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{{Hemochromatosis}}
{{Hemochromatosis}}
{{CMG}}
{{CMG}} {{shyam}}; {{AE}}{{SKA}}
 
==Overview==
==Overview==
In patients with high suspicion first test ordered is [[transferrin]] saturation (TS). It is followed by serum ferritin levels. In case of strong evidence of familial history and lab findings, patients should go through genotyping which save the need of unnecessary biopsy of liver to assess the iron index.
==Laboratory Findings==
==Laboratory Findings==
===Electrolyte and Biomarker Studies===
 
'''Serum transferrin saturation'''- A first step is the measurement of [[transferrin]] saturation, the protein which chemically binds to iron and carries it through the blood to the [[liver]], [[spleen]] and [[bone marrow]].<ref>[http://sickle.bwh.harvard.edu/iron_transport.html Transferrin and Iron Transport Physiology]</ref> Measuring transferrin provides a measurement of iron in the blood. Saturation values of 45% are probably a good cutoff to determine whether a patient is a candidate for further testing. <ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=5 Screening and Diagnosis]</ref>  The [[transferrin saturation]] is usually expressed as a percentage, and is calculated as the [[total serum iron]] level divided by the serum iron transferrin level times 100.
===Electrolyte and biomarker studies===
'''Serum ferritin'''- [[Ferritin]], the protein which chemically binds to iron and stores it in the body. Measuring ferritin provides a measurement of iron in the whole body. Normal values for males are 12-300 ng/ml (nanograms per milliliter) and for female, 12-150 ng/ml. Low values indicate [[iron deficiency]], which may be attributed to a number of causes. Higher than normal also may indicate other causes including haemochromatosis.<ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=5 Screening and Diagnosis]</ref><ref>[http://www.nlm.nih.gov/medlineplus/ency/article/003490.htm Ferritin Test] Measuring iron in the body</ref>
'''Serum transferrin saturation''': A first step is the measurement of [[transferrin]] saturation, as transferrin is the protein which chemically binds to iron and carries it through the blood to the [[liver]], [[spleen]] and [[bone marrow]].<ref>[http://sickle.bwh.harvard.edu/iron_transport.html Transferrin and Iron Transport Physiology]</ref> Measuring transferrin provides a measurement of iron in the blood. Saturation values of 45% are probably a good cutoff to determine whether a patient is a candidate for further testing. <ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=5 Screening and Diagnosis]</ref>  The [[transferrin saturation]] is usually expressed as a percentage, and is calculated as the [[total serum iron]] level divided by the serum iron transferrin level times 100.
 
'''Serum ferritin''': [[Ferritin]] is the protein which chemically binds to iron and stores it in the body but does not transport iron. Measuring ferritin provides a measurement of iron in the whole body. Normal values for males are 12-300 ng/ml (nanograms per milliliter) and for female, 12-150 ng/ml. Low values indicate [[iron deficiency]], which may be attributed to a number of causes. Higher than normal also may indicate other causes including hemochromatosis.<ref>[http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=5 Screening and Diagnosis]</ref><ref>[http://www.nlm.nih.gov/medlineplus/ency/article/003490.htm Ferritin Test] Measuring iron in the body</ref>
Other blood tests routinely performed: [[blood count]], [[renal function]], [[liver enzyme]]s, [[electrolyte]]s, [[glucose]] (and/or an [[oral glucose tolerance test]] (OGTT)).
Other blood tests routinely performed: [[blood count]], [[renal function]], [[liver enzyme]]s, [[electrolyte]]s, [[glucose]] (and/or an [[oral glucose tolerance test]] (OGTT)).


