Iron overload and prolonged ingestion of iron supplements: Clinical features and mutation analysis of hemochromatosis‐associated genes in four cases

Barton, James C.; Lee, Pauline L.; West, Carol; Bottomley, Sylvia S.

doi:10.1002/ajh.20714

Cited by 36 publications

(22 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…45 A man who took daily ferrous sulfate for beta-thalassemia minor (153 g of Fe over 7 years) was subsequently diagnosed to have hemochromatosis, C282Y homozygosity, and diabetes mellitus; 32 g of iron was removed by phlebotomy to achieve iron depletion. 80 Urinary hepcidin levels did not increase in C282Y homozygotes given a single 65 mg of iron dose as ferrous sulfate, regardless of their state of iron depletion by therapeutic phlebotomy. 81 Although 27% of †Nonferrous metals including cobalt, zinc, manganese, and chromium share absorptive pathways with iron; excess zinc and manganese are retained in the liver.…”

Section: Ironmentioning

confidence: 90%

How I treat hemochromatosis

Adams

Barton

2010

Blood

Self Cite

159

167

View full text Add to dashboard Cite

Hemochromatosis is a common genetic disorder in which iron may progressively accumulate in the liver, heart, and other organs. The primary goal of therapy is iron depletion to normalize body iron stores and to prevent or decrease organ dysfunction. The primary therapy to normalize iron stores is phlebotomy. In this opinion article, we discuss the indications for and monitoring of phlebotomy therapy to achieve iron depletion, maintenance therapy, dietary and pharmacologic maneuvers that could reduce iron absorption, and the role of voluntary blood donation. (Blood. 2010;116(3):317-325)

show abstract

Section: Ironmentioning

confidence: 90%

How I treat hemochromatosis

Adams

Barton

2010

Blood

Self Cite

159

167

View full text Add to dashboard Cite

show abstract

“…Some have hemochromatosis-associated mutations and mild or no anemia; phlebotomy therapy is feasible and effective in these patients and would prevent complications of iron overload [48]. For patients with anemia that precludes phlebotomy, it is reasonable to use chelation therapy in a manner similar to that recommended for -thalassemia or sickle cell disease.…”

Section: Iron Overload Due To Iron Supplementsmentioning

confidence: 99%

Chelation therapy for iron overload

Barton¹

2007

Curr Gastroenterol Rep

Self Cite

View full text Add to dashboard Cite

Iron overload is characterized by excessive iron deposition and consequent injury and dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Because physiologic mechanisms to excrete iron are very limited, patients with iron overload and its complications need safe, effective therapy that is compatible with their coexisting medical conditions. The availability of three licensed iron chelation drugs (one parenteral, two oral) and the development and clinical investigation of other oral chelators represent new opportunities to prevent or manage iron overload in patients with heritable types of severe anemia, such as beta-thalassemia major and sickle cell disease, and for the formulation of alternatives to phlebotomy therapy for patients with iron overload associated with the HFE gene and other adult age-of-onset types of hemochromatosis, African iron overload, and African-American iron overload.

show abstract

“…In 213 screening p.C282Y homozygotes, no significant relationship between reports of supplemental iron use and SF levels was found [32]. In an unusual case, a man with hemochromatosis, p.C282Y homozygosity, and β-thalassemia minor who ingested ferrous sulfate tablets daily absorbed much iron [33].…”

Section: Discussionmentioning

confidence: 95%

GNPAT p.D519G is Independently Associated with Markedly Increased Iron Stores in HFE p.C282Y Homozygotes

Barton

Chen

Emond

et al. 2016

Blood

Self Cite

View full text Add to dashboard Cite

GNPAT (chromosome 1q42.2) encodes the peroxisomal enzyme glyceronephosphate O-acyltransferase. In a previous study, DNA of men with hemochromatosis and HFE p.C282Y homozygosity and either markedly increased iron stores or normal or mildly increased iron stores were evaluated with exome sequencing. Positivity for the GNPAT polymorphism p.D519G (rs11558492) was significantly greater in men with markedly increased iron stores (McLaren CE et al., Hepatology 2015;62:429-39). This result suggests that the p.D519G is a candidate modifier of iron phenotypes in p.C282Y homozygotes. To learn more, we examined associations of p.D519G, age, iron-related variables, and daily alcohol consumption with iron stores in p.C282Y homozygotes classified by extremes of iron overload phenotypes. We defined markedly increased iron stores as serum ferritin >1000 µg/L and either hepatic iron >236 µmol/g dry weight or mobilizable iron >10 g by induction phlebotomy (men and women). Normal or mildly elevated iron stores were defined as serum ferritin <300 µg/L and either age ≥40 y with ≤2.5 g iron removed by induction phlebotomy or age ≥50 y with ≤3.0 g iron removed by induction phlebotomy (men only). We first compared general characteristics of participant subgroups using univariate methods. Then, using multivariable logistic regression, we evaluated associations of markedly increased iron stores with the following six variables observed at diagnosis of hemochromatosis that might account for markedly increased iron stores: age; iron supplement use (dichotomous); number of whole blood units donated; number of erythrocyte units received as transfusion; daily alcohol consumption, g; and p.D519G positivity (heterozygosity or homozygosity). There were 56 participants (53 men, 3 women), of whom 41 (38 men, 3 women) had markedly increased iron stores and 15 others had normal or mildly increased iron stores (all men). The mean age of the 56 participants was 55 ± 10 (SD) y. Prevalences of swollen/tender 2nd/3rd metacarpophalangeal joints and elevated serum levels of aspartate or alanine aminotransferase were significantly greater in participants with markedly increased iron stores. Only participants with markedly increased iron stores had cirrhosis proven by biopsy. Odds ratios of having markedly increased iron stores for each of the six variables, as determined by univariate logistic regression, are displayed in Table 1. In the multivariable analysis, p.D519G positivity was the only exposure variable significantly associated with markedly increased iron stores (odds ratio 9.9, 95% CI [1.6, 60.3], p = 0.0126). Area under the curve for the multivariable logistic regression analysis was 0.82. We conclude that GNPAT p.D519G is strongly associated with markedly increased iron stores in p.C282Y homozygotes after correction for age, iron-related variables, and daily alcohol consumption. It remains unknown whether p.D519G directly enhances iron transport into the blood by absorptive enterocytes, indirectly augments iron absorption by suppressing hepcidin, or is linked to a putative iron absorption promoter on chromosome 1q. Disclosures No relevant conflicts of interest to declare.

show abstract

Iron overload and prolonged ingestion of iron supplements: Clinical features and mutation analysis of hemochromatosis‐associated genes in four cases

Cited by 36 publications

References 51 publications

How I treat hemochromatosis

How I treat hemochromatosis

Chelation therapy for iron overload

GNPAT p.D519G is Independently Associated with Markedly Increased Iron Stores in HFE p.C282Y Homozygotes

Contact Info

Product

Resources

About