Aidan: Text replacement - "Clinical Presentation" to "Clinical Manifestations"

2020-07-21T01:44:45Z

Text replacement - "Clinical Presentation" to "Clinical Manifestations"

← Older revision		Revision as of 01:44, 21 July 2020
Line 20:		Line 20:
	* 10% of those homozygous for C282Y develop symptoms		* 10% of those homozygous for C282Y develop symptoms

	== Clinical ~~Presentation~~ ==		== Clinical Manifestations ==

	=== History ===		=== History ===

Maintenance script: Imported from text file

2020-07-04T01:17:38Z

Imported from text file

New page

== Definition ==

Recessive genetic disorder to iron handling that is characterized by elevated iron saturation and high ferritin and that causes progressive end-organ damage, most commonly liver, pancreas, and heart.

== Etiology ==

* Most commonly caused by homozygous C282Y mutation of the HFE gene
** Only 10% of homozygotes will have iron overload
* Can also present in compound heterozygotes of HFE gene
* Non-HFE-associated iron overload
** Hemojuvelin (HJV)
** Transferrin receptor-2 (TfR2)
** Ferroportin (SLC40A1)
** Hepcidin (HAMP)
** African iron overload

== Epidemiology ==

* Most common genetic cause of cirrhosis
* 10% of those homozygous for C282Y develop symptoms

== Clinical Presentation ==

=== History ===

* Asymptomatic
** Abnormal serum iron studies on routine screening chemistry panel
** Evaluation of abnormal liver tests
** Identified by family screening
* Nonspecific, systemic symptoms
** Weakness
** Fatigue
** Lethargy
** Apathy
** Weight loss
* Specific, organ-related symptoms
** Abdominal pain (hepatomegaly)
** Arthralgias (arthritis)
** Diabetes (pancreas)
** Amenorrhea (cirrhosis)
** Loss of libido, impotence (pituitary, cirrhosis)
** Congestive heart failure
** Arrhythmias

=== Physical exam ===

* Liver
** Hepatomegaly
** Cutaneous stigmata of chronic liver disease
** Splenomegaly
** Liver failure: ascites, encephalopathy, and associated features
* Joints Arthritis
** Joint swelling
** Chondrocalcinosis
* Heart
** Dilated cardiomyopathy
** Congestive heart failure
* Skin
** Increased pigmentation
** Porphyria cutanea tarda
* Endocrine
** Testicular atrophy
** Hypogonadism
** Hypothyroidism

== Investigations ==

<pre class="mermaid">graph TD;

invest["Serum transferrin saturation (TS) and ferritin"]

tsnorm["TS <45% and normal ferritin"]
tsup["TS ≥45% and/or high ferritin"]
fhx["First-degree relative with HH"]
noeval["No further evaluation"]
genotype["HFE genotyping"]

invest --> tsnorm
tsnorm --> noeval

invest --> tsup
tsup --> genotype

fhx --> genotype
</pre>
* Initial workup is '''ferritin''' and '''serum transferrin saturation'''
** If ferritin is above upper limit of normal, or if transferrin saturation is ≥45%, then do HFE mutation analysis
** Transferrin saturation = serum iron concentration ÷ total iron binding capacity
* HFE mutation analysis
** Done for all first-degree relatives of an index case
** Done for all patients with elevated ferriting or TS ≥45%
** Important results:
*** Homozygous C282Y
*** Compound heterozygous C282Y/H63D
*** Homozygous H63D/H63D generally don't have iron overload
* Iron/transferrin saturation >60% in men or >50% in women
** Most sensitive and cost-effective test
* If cirrhosis develops, monitor closely for hepatocellular carcinoma

== Management ==

* Phlebotomy to target ferritin of 50-100
** But need to prevent hematocrit or hemoglobin dropping more than 20% of prior level

== Further Reading ==

* Bacon BR ''et al''. [https://doi.org/10.1002/hep.24330 Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases]. ''Hepatology''. 2011;54(1):328-43.

[[Category:Hematology]]
[[Category:Gastroenterology]]

Hereditary hemochromatosis - Revision history

Aidan: Text replacement - "Clinical Presentation" to "Clinical Manifestations"

Maintenance script: Imported from text file