Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary iron overload may be relatively common in African Americans, but its cause is incompletely understood. Thus, we evaluated genotype and phenotype characteristics of unselected African American index patients with primary iron overload who reside in central Alabama. All had hepatic iron concentration > or =30 micromol/g dry wt or > or =2.0 g of iron mobilized by phlebotomy to achieve iron depletion. Genotype analyses were performed in African American control subjects from the same region. There were 23 patients (19 men, 4 women); mean age at diagnosis was 52 +/- 12 years (1 SD) (range 32-69 years). Nine (39.1%) reported that they consumed > or =45 g of ethanol daily; five had chronic hepatitis C. Eight had some form of hemoglobinopathy or thalassemia. Mean serum transferrin saturation was 56 +/- 28% (range 15-100%). The geometric mean serum ferritin at diagnosis was 1076 ng/mL [95% confidence interval 297-3473 ng/mL]. Increased stainable liver iron was observed in hepatocytes only in 4 patients, in macrophages only in 8 patients, and in hepatocytes and macrophages in 8 patients. The mean quantity of iron mobilized by phlebotomy (corrected for iron absorbed during treatment) was 5.3 +/- 2.0 g (range 4.0-8.4 g). Iron removed by phlebotomy was greater in patients with hemoglobinopathy or thalassemia than in those without these forms of anemia (6.6 +/- 1.3 g vs 3.9 +/- 1.6 g, respectively; P = 0.0144). Daily consumption of > or =45 g of ethanol or chronic hepatitis C was not associated with an increased or decreased amount of phlebotomy-mobilized iron, on the average. The percentage of index patients positive for HFE C282Y was greater than that of controls (P = 0.0058). The respective percentages of phenotype positivity for HFE H63D, D6S105(8), and HLA-A*03 were similar in patients and controls. HFE S65C, I105T, and G93R were not detected in index or control subjects. Two of 13 patients were heterozygous for the ferroportin allele nt 744 G-->T (Q248H), although the phenotype frequency of this allele was similar in patients and 39 controls. Synonymous ferroportin alleles were also detected in some patients. The ceruloplasmin mutation nt 1099C-->T (exon 6; Arg367Cys) was detected in 1 of 2 patients tested. Abnormal alleles of beta-2 microglobulin, Nramp2, TFR2, hepcidin, or IRP2 alleles were not detected in either of the 2 patients so tested. We conclude that primary iron overload in African Americans is not the result of the mutation of a single gene. HFE C282Y, ferroportin 744 G-->T, and common forms of heritable anemia appear to account for increased iron absorption or retention in some patients.
 ...
PMID:Genotypic and phenotypic heterogeneity of African Americans with primary iron overload. 1463 44

Calprotectin, also known as the S100A8/A9 or MRP8/14 complex, is a major calcium-binding protein in the cytosol of neutrophils, monocytes, and keratinocytes. It differs from other S100 proteins in its zinc-binding capacity. The authors describe a 4-year-old girl with severe anemia, neutropenia, inflammation, and severe growth failure. Bone marrow examination showed moderate dyserythropoiesis. No hemolysis, iron deficiency, hemoglobinopathies, immunologic diseases, or autoantibodies were detected. Serum levels of copper and ceruloplasmin were within the normal range, although the serum zinc concentration was markedly increased (310 microg/dL). Urinary zinc excretion and erythrocyte zinc concentrations were within the normal range. Family studies showed normal zinc and copper plasma levels. The patient's plasma calprotectin concentration showed a 6,000-fold increase (2,900 mg/L) compared with normal values. The calprotectin concentration is known to be elevated in many inflammatory conditions but is generally below 10 mg/L and thus far below the levels reported in this patient. The authors describe this case as an inborn error of zinc metabolism caused by dysregulation of calprotectin metabolism, which mainly presented with the features of microcytic anemia and inflammation.
 ...
PMID:Severe anemia and neutropenia associated with hyperzincemia and hypercalprotectinemia. 1618 40

One of the hallmarks of both sickle cell disease (SCD) and thalassemia major (TM) is accelerated oxidative damage. Decreased antioxidant levels and increased oxidant stress biomarkers are found in both diseases. Although isolated vitamin deficiencies have been reported in TM and nontransfused SCD patients, a comprehensive evaluation of vitamin and trace mineral levels has never been performed in chronically transfused SCD or TM patients. As vitamins and trace minerals may be consumed as a result of chronic oxidative stress; we hypothesized that levels of these compounds would correlate with surrogates of iron overload, hemolysis, and inflammation in chronically transfused patients. Using a convenience sample of our group of chronically transfused patients we studied 43 patients with SCD (17 male, 26 female) and 24 patients with TM (13 male and 11 female). The age range for our patients varied from 1.5 to 31.4 years. Levels of vitamins A, thiamin, B6, B12, C, D, E as well as selenium, zinc, copper, and ceruloplasmin were measured. We found that 40-75% of the patients were deficient in A, C, D and selenium and 28-38% of the patients had low levels of B vitamins and folate. There was little association with iron overload, hemolysis, or inflammation. Although the precise mechanism of these deficiencies is unclear, they may contribute to the morbidity of chronically transfused hemoglobinopathy patients.
 ...
PMID:Nutritional deficiencies in iron overloaded patients with hemoglobinopathies. 1941 22