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African iron overload

African iron overload
Classification and external resources
OMIM 601195
DiseasesDB 35029
MeSH C537904

African iron overload, also known as (Bantu siderosis,or Dietary iron overload), is an iron overload disorder first observed among people of African descent in Southern Africa and Central Africa.[1] Dietary iron overload is the consumption of large amount of home-brewed beer with high amount of iron content in it. Preparing beer in iron pots or drums results in high iron content. The iron content in home-brewed beer is around 46–82 mg/l compared to 0.5 mg/l in commercial beer.[1][2] Dietary overload was prevalent in both the rural and urban Black African population, with the introduction of commercial beer in urban areas, the condition has virtually decreased. However, the condition is still common in rural areas.[1] Until recently, studies have shown that genetics might play a role in this disorder. Combination of excess iron and functional changes in ferroportin seems to be the probable cause.[3][4] This disorder can be treated with phlebotomy therapy or (iron-chelation) therapy.

Contents

  • Mechanism 1
    • SLC40A1 gene association to African iron overload 1.1
    • African Dietary iron overload as a cause of hepatocellular carcinoma 1.2
  • Symptoms 2
  • Diagnosis 3
  • Treatment 4
  • Prognosis 5
  • Recent research 6
  • References 7
  • External links 8

Mechanism

Originally, this was blamed on ungalvanised barrels used to store home-made beer, which led to increased oxidation and increased iron levels in the beer. Further investigation has shown that only some people drinking this sort of beer get an iron overload syndrome, and that a similar syndrome occurred in people of African descent who have had no contact with this kind of beer (e.g., African Americans).[5]

This led investigators to the discovery of a gene polymorphism in the gene for ferroportin, which predisposes some people of African descent to iron overload.[6]

SLC40A1 gene association to African iron overload

SLC40A1 gene encodes for ferroportin. It is the main iron export protein. A mutation in SLC40A1 was detected in minority of African American and Native African with primary iron overload,[6][7] but the ferroportin (Q248H) mutation was not found more regularly in Native southern Africans with dietary iron overload.[8]

Polymorphisms in SLC40A1 have recently been investigated in Americans of African descent.[3] Ferroportin SLC40A1 Q248H mutation in exon 6 occurs as a polymorphism in individuals of sub-Saharan African descent,[6][7][9] but it was not identified in western Caucasians.[6] Q248H mutation appears to be unique to African populations. Moreover, studies have shown that SLC40A1 Q248H aggregate allele frequency is higher in Native Africans than the aggregate allele frequency in African Americans.[3]

Ferroportin Q248H mutation in African families with dietary iron overload showed lower mean cell volume and higher ferritin concentration. It is suggested that the mutation might interfere with iron supply.[8]

The probable cause of African iron overload is the combination of excess iron intake and functional changes in ferroportin.[3][4] Penetrance of Q248H as a cause of iron overload is most likely low.[3][8]

African Dietary iron overload as a cause of hepatocellular carcinoma

Excess hepatic iron in dietary iron overload is typically associated with serum ferritin saturation of greater than 700pg/l and transferrin saturation of greater than 55%.[10]

