The clinical manifestations of this disease, and other forms of excess iron in the body, mainly related to excessive iron deposition in tissues, especially liver, heart, pancreas, and pituitary.
Epidemiological Epidemiology:
• General population General population:
I think in the past that the blood pigment genetic disease a rare disease where he was taken into account only when there are unusual events (such as bronze diabetes). When estimated that disease is transmitted as an adjective recessive physical conjunction with the HLA-A are positioned on the short arm of chromosome 6, it was possible to carry out studies and analysis of family minutes, these studies showed that the percentage of saturation Turanseverin (concentration of serum iron / total capacity Association for Iron) at more than 60% of men and 50% of the women identified a defect in iron metabolism (symmetric and skewed Alloaqah) almost 95% accuracy.
The survey showed that the proportion of population presence Alloaqah variant form is 10% in the Caucasian race in the United States and Western Europe, and the symmetric Alloaqah Vnspth does not exceed 5 per 1000 (0.5%). And found a higher proportion of 1% in the survey considered that 60% of patients who have a high rate of satisfaction with the normal concentration of serum iron to have a case of early disease of the blood pigment gene.
It is well known now that a majority of the patients diagnosed with this disease are Emtemathlo Alloaqah of the C282Y mutation occurring on the gene HFE.
• genetic defects is HFE (Gene Defects):
Although the majority of the patients diagnosed with blood pigment clinically disease have mutations in the gene HFE. There are some other genetic defects that cause the disease are explained in the following table:
1. Blood pigment disease infantile Juvenile Hemochromatosis:
Is a form of the disease is uncommon pigment occurs in childhood and moves my body is also recessive, is characterized that appear earlier and more severe than that of the typical and differs genetically (not caused by a mutation in the gene HFE). Most of the cases recorded in Italy.
In the study including 6 female and two male patients were selected from 5 families Greek has not been for some onion and spread the disease pigment infantile, it was found that the signs and symptoms began at the age between 19-39 and included inflammation of the joints deformed and lightly, especially arthritis metacarpophalangeal second, third, and hypogonadism with hypogonadotropism (Hypogonadotropic Hypogonadism), high liver enzymes with fibrosis or cirrhosis, and decreased bone density, arthritis Mitrkie was independent of treatment Balvsadh.
And in all cases and, in general, individuals with the disease (infantile disease pigment), they are more likely to review the doctor with poor cardiac muscle, and decrease with glucose, and lack of reproductive glands of their review of more severe hepatic impairment.
2. African Americans, Africans Americans:
Is a disease in which iron overload, with clinical manifestations and liver biopsy for genetic disease blood pigment, was described in four African-American. Is not specified, a pathological physiology, but the tissue and cellular distribution of iron which is different than in the typical disease of the pigment associated with HLA. It has been suggested the existence of genes other than HFE affects iron metabolism of the body.
Pathophysiology Pathophysiology:
Tabiein in people, the absorption of heme iron and iron non-HEMI (located outside the heme iron) inversely proportional to iron stores. This is reflected in the serum ferritin concentration. The iron is thrown through sweating, and dead skin cells, and gastrointestinal tract rate of 1 mg / day. And lose the adult women before menopause 0.5-1 mg of additional iron because of menstruation, and is compensated for this deficiency in Western societies by absorbing 10 percent of 10-20 mg iron present in the diet of women.
Genetic disease characterized by pigment replication Alloaqah increase absorption of iron and heme Allahimi. On the contrary, people Tabiein, the absorption of heme iron is not about to Eitnzm and stores iron. This leads to progressive accumulation of iron due to the lack of a natural mechanism to put excess iron from the body after absorption.
Simple calculations and understand the cause of symptoms in late-onset disease of genetic blood pigment until after the age of forty in males and more females. It absorbs the male patient disease pigment (symmetric Alloaqah) 2-4 mg iron per day (in terms of quantity of natural necessary to compensate for the loss of iron, 1 mg per day), and assuming that it absorbs 4 mg per day, the retention of iron (3 mg per day plus the need) will lead entirely to the accumulation of iron at a rate of 1 gram per year. If not, there are great needs for iron activity after growth in adulthood, it will not get the accumulation of iron more than 20 g until the age of 40-50 years. When you reach this level of iron, patients show symptoms of disease pigment that will be remembered later. On the other hand, women ages display same symptoms later than men and the reason for this is the additional loss of iron through menstruation, pregnancy and lactation.
Clinical CLINICAL MANIFESTATIONS:
The iron verifier in the disease pigment bloody HH is deposited mainly in cells Albaranchemah (shipboard), and its accumulation in the cells, retinal endothelial occurs at a late stage of the disease, contrary to what happens when you overload of iron in blood transfusion, where deposited iron in the cells, retinal endothelial first and then Albranchimih in the cells.