'''Blood glucose monitoring''' for patients with hemochromatosis [[diabetes]].
'''Blood glucose monitoring''' for patients with hemochromatosis [[diabetes]].
The following are lab values for diagnosing patient with hemochromatosis:<ref name="pmid21452290">{{cite journal| author=Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS, American Association for the Study of Liver Diseases| title=Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. | journal=Hepatology | year= 2011 | volume= 54 | issue= 1 | pages= 328-43 | pmid=21452290 | doi=10.1002/hep.24330 | pmc=3149125 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21452290  }}</ref>
{| class="wikitable"
!Measurements
!Asymptomatic
!Symptomatic
|-
|Serum iron level (μg/dL)
|150-280
|180-300
|-
|Serum transferrin saturation
|45-100
|80-100
|-
| rowspan="2" |Serum ferritin level (μg/L)
|Men 150-1000
|500-6000
|-
|Female 120-1000
|500-6000
|-
|Hepatic iron concentration μg/g dry weight
|2000-10,000
|8000-30,000
|-
|Perls' Prussian blue stain
|2+ to 4+
|3+, 4+
|-
|Hepatic iron index
|>1.9
|>1.9
|}
====Screening and diagnosis of hemochromatosis.WT, wild type; HII, histologic iron index; CII, chemical iron index; HH, hereditary hemochromatosis<ref name="pmid22675794">{{cite journal| author=Bacon BR| title=Hemochromatosis: discovery of the HFE gene. | journal=Mo Med | year= 2012 | volume= 109 | issue= 2 | pages= 133-6 | pmid=22675794 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22675794  }}</ref><ref name="pmid20492323">{{cite journal| author=Asia-Pacific Working Party on Prevention of Hepatocellular Carcinoma| title=Prevention of hepatocellular carcinoma in the Asia-Pacific region: consensus statements. | journal=J Gastroenterol Hepatol | year= 2010 | volume= 25 | issue= 4 | pages= 657-63 | pmid=20492323 | doi=10.1111/j.1440-1746.2009.06167.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20492323  }}</ref><ref name="pmid25976957">{{cite journal| author=Adams PC| title=Epidemiology and diagnostic testing for hemochromatosis and iron overload. | journal=Int J Lab Hematol | year= 2015 | volume= 37 Suppl 1 | issue=  | pages= 25-30 | pmid=25976957 | doi=10.1111/ijlh.12347 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25976957  }}</ref><ref name="pmid25454304">{{cite journal| author=Salgia RJ, Brown K| title=Diagnosis and management of hereditary hemochromatosis. | journal=Clin Liver Dis | year= 2015 | volume= 19 | issue= 1 | pages= 187-98 | pmid=25454304 | doi=10.1016/j.cld.2014.09.011 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25454304  }}</ref><ref name="pmid23418762">{{cite journal| author=Crownover BK, Covey CJ| title=Hereditary hemochromatosis. | journal=Am Fam Physician | year= 2013 | volume= 87 | issue= 3 | pages= 183-90 | pmid=23418762 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23418762  }}</ref><ref name="pmid25864215">{{cite journal| author=Adams PC, Barton JC, Guo H, Alter D, Speechley M| title=Serum ferritin is a biomarker for liver mortality in the Hemochromatosis and Iron Overload Screening Study. | journal=Ann Hepatol | year= 2015 | volume= 14 | issue= 3 | pages= 348-53 | pmid=25864215 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25864215  }}</ref><ref name="pmid23862168">{{cite journal| author=Adams PC, McLaren CE, Speechley M, McLaren GD, Barton JC, Eckfeldt JH| title=HFE mutations in Caucasian participants of the Hemochromatosis and Iron Overload Screening study with serum ferritin level <1000 µg/L. | journal=Can J Gastroenterol | year= 2013 | volume= 27 | issue= 7 | pages= 390-2 | pmid=23862168 | doi= | pmc=3956024 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23862168  }}</ref><ref name="pmid25314357">{{cite journal| author=Lim A, Speechley M, Adams PC| title=Predicting C282Y homozygote genotype for hemochromatosis using serum ferritin and transferrin saturation values from 44,809 participants of the HEIRS study. | journal=Can J Gastroenterol Hepatol | year= 2014 | volume= 28 | issue= 9 | pages= 502-4 | pmid=25314357 | doi= | pmc=4205907 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25314357  }}</ref>====
{{familytree/start|summary=Algorithm for screening and diagnosis of hemochromatosis.WT, wild type; HII, histologic iron index; CII, chemical iron index; HH, hereditary hemochromatosis.}}
{{familytree| | | | | | | | | | | | |A01| | | | | | | | | |A01=Serum Transferrin Saturation<br>TS}}
{{familytree| | | | | | | | | |,|-|-|-|^|-|-|-|.| | | | | | |}}
{{familytree| | | | | | | | | |!| | | | | | | |!| | | | | |}}
{{familytree| | | | | | | | |B01| | | | | |B02| | | | |B01=<50% premenopausal females<br><60% men, postmenopausal women|B02=≥50% premenopausal females<br>≥60% men, postmenopausal women}}
{{familytree| | | | | | | | | |!| | | | | | | |!| | | | |}}
{{familytree| | | | | | | | | |!| | | | | | |Q01| | | | |Q01=1 Repeat Transferrin Saturation TS<br>2 Serum Ferritin SF}}
{{familytree| | | | | | | | | |!| | |,|-|-|-|-|^|-|-|.| |}}
{{familytree| | | | | | | | |C01| |!| | | | | | | |!| | |C01=Repeat testing every 5 year}}
{{familytree| | | | | | | | |,|-|-|-|'| | | | | | | |!| | |}}
{{familytree| | | | | | | | |!| | | | | | | | | | | |!| |}}
{{familytree| | | | | | | | |D01| | | | | | | | |D02| |D01=TS:<50% premenopausal females<br>TS: <60% men, postmenopausal women<br>SF: 20-250μg/L menopausal females<br>SF: 10-120μg/L men, menopausal women|D02=TS:≥50% premenopausal females<br>TS: ≥60% men, postmenopausal women<br>SF:>200 μg/L premenopausal females<br>SF:>300 μg/L men, menopausal women}}
{{familytree| | | | | | | | | |!| | | | | | |,|-|-|-|^|-|-|-|-|.|}}
{{familytree| | | | | | | | |E01| | | | |E02| | | | | | |E03|E01=Repeat TS and SF every 2-3 year|E02=Serum Ferritin<1000 μg/L|E03=Serum Ferritin>1000 μg/L}}
{{familytree| | | | | | | | | | | | | | | | |!|,|-|-|-|-|-|-|^|-|-|.|}}
{{familytree| | | | | | | | | | | | | | | |F01| | | | | | | | |F02|F01=Geno-typing|F02=Liver biopsy}}
{{familytree| | | | | | | | |,|-|-|v|-|-|-|^|-|-|v|-|-|.| | | | |,|-|^|-|.| |}}
{{familytree| | | | | | | |G01| |G02| | | |G03| |G04| | |G05| |G06|G01=WT/WT genotype|G02=C282Y/WT genotype|G03=C282Y/H63D genotype|G04=C282Y/C282Y genotype|G05=Histological iron index<0.15<br>Chemical iron index<2.0|G06=Histological iron index>0.15<br>Chemical iron index>2.0}}
{{familytree| | | | | | | | |`|-|V|-|'| | | | | |`|-|V|-|'| | | | |!| | |!|}}
{{familytree| | | | | | | | | |H01| | | | | | | |H02| | | | |H03| |H04|H01=Secondary hemochromatosis|H02=Phelebotomy to maintain Serum Feretin|H03=Repeat TS and SF after 2-3 year|H04=Phelebotomy to maintain Serum Feretin}}
{{familytree| | | | | | | | | | |!| | | | | | | | | |!| | |}}
{{familytree| | | | | | | | | |K01| | | | | | | |K02|K01=Screen family with Transferrin Saturation & Serum Ferritin if atypical HH suspected|K02=Screen family with genotyping}}
{{familytree| | | | | | | | | | | | | | | | | | | | |!| |}}
{{familytree| | | | | | | | | | | | | | | | | | | |J01|J01=Moniter Transferin Saturation & Serum Feretin in subclinical members}}
{{familytree/end}}


