Hereditary haemochromatosis type 1 (HFE-related Hemochromatosis) is a genetic disorder characterized by excessive intestinal absorption of dietary iron, resulting in a pathological increase in total body iron stores. Humans, like most animals, have no means to excrete excess iron, with the exception of menstruation which, for the average woman, results in a loss of 3.2 mg of iron.
Excess iron accumulates in tissues and organs, disrupting their normal function. The most susceptible organs include the liver, heart, pancreas, skin, joints, gonads, thyroid and pituitary gland; patients can present with cirrhosis, polyarthropathy, hypogonadism, heart failure, or diabetes.
There are five types of hereditary hemochromatosis: type 1, 2 (2A, 2B), 3, 4 and 5, all caused by mutated genes. Hereditary hemochromatosis type 1 is the most frequent, and unique related to the HFE gene. It is most common among those of Northern European ancestry, in particular those of Celtic descent. The disease is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not express signs or symptoms of the condition. In this situation, the otherwise unaffected parents are referred to as carriers.
Signs and symptoms
Haemochromatosis is 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.
Presently, the classic triad of cirrhosis, bronze skin, and diabetes is less common because of earlier diagnosis.
The more common clinical manifestations include: Fatigue Malaise Joint pain (mainly knee and hand) Abdominal pain 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, 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, abnormal heart rhythms, or pericarditis Arthritis of the hands (especially the second and third metacarpophalangeal joints), but also the knee and shoulder joints Weight loss
Less common findings including: Memory loss Hair loss Splenomegaly adrenal insufficiency Deafness Dyskinesias, including Parkinsonian symptoms Dysfunction of certain endocrine organs: Parathyroid gland (leading to hypocalcaemia) Pituitary gland: secondary hypothyroidism, secondary hypogonadism Adrenal gland An increased susceptibility to certain infectious diseases caused by siderophilic microorganisms: Vibrio vulnificus infections from eating seafood or wound infection Listeria monocytogenes Yersinia enterocolica Salmonella enterica (serotype Typhymurium) 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.
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.