Editing Hereditary haemochromatosis (section)

== Signs and symptoms ==
Haemochromatosis is [[wikt:protean|protean]] in its manifestations, ''i.e.'', often presenting with signs or symptoms suggestive of other diagnoses that affect specific organ systems. Many of the signs and symptoms below are uncommon, and most patients with the hereditary form of haemochromatosis do not show any overt signs of disease nor do they have premature morbidity, if they are diagnosed early, but, more often than not, the condition is diagnosed only at autopsy.<ref>[http://digestive.niddk.nih.gov/ddiseases/pubs/hemochromatosis/index.htm Hemochromatosis-Diagnosis] {{Webarchive|url=https://web.archive.org/web/20070318063028/http://digestive.niddk.nih.gov/ddiseases/pubs/hemochromatosis/index.htm |date=18 March 2007 }} National Digestive Diseases Information Clearinghouse, National Institutes of Health, U.S. Department of Health and Human Services</ref>

Presently, the classic triad of cirrhosis, bronze skin, and diabetes is less common because of earlier diagnosis.<ref name="pmid15175440"/>

The more common clinical manifestations include:<ref name="Iron Overload and Hemochromatosis"/><ref name="pmid15175440"/><ref>[http://digestive.niddk.nih.gov/ddiseases/pubs/hemochromatosis/index.htm Hemochromatosis] {{Webarchive|url=https://web.archive.org/web/20070318063028/http://digestive.niddk.nih.gov/ddiseases/pubs/hemochromatosis/index.htm |date=18 March 2007 }} National Digestive Diseases Information Clearinghouse, National Institutes of Health, U.S. Department of Health and Human Services</ref><ref>{{cite web |url=http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=2 |title=Hemochromatosis: Symptoms |work=Mayo Foundation for Medical Education and Research (MFMER) |access-date=17 March 2007 |archive-date=30 April 2008 |archive-url=https://web.archive.org/web/20080430123516/http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=2 |url-status=live }}</ref>
* [[Fatigue (medical)|Fatigue]]
* [[Malaise]]
* Joint [[pain]] (mainly knee and hand)
* [[Abdominal pain]]
* [[Hyperpigmentation|Bronze or gray skin color]] (for this the illness was named "bronze diabetes" when it was first described by [[Armand Trousseau]] in 1865)
* [[Liver]] fibrosis or [[cirrhosis]] (with an increased risk of [[hepatocellular carcinoma]]): Liver disease is always preceded by evidence of liver dysfunction, including elevated serum enzymes specific to the liver, [[Nail clubbing|clubbing of the fingers]], [[leuconychia]], [[asterixis]], [[hepatomegaly]], [[palmar erythema]], and [[spider naevi]]. Cirrhosis can also present with [[jaundice]] (yellowing of the skin) and ascites.
* [[Diabetes mellitus type 2]]: HH patients have [[insulin resistance]] for liver disease, and poor [[insulin]] secretion due to pancreatic damage from [[iron]] deposition.
* [[Erectile dysfunction]] and [[hypogonadism]], resulting in decreased [[libido]], [[amenorrhea]]
* Congestive [[heart failure]], [[Heart arrhythmia|abnormal heart rhythms]], or [[pericarditis]]
* [[Arthritis]] of the hands (especially the second and third [[metacarpophalangeal joint]]s), but also the [[knee joint|knee]] and [[shoulder joint|shoulder]] [[joint]]s
* Weight loss