==References==
==References==
{{reflist|2}}
{{reflist|2}}
[[Category:Gastroenterology]]
[[Category:Cardiology]]
[[Category:Hepatology]]
[[Category:Endocrinology]]
[[Category:Hematology]]
[[Category:Disease]]
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<references />

Latest revision as of 18:18, 1 January 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]; Associate Editor(s)-in-Chief: Sunny Kumar MD [3]

Overview

In patients with high suspicion first test ordered is transferrin saturation (TS). It is followed by serum ferritin levels. In case of strong evidence of familial history and lab findings, patients should go through genotyping which save the need of unnecessary biopsy of liver to assess the iron index.

Laboratory Findings

Electrolyte and biomarker studies

Serum transferrin saturation: A first step is the measurement of transferrin saturation, as transferrin is the protein which chemically binds to iron and carries it through the blood to the liver, spleen and bone marrow.[1] Measuring transferrin provides a measurement of iron in the blood. Saturation values of 45% are probably a good cutoff to determine whether a patient is a candidate for further testing. [2] The transferrin saturation is usually expressed as a percentage, and is calculated as the total serum iron level divided by the serum iron transferrin level times 100.

Serum ferritin: Ferritin is the protein which chemically binds to iron and stores it in the body but does not transport iron. Measuring ferritin provides a measurement of iron in the whole body. Normal values for males are 12-300 ng/ml (nanograms per milliliter) and for female, 12-150 ng/ml. Low values indicate iron deficiency, which may be attributed to a number of causes. Higher than normal also may indicate other causes including hemochromatosis.[3][4] Other blood tests routinely performed: blood count, renal function, liver enzymes, electrolytes, glucose (and/or an oral glucose tolerance test (OGTT)).

Blood glucose monitoring for patients with hemochromatosis diabetes.

