Dominant Hemochromatosis Due to N144H Mutation of SLC11A3: Clinical and Biological Characteristics

Njajou, Omer T.; Jong, Gerard de; Berghuis, Bianca; Vaessen, Norbert; Snijders, Pieter J.L.M.; Goossens, Jan P.; Wilson, J.H.P.; Breuning, Martijn H.; Oostra, Ben A.; Heutink, Peter; Sandkuijl, Lodewijk A.; Duijn, Cornelia M. van

doi:10.1006/bcmd.2002.0581

Cited by 38 publications

(15 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…expected to mimic hepcidin deficiency and yield a phenotype similar to classical hemochromatosis, with inappropriately high duodenal absorption of iron, increased transferrin saturation, and iron deposition in hepatocytes. Of 12 reported subjects carrying the N144H mutation, 6 had elevated serum ferritin, and of those, 3 had transferrin saturations Ͼ80% (17). In addition, patients with two other mutations affecting the same residue [N144T (18) and N144D (15)] were described to have high serum ferritin and transferrin saturation and massive liver parenchymal iron accumulation with some Kupffer cell iron loading.…”

Section: Discussionmentioning

confidence: 99%

The molecular basis of ferroportin-linked hemochromatosis

Domenico

Ward

Nemeth

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

206

221

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

The molecular basis of ferroportin-linked hemochromatosis

Domenico

Ward

Nemeth

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

206

221

View full text Add to dashboard Cite

show abstract

“…Characteristics of the study participants are shown in Table 1. In addition, collaborators from several medical centers in The Netherlands provided urine and serum samples from 3 patients with distinct forms of hereditary hemochromatosis not associated with the hemochromatosis (HFE) gene [Online Mendelian Inheritance in Man (OMIM) type 2a, homozygous G320V HJV variation (11 ); OMIM type 4, N144H-caused ferroportin disease (12 )]. Characteristics of these patients are shown in Table 1 in the Data Supplement that accompanies the online version of this article at http://www.…”

Section: Materials and Methods Study Participantsmentioning

confidence: 99%

Mass Spectrometry–Based Hepcidin Measurements in Serum and Urine: Analytical Aspects and Clinical Implications

Kemna

Tjalsma

Podust³

et al. 2007

Clinical Chemistry

204

210

View full text Add to dashboard Cite

Background: Discovery of the central role of hepcidin in body iron regulation has shed new light on the pathophysiology of iron disorders. Information is lacking on newer analytical approaches to measure hepcidin in serum and urine. Recent reports on the measurement of urine and serum hepcidin by surface-enhanced laserdesorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) necessitate analytical and clinical evaluation of MS-based methodologies. Methods: We used SELDI-TOF MS, immunocapture, and tandem MS to identify and characterize hepcidin in serum and urine. In addition to diagnostic application, we investigated analytical reproducibility and biological and preanalytical variation for both serum and urine on Normal Phase 20 and Immobilized Metal Affinity Capture 30 ProteinChip arrays. We obtained samples from healthy controls and patients with documented iron-deficiency anemia, inflammation-induced anemia, thalassemia major, and hereditary hemochromatosis. Results: Proteomic techniques showed that hepcidin-20, -22, and -25 isoforms are present in urine. Hepcidin-25 in serum had the same amino acid sequence as hepcidin-25 in urine, whereas hepcidin-22 was not detected in serum. The interarray CV was 15% to 27%, and interspot CV was 11% to 13%. Preliminary studies showed that hepcidin-25 differentiated disorders of iron metabolism. Urine hepcidin is more affected by multiple freeze-thaw

show abstract

“…In particular, patients with ferroportin variants that completely obstruct hepcidin sensitivity (Y64N and C326S) (122 ) exhibit a more severe phenotype, with predominant iron overload in the hepatocytes. Dysfunction appears to be less severe in patients carrying the N144D and N144H variants, in whom the hepcidin sensitivity of ferroportin is only partially hindered and iron accumulates in both the hepatocytes and macrophages (117,122,131,132 ). Hepcidin concentrations in some of these cases with a gain-of-function phenotype are increased, whereas others are normal but relatively too low to the degree of iron loading (108 ).…”

Section: Hemochromatosis Attributable To Tfr2 Deficiencymentioning

confidence: 99%

Hereditary Hemochromatosis: Genetic Complexity and New Diagnostic Approaches

et al. 2006

View full text Add to dashboard Cite

Since the discovery of the hemochromatosis gene (HFE) in 1996, several novel gene defects have been detected, explaining the mechanism and diversity of iron-overload diseases. At least 4 main types of hereditary hemochromatosis (HH) have been identified. Surprisingly, genes involved in HH encode for proteins that all affect pathways centered around liver hepcidin synthesis and its interaction with ferroportin, an iron exporter in enterocytes and macrophages. Hepcidin concentrations in urine negatively correlate with the severity of HH. Cytokine-mediated increases in hepcidin appear to be an important causative factor in anemia of inflammation, which is characterized by sequestration of iron in the macrophage system. For clinicians, the challenge is now to diagnose HH before irreversible damage develops and, at the same time, to distinguish progressive iron overload from increasingly common diseases with only moderately increased body iron stores, such as the metabolic syndrome. Understanding the molecular regulation of iron homeostasis may be helpful in designing innovative and reliable DNA and protein tests for diagnosis. Subsequently, evidence-based diagnostic strategies must be developed, using both conventional and innovative laboratory tests, to differentiate between the various causes of distortions of iron metabolism. This review describes new insights in mechanisms of iron overload, which are needed to understand new developments in diagnostic medicine.

show abstract

Dominant Hemochromatosis Due to N144H Mutation of SLC11A3: Clinical and Biological Characteristics

Cited by 38 publications

References 13 publications

The molecular basis of ferroportin-linked hemochromatosis

The molecular basis of ferroportin-linked hemochromatosis

Mass Spectrometry–Based Hepcidin Measurements in Serum and Urine: Analytical Aspects and Clinical Implications

Hereditary Hemochromatosis: Genetic Complexity and New Diagnostic Approaches

Contact Info

Product

Resources

About