Difference between revisions of "Hereditary hemochromatosis"

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#redirect [[Medical_liver_disease#Hereditary_hemochromatosis]]
'''Hereditary hemochromatosis''', abbreviated '''HH''', is a genetic (autosomal dominant inherited) cause of iron deposition.


Secondary causes of hemochromatosis are dealt with in ''[[secondary hemochromatosis]]''.
==General==
Epidemiology:
*Genetic defect - ''HFE gene''.<ref name=omim613609>{{OMIM|613609}}</ref>
**One mutation (C282Y mutation) in up to 12.5% of people in populations of northern and central European origin.<ref name=pmid18192769>{{cite journal |author=Weinberg ED |title=Survival advantage of the hemochromatosis C282Y mutation |journal=Perspect. Biol. Med. |volume=51 |issue=1 |pages=98-102 |year=2008 |pmid=18192769 |doi=10.1353/pbm.2008.0001 |url=}}</ref>
**Homozygotes get the disease.<ref name=omim613609>{{OMIM|613609}}</ref>
*Onset in males earlier than females (due to menses).
*Mutation thought to confer survival advantage - several theories (increased resistance to [[TB]], S. typhi vs. decreased iron deficiency/increased iron absorption).<ref name=pmid18192769/>
Associated pathology (mnemonic: '''h'''emochromatosis '''c'''an '''c'''ause '''d'''eposits '''a'''nywhere''):<ref>URL: [http://en.wikibooks.org/wiki/USMLE_Step_2_Review http://en.wikibooks.org/wiki/USMLE_Step_2_Review]. Accessed on: 15 March 2012.</ref><ref name=pmid19034258>{{Cite journal  | last1 = Fix | first1 = OK. | last2 = Kowdley | first2 = KV. | title = Hereditary hemochromatosis. | journal = Minerva Med | volume = 99 | issue = 6 | pages = 605-17 | month = Dec | year = 2008 | doi =  | PMID = 19034258 }}</ref>
*Hypogonadism.
*[[Cirrhosis]] and [[HCC]].
*[[Cardiomyopathy]] - [[DCM]] (esp. with ''his63asp'' mutation),<ref name=pmid11040018>{{Cite journal  | last1 = Mahon | first1 = NG. | last2 = Coonar | first2 = AS. | last3 = Jeffery | first3 = S. | last4 = Coccolo | first4 = F. | last5 = Akiyu | first5 = J. | last6 = Zal | first6 = B. | last7 = Houlston | first7 = R. | last8 = Levin | first8 = GE. | last9 = Baboonian | first9 = C. | title = Haemochromatosis gene mutations in idiopathic dilated cardiomyopathy. | journal = Heart | volume = 84 | issue = 5 | pages = 541-7 | month = Nov | year = 2000 | doi =  | PMID = 11040018 }}</ref> may be [[RCM]].
*[[Diabetes mellitus]] (bronze diabetes).
*Arthropathy.<ref name=pmid11148720>{{Cite journal  | last1 = von Kempis | first1 = J. | title = Arthropathy in hereditary hemochromatosis. | journal = Curr Opin Rheumatol | volume = 13 | issue = 1 | pages = 80-3 | month = Jan | year = 2001 | doi =  | PMID = 11148720 }}</ref>
Pathophysiology:
*Iron overload -> [[cirrhosis]].
==Microscopic==
Features:
*Periportal iron deposition (early).
**Late stage disease has diffuse iron deposition.
*Brown granular - may vaguely look like [[lipofuscin]] on [[H&E]].
Notes:
*Iron in the bile ducts and endothelium used to be though specific of hereditary hemochromatosis.<ref>MG. 17 September 2009.</ref>