The following are lab values for diagnosing patient with hemochromatosis:[5]

Measurements Asymptomatic Symptomatic
Serum iron level (μg/dL) 150-280 180-300
Serum transferrin saturation 45-100 80-100
Serum ferritin level (μg/L) Men 150-1000 500-6000
Female 120-1000 500-6000
Hepatic iron concentration μg/g dry weight 2000-10,000 8000-30,000
Perls' Prussian blue stain 2+ to 4+ 3+, 4+
Hepatic iron index >1.9 >1.9

Screening and diagnosis of hemochromatosis.WT, wild type; HII, histologic iron index; CII, chemical iron index; HH, hereditary hemochromatosis[6][7][8][9][10][11][12][13]

 
 
 
 
 
 
 
 
 
 
 
 
Serum Transferrin Saturation
TS
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
<50% premenopausal females
<60% men, postmenopausal women
 
 
 
 
 
≥50% premenopausal females
≥60% men, postmenopausal women
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Repeat Transferrin Saturation TS
2 Serum Ferritin SF
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat testing every 5 year
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TS:<50% premenopausal females
TS: <60% men, postmenopausal women
SF: 20-250μg/L menopausal females
SF: 10-120μg/L men, menopausal women
 
 
 
 
 
 
 
 
TS:≥50% premenopausal females
TS: ≥60% men, postmenopausal women
SF:>200 μg/L premenopausal females
SF:>300 μg/L men, menopausal women
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat TS and SF every 2-3 year
 
 
 
 
Serum Ferritin<1000 μg/L
 
 
 
 
 
 
Serum Ferritin>1000 μg/L
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Geno-typing
 
 
 
 
 
 
 
 
Liver biopsy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WT/WT genotype
 
C282Y/WT genotype
 
 
 
C282Y/H63D genotype
 
C282Y/C282Y genotype
 
 
Histological iron index<0.15
Chemical iron index<2.0
 
Histological iron index>0.15
Chemical iron index>2.0
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Secondary hemochromatosis
 
 
 
 
 
 
 
Phelebotomy to maintain Serum Feretin
 
 
 
 
Repeat TS and SF after 2-3 year
 
Phelebotomy to maintain Serum Feretin
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screen family with Transferrin Saturation & Serum Ferritin if atypical HH suspected
 
 
 
 
 
 
 
Screen family with genotyping
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moniter Transferin Saturation & Serum Feretin in subclinical members

References

  1. Transferrin and Iron Transport Physiology
  2. Screening and Diagnosis
  3. Screening and Diagnosis
  4. Ferritin Test Measuring iron in the body
  5. Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS, American Association for the Study of Liver Diseases (2011). "Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases". Hepatology. 54 (1): 328–43. doi:10.1002/hep.24330. PMC 3149125. PMID 21452290.
  6. Bacon BR (2012). "Hemochromatosis: discovery of the HFE gene". Mo Med. 109 (2): 133–6. PMID 22675794.
  7. Asia-Pacific Working Party on Prevention of Hepatocellular Carcinoma (2010). "Prevention of hepatocellular carcinoma in the Asia-Pacific region: consensus statements". J Gastroenterol Hepatol. 25 (4): 657–63. doi:10.1111/j.1440-1746.2009.06167.x. PMID 20492323.
  8. Adams PC (2015). "Epidemiology and diagnostic testing for hemochromatosis and iron overload". Int J Lab Hematol. 37 Suppl 1: 25–30. doi:10.1111/ijlh.12347. PMID 25976957.
  9. Salgia RJ, Brown K (2015). "Diagnosis and management of hereditary hemochromatosis". Clin Liver Dis. 19 (1): 187–98. doi:10.1016/j.cld.2014.09.011. PMID 25454304.
  10. Crownover BK, Covey CJ (2013). "Hereditary hemochromatosis". Am Fam Physician. 87 (3): 183–90. PMID 23418762.
  11. Adams PC, Barton JC, Guo H, Alter D, Speechley M (2015). "Serum ferritin is a biomarker for liver mortality in the Hemochromatosis and Iron Overload Screening Study". Ann Hepatol. 14 (3): 348–53. PMID 25864215.
  12. Adams PC, McLaren CE, Speechley M, McLaren GD, Barton JC, Eckfeldt JH (2013). "HFE mutations in Caucasian participants of the Hemochromatosis and Iron Overload Screening study with serum ferritin level <1000 µg/L". Can J Gastroenterol. 27 (7): 390–2. PMC 3956024. PMID 23862168.
  13. Lim A, Speechley M, Adams PC (2014). "Predicting C282Y homozygote genotype for hemochromatosis using serum ferritin and transferrin saturation values from 44,809 participants of the HEIRS study". Can J Gastroenterol Hepatol. 28 (9): 502–4. PMC 4205907. PMID 25314357.

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