Increased

External links

  1. ^ a b c d Kew, MC; Asare, GA (Aug 2007). "Dietary iron overload in the African and hepatocellular carcinoma.". Liver international : official journal of the International Association for the Study of the Liver 27 (6): 735–41.  
  2. ^ a b c MacPhail, AP; Mandishona, EM; Bloom, PD; Paterson, AC; Rouault, TA; Gordeuk, VR (Sep 1999). "Measurements of iron status and survival in African iron overload.". South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 89 (9): 966–72.  
  3. ^ a b c d e Barton JC, Acton RT, Lee PL, West C (2007). "SLC40A1 Q248H allele frequencies and Q248H-associated risk of non-HFE iron overload in persons of sub-Saharan African descent". Blood Cells Mol. Dis. 39 (2): 206–11.  
  4. ^ a b c d e Fleming, RE; Ponka, P (Jan 26, 2012). "Iron overload in human disease.". The New England Journal of Medicine 366 (4): 348–59.  
  5. ^ Gordeuk V, Mukiibi J, Hasstedt SJ et al. (January 1992). "Iron overload in Africa. Interaction between a gene and dietary iron content".  
  6. ^ a b c d Gordeuk VR, Caleffi A, Corradini E et al. (2003). "Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene". Blood Cells Mol. Dis. 31 (3): 299–304.  
  7. ^ a b Beutler, E; Barton, JC; Felitti, VJ; Gelbart, T; West, C; Lee, PL; Waalen, J; Vulpe, C (Nov–Dec 2003). "Ferroportin 1 (SCL40A1) variant associated with iron overload in African-Americans.". Blood cells, molecules & diseases 31 (3): 305–9.  
  8. ^ a b c d McNamara, L; Gordeuk, VR; MacPhail, AP (Dec 2005). "Ferroportin (Q248H) mutations in African families with dietary iron overload.". Journal of Gastroenterology and Hepatology 20 (12): 1855–8.  
  9. ^ a b Barton, JC; Acton, RT; Rivers, CA; Bertoli, LF; Gelbart, T; West, C; Beutler, E (Nov–Dec 2003). "Genotypic and phenotypic heterogeneity of African Americans with primary iron overload.". Blood cells, molecules & diseases 31 (3): 310–9.  
  10. ^ Moyo, VM; Gangaidzo, IT; Gomo, ZA; Khumalo, H; Saungweme, T; Kiire, CF; Rouault, T; Gordeuk, VR (Mar 15, 1997). "Traditional beer consumption and the iron status of spouse pairs from a rural community in Zimbabwe.". Blood 89 (6): 2159–66.  
  11. ^ Hagen, TM; Huang, S; Curnutte, J; Fowler, P; Martinez, V; Wehr, CM; Ames, BN; Chisari, FV (Dec 20, 1994). "Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma.". Proceedings of the National Academy of Sciences of the United States of America 91 (26): 12808–12.  
  12. ^ Jüngst, C; Cheng, B; Gehrke, R; Schmitz, V; Nischalke, HD; Ramakers, J; Schramel, P; Schirmacher, P; Sauerbruch, T; Caselmann, WH (Jun 2004). "Oxidative damage is increased in human liver tissue adjacent to hepatocellular carcinoma.". Hepatology (Baltimore, Md.) 39 (6): 1663–72.  
  13. ^ Asare, GA; Mossanda, KS; Kew, MC; Paterson, AC; Kahler-Venter, CP; Siziba, K (Feb 15, 2006). "Hepatocellular carcinoma caused by iron overload: a possible mechanism of direct hepatocarcinogenicity.". Toxicology 219 (1-3): 41–52.  
  14. ^ Thirunavukkarasu, C; Sakthisekaran, D (Mar 2001). "Effect of selenium on N-nitrosodiethylamine-induced multistage hepatocarcinogenesis with reference to lipid peroxidation and enzymic antioxidants.". Cell biochemistry and function 19 (1): 27–35.  
  15. ^ "African Iron Overload". National Organization of Rare Disorder. Retrieved 9 April 2014. 
  16. ^ a b c d Knovich, MA; Storey, JA; Coffman, LG; Torti, SV; Torti, FM (May 2009). "Ferritin for the clinician.". Blood reviews 23 (3): 95–104.  
  17. ^ a b "Ferritin". MedlinePlus. Retrieved 9 April 2014. 
  18. ^ a b "Iron (Fe)". Web MD. Retrieved 9 April 2014. 
  19. ^ McLaren, CE; Barton, JC; Adams, PC; Harris, EL; Acton, RT; Press, N; Reboussin, DM; McLaren, GD; Sholinsky, P; Walker, AP; Gordeuk, VR; Leiendecker-Foster, C; Dawkins, FW; Eckfeldt, JH; Mellen, BG; Speechley, M; Thomson, E; Hemochromatosis and Iron Overload Study Research, Investigators (Feb 2003). "Hemochromatosis and Iron Overload Screening (HEIRS) study design for an evaluation of 100,000 primary care-based adults.". The American journal of the medical sciences 325 (2): 53–62.  
  20. ^ a b "Vitamin-C". GlobalRPH. Retrieved 9 April 2014. 
  21. ^ a b c d "Gamma-glutamyl transpeptidase". Medizinsch-Diagnostische Institute. Retrieved 9 April 2014. 
  22. ^ "African Hemochromatosis". Iron Disorders Institute. Retrieved 17 April 2014. 
  23. ^ McGregor, JA; Shayeghi, M; Vulpe, CD; Anderson, GJ; Pietrangelo, A; Simpson, RJ; McKie, AT (Jul 2005). "Impaired iron transport activity of ferroportin 1 in hereditary iron overload.". The Journal of membrane biology 206 (1): 3–7.  
  24. ^ a b Drakesmith, H; Schimanski, LM; Ormerod, E; Merryweather-Clarke, AT; Viprakasit, V; Edwards, JP; Sweetland, E; Bastin, JM; Cowley, D; Chinthammitr, Y; Robson, KJ; Townsend, AR (Aug 1, 2005). "Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin.". Blood 106 (3): 1092–7.  
  25. ^ Schimanski, LM; Drakesmith, H; Merryweather-Clarke, AT; Viprakasit, V; Edwards, JP; Sweetland, E; Bastin, JM; Cowley, D; Chinthammitr, Y; Robson, KJ; Townsend, AR (May 15, 2005). "In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations.". Blood 105 (10): 4096–102.  