**It is now thought to just reflect the severity of iron deposition, i.e. if the bile ducts and endothelium have iron - it is severe.
DDx - secondary hemochromatosis:
*[[Myelodysplastic syndrome]].
*Chronic hemolysis.
*Alcoholic liver disease; iron deposition common in [[cirrhosis]].
===Images===
<gallery>
Image:Hemosiderosis_high_mag.jpg | Hemosiderosis - iron stain. (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case77/path.html Hemochromatosis (upmc.edu)].
{|
[[File:1 Iron 1 680x512px.tif|Trichrome shows thin fibrous bands (20X).]]
[[File:2 Iron 1 680x512px.tif|Iron stain shows dense iron deposition (40X).]]
|-
[[File:3 Iron 1 680x512px.tif|At high power, a modest inflammatory infiltrate accompanies proliferating bile ductules; no piecemeal necrosis (400X)]]
[[File:4 Iron 1 1360x1024px.tif|Reticulin stain with regenerative findings, cords with two nuclei thickness, hepatic acini (400X, higher pixel photo)]]
|}
Hemochromatosis with bridging fibrosis.
Trichrome shows thin fibrous bands (Row 1 Left 20X). Iron stain shows dense iron deposition (Row 1 Right 40X). At high power, a modest inflammatory infiltrate accompanies proliferating bile ductules; no piecemeal necrosis (Row 2 Left 400X). Reticulin stain with regenerative findings, cords with two nuclei thickness, hepatic acini (Row 2 right 400X, higher pixel photo).
{|
[[File:1 Iron 2 680x512px.tif|Fibrous bands dissect hepatocyte nodules (Row 1 Left 20X).]]
[[File:2 Iron 2 680x512px.tif|Iron stain shows 4+ iron, identifiable at the lowest magnification, as well by naked eye (Row 1 Right 20X)]]
<br>
[[File:3 Iron 2 680x512px.tif|This nodule has occasionally enlarged nuclei, which should not be considered dysplasia in and of itself. Note associated relatively inflammation free band with proliferated bile ductules. (Row 2 Left 400X).]]
[[File:4 Iron 2 680x512px.tif|Reticulin stain shows two cell thick regenerative cords with sinusoidal black lines lacking orientation (Row 2 Right 400X).]]
|}
Hemochromatosis with cirrhosis..
Fibrous bands dissect hepatocyte nodules (Row 1 Left 20X). Iron stain shows 4+ iron, identifiable at the lowest magnification, as well by naked eye (Row 1 Right 20X) This nodule has occasionally enlarged nuclei, which should not be considered dysplasia in and of itself. Note associated relatively inflammation free band with proliferated bile ductules. (Row 2 Left 400X). Reticulin stain shows two cell thick regenerative cords with sinusoidal black lines lacking orientation (Row 2 Right 400X).
==Stains==
Iron stain +ve -- '''important'''.
*Light blue haze is not enough.
**Must be separated from ''siderosis'' -- iron in Kupffer cells.
===Grading===
The quantity of iron is scored as follows:
*0 = none.
*1: only at high power.
*2: at medium power.
*3: at lowest power.
*4: seen without microscope.
==Molecular==
*PCR - '''diagnostic''' - see ''[[molecular pathology tests]]''.
==See also==
*[[Medical liver disease]].
==References==
{{Reflist|2}}
[[Category:Diagnosis]]
[[Category:Diagnosis]]
[[Category:Medical liver disease]]