Less common findings including:
* [[Amnesia|Memory loss]]
* [[Hair loss]]
* [[Splenomegaly]]
* [[adrenal insufficiency]]
* [[Deafness]]<ref name=Jones_1983>{{cite journal |vauthors=Jones H, Hedley-Whyte E |s2cid=26103887 |title=Idiopathic hemochromatosis (IHC): dementia and ataxia as presenting signs |journal=Neurology |volume=33 |issue=11 |pages=1479–83 |year=1983 |pmid=6685241 |doi=10.1212/WNL.33.11.1479}}</ref>
* [[Dyskinesia]]s, including [[Parkinsonian]] symptoms<ref name=Jones_1983 /><ref name=Costello_2004>{{cite journal |vauthors=Costello D, Walsh S, Harrington H, Walsh C |title=Concurrent hereditary haemochromatosis and idiopathic Parkinson's disease: a case report series |journal=J Neurol Neurosurg Psychiatry |volume=75 |issue=4 |pages=631–3 |year=2004 |pmid=15026513 |doi=10.1136/jnnp.2003.027441 |pmc=1739011}}</ref><ref name=Nielsen_1995>{{cite journal |vauthors=Nielsen J, Jensen L, Krabbe K |title=Hereditary haemochromatosis: a case of iron accumulation in the basal ganglia associated with a parkinsonian syndrome |journal=J Neurol Neurosurg Psychiatry |volume=59 |issue=3 |pages=318–21 |year=1995 |pmid=7673967 |doi=10.1136/jnnp.59.3.318 |pmc=486041}}</ref>
* Dysfunction of certain [[endocrine organs]]:
** [[Parathyroid gland]] (leading to [[hypocalcaemia]])
** [[Pituitary gland]]: secondary [[hypothyroidism]], secondary [[hypogonadism]]
** [[Adrenal gland]]
* An increased susceptibility to certain [[infectious disease]]s caused by [[siderophilic bacteria|siderophilic microorganisms]]:
** ''[[Vibrio vulnificus]]'' infections from eating [[seafood]] or wound infection<ref name="pmid19349902">{{cite journal |vauthors=Barton JC, Acton RT |s2cid=35800188 |title=Hemochromatosis and Vibrio vulnificus Wound Infections |journal=J. Clin. Gastroenterol. |volume= 43|issue= 9|pages= 890–893|date=April 2009 |pmid=19349902 |doi=10.1097/MCG.0b013e31819069c1 }}</ref>
** ''[[Listeria monocytogenes]]''
** ''[[Yersinia enterocolica]]''
** ''[[Salmonella enterica]]'' (serotype Typhymurium)<ref name="pmid18684194">{{cite journal  |vauthors=Jolivet-Gougeon A, Loréal O, Ingels A, etal |title=Serum transferrin saturation increase is associated with decrease of antibacterial activity of serum in patients with HFE-related genetic hemochromatosis |journal=Am. J. Gastroenterol. |volume=103 |issue=10 |pages=2502–8 |date=October 2008 |doi=10.1111/j.1572-0241.2008.02036.x |pmid=18684194 |s2cid=23383278 }}</ref>
** ''[[Klebsiella pneumoniae]]''
** ''[[Escherichia coli]]''
** ''[[Rhizopus arrhizus]]''
** ''[[Mucor]]'' species
** ''[[Aspergillus fumigatus]]''
** [[Cytomegalovirus]]
** [[Hepatitis B virus]]
** [[Hepatitis C virus]]

In the hereditary hemochromatosis (HH or HHC), males are usually diagnosed after their forties and fifties, and women some decades later, during [[menopause]]. The severity of clinical disease varies considerably. Some evidence suggests that hereditary haemochromatosis patients affected with other liver ailments such as hepatitis or alcoholic liver disease have worse liver disease than those with either condition alone.  Also, juvenile form of primary haemochromatosis (Hemochromatosis type 2) present in childhood with the same consequences of iron overload.{{citation needed|date=November 2021}}

===End-organ damage===

Iron is stored in the liver, pancreas and heart.
Long-term effects of haemochromatosis on these organs can be serious, even fatal when untreated.<ref>{{cite web |url=http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=6 |title=Hemochromatosis: Complications |work=Mayo Foundation for Medical Education and Research (MFMER) |access-date=17 March 2007 |archive-date=7 March 2008 |archive-url=https://web.archive.org/web/20080307063708/http://www.mayoclinic.com/health/hemochromatosis/DS00455/DSECTION=6 |url-status=live }}</ref>

Since the liver is a primary storage area for iron and naturally accumulates excess iron over time, it is likely to be damaged by iron overload.
Toxins may accumulate in the blood and eventually affect mental functioning due to increased risk of [[hepatic encephalopathy]].
Together, they can increase the risk of liver cancer to one in three persons.