References

Distinctive phenotypes of individuals with SLC40A1 Q248H are minor, if any. Serum ferritin concentration is likely to be high in persons with Q248H (mostly heterozygotes) than in wild-type SLC40A1.[9] In xenopus oocytes and HEK 293 cells, the expression of wild type ferroportin was similar to the expression of ferroportin Q248H at the plasma membrane.[23] In HEK 293 cells, Q248H was as predisposed to the activities of hepcidin-25 as wild type ferroportin.[24] Ferroportin Q248H also unregulated the expression of transferrin receptor-1 in the same way as wild type. This indicates the ferroportin Q248H is associated with mild clinical phenotype or causes iron disorder in the presence of other factors.[24][25]

Recent research

Individuals of sub-Saharan African descent with ferroportin Q248H are more likely to be diagnosed with African iron overload than individual without ferroportin mutation because individuals with ferroportin Q248H have elevated level of serum ferritin concentration.[8] Individuals of African descent should also avoid drinking traditional beer.

Prognosis

A person's hemoglobin is important in the physician's consideration of iron reduction therapy. A physician can provide therapeutic phlebotomy if the patient's hemoglobin level is sufficient enough to sustain blood removal. The physician can also recommend the patient to routinely donate blood. When a patient's hemoglobin is not sufficient for phlebotomy. Iron reduction will likely require the removal of iron using specific drugs (iron-chelation). The physician may use a combination of these therapies in some situations.[22]

Treatment

It is important to use both the imaging techniques and serum ferritin level as indicators to start the therapy of iron overload. Serum level and the imaging techniques can be used as markers for treatment progress.

[16] [16] The severity of iron overload can be determined and monitored using a combination of tests. Measurement of serum ferritin indicates for total body iron overload.

Measurement of iron-related features
Characteristic Normal range Unit
Vitamin C 0.2 - 2[20]
11 - 114[20]
mg/dL
µmol/L
Gamma-glutamyl transpeptidase in male < 55.2[21]
0.92[21]
U/l
μkat/l
Gamma-glutamyl transpeptidase in female < 37.8[21]
0.63[21]
U/l
μkat/l

Chemical evidence of tissue vitamin C deficiency and mild to moderate liver dysfunction are likely to be seen in individuals with African iron overload.[2] Elevation in Gamma-glutamyl transpeptidase can be used as a marker for abnormalities in liver function.

Ferritin level above 200 ng/mL (449 pmol/L) in women or 300 ng/mL (674 pmol/L) in men who have no signs of inflammatory disease need additional testing. Transferrin saturation above normal range in male and female also need additional testing.[19]

Measurement of iron status
Characteristic Normal range Unit
Ferritin-male 12 - 300[17] ng/mL
Ferritin-female 12 - 150[17] ng/mL
Transferrin saturation-male 10 - 50[18] %
Transferrin saturation-female 15 - 50[18] %

Elevation in ferritin concentration without elevation in transferrin saturation does not rule out an iron overload disorder. This combination can be observed in loss-of-function ferroportin mutation and in aceruloplasminemia.[4] Elevated level of ferritin concentration can be observed in acute or chronic inflammatory process without pathologic iron overload.[16]

Diagnosis

Symptoms can vary from one person to another. It depends on the extent of accumulation and on the body location of the accumulation. African iron overload can be considered in patient with some of these conditions.[2][15]

Symptoms

[1]

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