's syndrome.

Clin Endocrinol (Oxf). 2004 Oct;61(4):437-40. Growth hormone (GH)-induced reconstitution of CD8+ CD28+ T lymphocytes in a rare case of severe lymphopenia associated with Juvenile Haemochromatosis and Turner's syndrome. Porto G, Cruz E, Miranda HP, Porto B, Vasconcelos JC, Lacerda R, Roetto A, Daraio F, Bacelar C. Santo António General Hospital, Porto, Portugal. [email protected] Abstract This paper describes a rare case of Turner's syndrome associated with Juvenile Haemochromatosis and severe lymphopenia, followed-up for a period of 5 years. Because of the indication for treatment with growth hormone (GH), this case was observed as a model to analyse the effects of GH on growth, iron mobilization and lymphocyte reconstitution. For this purpose, a serial study of the T lymphocyte subpopulations CD4+, CD8+, CD8+ CD28+ and CD8+ CD28- was performed by immunophenotyping during the follow-up period. Besides the impact of both phlebotomy treatment and GH on the rapid growth and mobilization of 20.8 g of iron in 136 weeks, the most relevant observation was the finding of a significant expansion of CD8+ T lymphocytes expressing the costimulatory marker CD28 in the setting of the severe lymphopenia. These findings constitute new clinical evidence supporting the notion that the GH/IGF-1 system has an important role on the maintenance of T cell homeostasis in vivo, and that GH may be regarded as a putative therapeutic agent in T lymphocyte reconstitution. PMID: 15473875 [PubMed - indexed for MEDLINE

Activation of the Hepcidin-Ferroportin1 pathway in the brain and astrocytic–neuronal crosstalk to counteract iron dyshomeostasis during aging

During physiological aging, iron accumulates in the brain with a preferential distribution in regions that are more vulnerable to age-dependent neurodegeneration such as the cerebral cortex and hippocampus. In the brain of aged wild-type mice, alteration of the Brain Blood Barrier integrity, together with a marked inflammatory and oxidative state lead to increased permeability and deregulation of brain-iron homeostasis. In this context, we found that iron accumulation drives Hepcidin upregulation in the brain and the inhibition of the iron exporter Ferroportin1. We also observed the transcription and the increase of NCOA4 levels in the aged brain together with the increase of light-chain enriched ferritin heteropolymers, more efficient as iron chelators. Interestingly, in cerebral cortex and hippocampus, Ferroportin1 is mainly expressed by astrocytes, while the iron storage protein ferritin light-chain by neurons. This differential distribution suggests that astrocytes mediate iron shuttling in the nervous tissue and that neurons are unable to metabolize it. Our findings highlight for the first time that Hepcidin/Ferroportin1 axis and NCOA4 are directly involved in iron metabolism in mice brain during physiological aging as a response to a higher brain iron influx

A child with hyperferritinemia: Case report

Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare condition caused by mutations in the gene coding for the light chain of ferritin; it does not lead to iron overload, but it is associated with the risk of developing a bilateral nuclear cataract also in childhood. On the contrary, a raise of serum ferritin levels is a common finding in pediatrics. We describe here a case of HHCS that offers some interesting clues for the daily practice. Our patient is a 6 year old Italian boy who came to our attention after some time of diagnostic uncertainties because of persistently high levels of ferritin with no apparent cause. We were guided to the suspect of this syndrome by the family history (5 members with various degrees of cataract developed in first infancy). High levels of serum ferritin and specific genetic testing (mutation A37C) confirmed the diagnosis. This case underlines the need of considering rare genetic syndromes, including hereditary hyperferritinemia cataract syndrome, in the differential diagnosis of raised serum ferritin in children and the importance of paying attention to family history in considering a patient with isolated raised levels of serum ferritin