&lt;b&gt;&lt;i&gt;HAMP&lt;/i&gt;&lt;/b&gt; Gene Mutation Associated with Juvenile Hemochromatosis in Brazilian Patients

Fonseca, Paula Fernanda Silva; Cançado, Rodolfo Delfini; Lopes, Marly Maria Uellendahl; Correia, Edileide de Barros; Lescano, Manuel; Santos, Paulo Caleb Júnior Lima

doi:10.1159/000444119

Cited by 8 publications

(5 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nucleotide substitutions and insertion/deletion mutations are widespread in the coding region and 5 0 -UTR of the HAMP gene [26][27][28]. Most mutations cause amino acid replacements, shortened proteins, or shifts in the reading frame, leading to reduced serum hepcidin and increased FPN levels within epithelial cells of the small intestine.…”

Section: Hamp Genementioning

confidence: 99%

Reciprocal regulation between hepcidin and erythropoiesis and its therapeutic application in erythroid disorders

Wang

Zheng

Zhu

et al. 2017

Experimental Hematology

View full text Add to dashboard Cite

Iron is required for hemoglobin production, and it plays a key role during erythropoiesis. Systemic iron homeostasis is mainly negatively regulated by the peptide hormone hepcidin, coded by the gene HAMP. Hepcidin excess may cause iron deficiency, iron-restricted erythropoiesis, and anemia. Conversely, hepcidin insufficiency leads to iron overload and oxidative damage in multiple tissues. During regulation of hepcidin synthesis, multiple promoter elements in the HAMP gene respond to variable signaling pathways corresponding to different extracellular situations. It has been reported that hepcidin expression can be suppressed by secreted erythroid factors, including GDF15, TWSG1, GDF11, and ERFE, thereby increasing iron availability for hemoglobin synthesis. These potential erythroid factors act via intricate mechanisms that remain controversial. However, it is clear that hepcidin affects erythropoiesis, and promising therapies targeting hepcidin have been developed to treat erythroid disorders. These therapeutic strategies include suppressing or activating HAMP gene expression, mimicking or activating hepcidin activity, and blocking the ability of hepcidin to bind to its target ferroportin.

show abstract

Section: Hamp Genementioning

confidence: 99%

Reciprocal regulation between hepcidin and erythropoiesis and its therapeutic application in erythroid disorders

Wang

Zheng

Zhu

et al. 2017

Experimental Hematology

View full text Add to dashboard Cite

show abstract

“…When compared with HFE -hemochromatosis, the frequency of the JH condition with HAMP gene mutation is considered very rare. However, some cases were reported[ 5 , 6 ]. Here, we report one case of a Brazilian patient with JH condition due to HAMP mutation (g.47G>A), first identified in a Portuguese family[ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Juvenile hemochromatosis: HAMP mutation and severe iron overload treated with phlebotomies and deferasirox

Lescano¹,

Tavares

Santos

2017

WJCC

View full text Add to dashboard Cite

Juvenile hemochromatosis (JH) is a rare condition classified as an autosomal recessive disorder that leads to severe iron absorption. JH usually affects people under the age of 30 and presents symptoms such as chronic liver damage, hypogonadotropic hypogonadism, cardiac diseases and endocrine dysfunctions. The present case reports a 29-year-old Brazilian woman with JH condition due to HAMP mutation (g.47G>A), treated with phlebotomies and deferasirox. She presented symptoms such as weakness, skin hyperpigmentation, joint pain in the shoulders and hands and amenorrhea. First laboratory tests showed altered biochemical parameters [serum ferritin (SF): 5696 ng/mL, transferrin saturation (TS): 85%]. After sessions of phlebotomies (450 mL every 15 d), the patient presented partial symptomatic improvements and biochemical parameters (SF: 1000 ng/mL, Hb: 11 g/dL). One year later, deferasirox (15 mg/kg per day) was introduced to the treatment, and the patient showed total symptomatic improvement, with significant clearing of the skin, SF: 169 ng/mL, and TS: 50%. Furthermore, after the combined deferasirox-phlebotomy therapy, magnetic resonance imaging measurements revealed normalized level for liver iron (30 μmol/g; reference value < 36 μmol/g). In conclusion, combined deferasirox-phlebotomy treatment was able to normalize iron levels and improve symptoms.

show abstract

“…Otherwise, the exclusion criteria were: patients with positive serology for hepatitis (B or C), alcoholic liver disease, high alcoholic consumption (more than 20 g daily), hemolytic anemias, repeated blood transfusions, metabolic syndrome, or insulin resistance not resulting from hemochromatosis. In this study, we also excluded patients with juvenile hemochromatosis carrying HAMP and HJV mutations [ 14 , 15 ].…”

Section: Methodsmentioning

confidence: 99%

Quality of Life Scores Remained Different among the Genotypic Groups of Patients with Suspected Hemochromatosis, Even after Treatment Period

Acevedo

Alvarenga

Fonseca

et al. 2022

Genes

Self Cite

View full text Add to dashboard Cite

Background: Hemochromatosis is a genetic condition of iron overload caused by deficiency of hepcidin. In a previous stage of this study, patients with suspected hemochromatosis had their quality of life (QL) measured. We observed that QL scores differed among genotypic groups of patients. In this reported final phase of the study, the aims were to compare QL scores after a treatment period of approximately 3 years and to analyze a possible association of the serum ferritin values with QL scores. Methods: Sixty-five patients were enrolled in this final phase and divided into group 1 (patients that showed primary iron overload and homozygous genotype for the HFE p.Cys282Tyr mutation) and group 2 (other kinds of genotypes). Short Form 36 (SF-36) was performed and consisted of eight domains with a physical and also a mental component. Results: Both groups had a significant decrease in serum ferritin concentrations: group 1 had a variation from 1844 ± 1313 ng/mL to 281 ± 294 ng/mL, and group 2 had a variation from 1216 ± 631 ng/mL to 236 ± 174 ng/mL. Group 1 had a smaller mean value for these six SF-36 domains compared with group 2, indicating a worse QL. Conclusions: In this final stage, six domains demonstrated a difference among genotypic groups (role emotional and mental health, adding to the four of the initial phase), reassuring the impact of the identified genotype on the QL of hemochromatosis patients. Furthermore, despite that both patient groups demonstrated similar and significant decreases in serum ferritin values, no association was found between the decrease in this biological parameter and the SF-36 domains.

show abstract

<b><i>HAMP</i></b> Gene Mutation Associated with Juvenile Hemochromatosis in Brazilian Patients

Cited by 8 publications

References 16 publications

Reciprocal regulation between hepcidin and erythropoiesis and its therapeutic application in erythroid disorders

Reciprocal regulation between hepcidin and erythropoiesis and its therapeutic application in erythroid disorders

Juvenile hemochromatosis: HAMP mutation and severe iron overload treated with phlebotomies and deferasirox

Quality of Life Scores Remained Different among the Genotypic Groups of Patients with Suspected Hemochromatosis, Even after Treatment Period

Contact Info

Product

Resources

About