If excess iron in the heart interferes with its ability to circulate enough blood, a number of problems can occur, including (potentially fatal) [[congestive heart failure]]. The condition may be reversible when haemochromatosis is treated and excess iron stores are reduced. [[Arrhythmia]] or abnormal heart rhythm can cause heart palpitations, chest pain, and light-headedness, and is occasionally life-threatening. This condition can often be reversed with treatment.{{citation needed|date=July 2020}}

The pancreas, which also stores iron, is very important in the body's mechanisms for sugar [[metabolism]]. [[Diabetes]] affects the way the body uses blood sugar ([[glucose]]), and diabetes is, in turn, the leading cause of new blindness in adults and may be involved in [[kidney failure]].<ref>{{Cite journal |last1=Hong |first1=Jingyao |last2=Surapaneni |first2=Aditya |last3=Daya |first3=Natalie |last4=Selvin |first4=Elizabeth |last5=Coresh |first5=Josef |last6=Grams |first6=Morgan E. |last7=Ballew |first7=Shoshana H. |date=2021-07-07 |title=Retinopathy and Risk of Kidney Disease in Persons With Diabetes |journal=Kidney Medicine |volume=3 |issue=5 |pages=808–815.e1 |doi=10.1016/j.xkme.2021.04.018 |issn=2590-0595 |pmc=8515075 |pmid=34693260}}</ref>

Haemochromatosis may lead to [[cirrhosis]] and its complications, including bleeding from dilated veins in the [[esophagus]] ([[esophageal varices]]) and [[stomach]] ([[gastric varices]]) and severe fluid retention in the [[abdomen]] ([[ascites]]).
Severity of [[periodontal disease]] is associated with high [[transferrin saturation]] in haemochromatosis patients.<ref>{{cite journal |last1=Meuric |first1=Vincent |last2=Lainé |first2=Fabrice |last3=Boyer |first3=Emile |last4=Le Gall-David |first4=Sandrine |last5=Oger |first5=Emmanuel |last6=Bourgeois |first6=Denis |last7=Bouchard |first7=Philippe |last8=Bardou-Jacquet |first8=Edouard |last9=Turmel |first9=Valérie |last10=Bonnaure-Mallet |first10=Martine |last11=Deugnier |first11=Yves |title=Periodontal status and serum biomarker levels in HFE haemochromatosis patients. A case-series study |journal=Journal of Clinical Periodontology |date=September 2017 |volume=44 |issue=9 |pages=892–897 |doi=10.1111/jcpe.12760 |pmid=28586532 |s2cid=35455901 |url=https://hal-univ-rennes1.archives-ouvertes.fr/hal-01614700/file/Meuric%20et%20al.%20-%20Periodontal%20status%20and%20serum%20biomarker%20levels%20in%20H.pdf |access-date=22 May 2020 |archive-date=20 July 2018 |archive-url=https://web.archive.org/web/20180720213547/https://hal-univ-rennes1.archives-ouvertes.fr/hal-01614700/file/Meuric%20et%20al.%20-%20Periodontal%20status%20and%20serum%20biomarker%20levels%20in%20H.pdf |url-status=live }}</ref><ref>{{cite journal |last1=Boyer |first1=Emile |last2=Le Gall-David |first2=Sandrine |last3=Martin |first3=Bénédicte |last4=Fong |first4=Shao Bing |last5=Loréal |first5=Olivier |last6=Deugnier |first6=Yves |last7=Bonnaure-Mallet |first7=Martine |last8=Meuric |first8=Vincent |title=Increased transferrin saturation is associated with subgingival microbiota dysbiosis and severe periodontitis in genetic haemochromatosis |journal=Scientific Reports |date=December 2018 |volume=8 |issue=1 |page=15532 |doi=10.1038/s41598-018-33813-0 |pmid=30341355 |pmc=6195524 |bibcode=2018NatSR...815532B }}</ref>