Latest revision as of 14:35, 29 August 2016

Hereditary hemochromatosis, abbreviated HH, is a genetic (autosomal dominant inherited) cause of iron deposition.

Secondary causes of hemochromatosis are dealt with in secondary hemochromatosis.

General

Epidemiology:

  • Genetic defect - HFE gene.[1]
    • One mutation (C282Y mutation) in up to 12.5% of people in populations of northern and central European origin.[2]
    • Homozygotes get the disease.[1]
  • Onset in males earlier than females (due to menses).
  • Mutation thought to confer survival advantage - several theories (increased resistance to TB, S. typhi vs. decreased iron deficiency/increased iron absorption).[2]

Associated pathology (mnemonic: hemochromatosis can cause deposits anywhere):[3][4]

Pathophysiology:

Microscopic

Features:

  • Periportal iron deposition (early).
    • Late stage disease has diffuse iron deposition.
  • Brown granular - may vaguely look like lipofuscin on H&E.

Notes:

  • Iron in the bile ducts and endothelium used to be though specific of hereditary hemochromatosis.[7]
    • It is now thought to just reflect the severity of iron deposition, i.e. if the bile ducts and endothelium have iron - it is severe.

DDx - secondary hemochromatosis:

Images

  • Hemosiderosis - iron stain. (WC)

www:

Trichrome shows thin fibrous bands (20X).Iron stain shows dense iron deposition (40X).At high power, a modest inflammatory infiltrate accompanies proliferating bile ductules; no piecemeal necrosis (400X)Reticulin stain with regenerative findings, cords with two nuclei thickness, hepatic acini (400X, higher pixel photo)

Hemochromatosis with bridging fibrosis. Trichrome shows thin fibrous bands (Row 1 Left 20X). Iron stain shows dense iron deposition (Row 1 Right 40X). At high power, a modest inflammatory infiltrate accompanies proliferating bile ductules; no piecemeal necrosis (Row 2 Left 400X). Reticulin stain with regenerative findings, cords with two nuclei thickness, hepatic acini (Row 2 right 400X, higher pixel photo).

Fibrous bands dissect hepatocyte nodules (Row 1 Left 20X).Iron stain shows 4+ iron, identifiable at the lowest magnification, as well by naked eye (Row 1 Right 20X)
This nodule has occasionally enlarged nuclei, which should not be considered dysplasia in and of itself. Note associated relatively inflammation free band with proliferated bile ductules. (Row 2 Left 400X).Reticulin stain shows two cell thick regenerative cords with sinusoidal black lines lacking orientation (Row 2 Right 400X).

Hemochromatosis with cirrhosis.. Fibrous bands dissect hepatocyte nodules (Row 1 Left 20X). Iron stain shows 4+ iron, identifiable at the lowest magnification, as well by naked eye (Row 1 Right 20X) This nodule has occasionally enlarged nuclei, which should not be considered dysplasia in and of itself. Note associated relatively inflammation free band with proliferated bile ductules. (Row 2 Left 400X). Reticulin stain shows two cell thick regenerative cords with sinusoidal black lines lacking orientation (Row 2 Right 400X).

Stains

Iron stain +ve -- important.

  • Light blue haze is not enough.
    • Must be separated from siderosis -- iron in Kupffer cells.

Grading

The quantity of iron is scored as follows:

  • 0 = none.
  • 1: only at high power.
  • 2: at medium power.
  • 3: at lowest power.
  • 4: seen without microscope.

Molecular

See also

References

  1. ↑ 1.0 1.1 Online 'Mendelian Inheritance in Man' (OMIM) 613609
  2. ↑ 2.0 2.1 Weinberg ED (2008). "Survival advantage of the hemochromatosis C282Y mutation". Perspect. Biol. Med. 51 (1): 98-102. doi:10.1353/pbm.2008.0001. PMID 18192769.
  3. ↑ URL: http://en.wikibooks.org/wiki/USMLE_Step_2_Review. Accessed on: 15 March 2012.
  4. ↑ Fix, OK.; Kowdley, KV. (Dec 2008). "Hereditary hemochromatosis.". Minerva Med 99 (6): 605-17. PMID 19034258.
  5. ↑ Mahon, NG.; Coonar, AS.; Jeffery, S.; Coccolo, F.; Akiyu, J.; Zal, B.; Houlston, R.; Levin, GE. et al. (Nov 2000). "Haemochromatosis gene mutations in idiopathic dilated cardiomyopathy.". Heart 84 (5): 541-7. PMID 11040018.
  6. ↑ von Kempis, J. (Jan 2001). "Arthropathy in hereditary hemochromatosis.". Curr Opin Rheumatol 13 (1): 80-3. PMID 11148720.
  7. ↑ MG. 17 September 2009.
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