The clinical manifestations include the accumulation of iron in the tissues: liver disorders, skin pigmentation, diabetes, arthropathy, impotence in males, the magnitude of heart attack with or without heart failure or delivery disorders.
One of the reports, for example: the values of (251) HH patients diagnosed from 1959 to 1992 Vlouhzt abnormalities following when applying:
• liver function abnormalities and 75%
• weakness, drowsiness 74%
• skin hyperpigmentation 70%
• Diabetes 48%
• joint pain Arthralgia 44%
• male impotence Impotence in males 45%
• abnormalities on ECG 31%
In another report included (2851) accidental person for 10 years on average before diagnosis, examined in a survey, found that the most common symptoms are: extreme fatigue (46%), joint pain (44%), low sexual desire (26%).
- Reflect the association of skin pigmentation and melanin deposited iron.
- The classic three-spoke: cirrhosis of the liver, diabetes, skin pigmentation (bronze diabetes) in the late stage of the disease, ie, in the time it reaches the total content of iron the body for more than 20 grams (usually five times greater).
However, HH had to change, where most patients are diagnosed there is a rise in serum iron levels observed in the list of routine chemical testing or examination performed by diagnosis related to HH!!!!
In two studies: nearly 75% of the patients were not casual when they apply, with a low percentage (less than 25%) of cirrhosis of the liver, diabetes, hyper pigmentation of the skin. The result was: The association between genotypes of different for HH the one hand and clinical findings (k accident liver disease, inflammation of the liver, adipose nonalcoholic nonalcoholic steatohepatitis, porphyria cutaneous porphyria cutanea tarda, diabetes, arthritis) on the other hand, is not of importance uncertain.
In a third study evaluated (214) relatives of people with HH symmetric Alloaqah who discovered during the follow-up (291) Mstfatt person (the first to draw attention to the disease of several individuals) symmetric Alloaqah.
Values of these relatives according to the presence of iron overload and cases of the disease (cirrhosis of the liver, cirrhosis, and high levels of amino transferase, arthropathy)
Iron overload was present in 85% and 68% in men and women respectively, while the prevalence of cases of the disease by 38% and 10% respectively also.
These observations and the results stand out and highlight the importance of early diagnosis of the patient as well as for any relatives of the wounded people are not diagnosed.
• incidence of liver Liver disease:
Accompanied by progressive deposition of iron with Hepatomegaly, elevated liver enzymes, to increase the likelihood of development of fibrosis or cirrhosis of the liver.
And reverse these changes occur after iron removal treatment therapeutic iron removal and shows this effect is often at an early therapeutic intervention for the disease, but can occur even in patients who came to the stage of liver cirrhosis or varicose veins.
In one of the reports of 120 patients living with liver cirrhosis and HH and 120 patients infected by necrotic hepatic cirrhosis, 25% of them have varices:
Accompanied by treatment with (a few vein phlebotomy) with improved and the reflection of varicose veins in 26% of HH patients versus 5% in patients with cirrhosis of the liver before necrolysis.
- Accompanied by aggravation of hypertension jugular vein in patients with sepsis HH hepatitis Almtaih (example: HBV, HCV) and on 16 in 22 cases.
Iron overload in HH also increases the ability to develop alcoholic liver disease.
This effect may be related to the ability of iron to serve as the electron donor, which speeds up the generation of interactive media Alooxgenih unstable resulting in damage to the supporting membrane, and the increased formation of free radicals also lead to accelerated generation of chemical Jazbat neutrophils leading to enhanced inflammatory response.
Although the number of patients under study so far is small, the presence of HH caused by overload of iron may also have an impact on the revitalization of cirrhosis of the liver in patients with sepsis with hepatitis HCV, is similar to the fibrosis, seen in patients with overload iron with thalassemia major and HIV infection.
Should be for all patients who suffer from cirrhosis of the liver to undergo diagnostic endoscopy to document the presence of varicose veins and determine the amount of risk in the event of bleed.
Must also take into account the patients with high risk for the development of bleeding varicose veins of primary prevention in order to achieve them using propranolol or nadolol.
Hepatocellular carcinoma Hepatocellular carcinoma:
Hepatocellular carcinoma (HCC) is one of the most serious complications of excess iron deposition in the liver.
The Many studies have shown an increased risk of hepatocellular carcinoma in patients who suffer from genetic disease blood pigment, although the higher estimates of the size of the risk has changed a lot of up to 20 times to 200 times increase!!.
In one of the largest population-based studies to address this issue estimated that the risk increased by almost 20 times compared with the general population (95% CI). This was the biggest risk in men, but did not increase between first-degree relatives.
• Diabetes Diabetes mellitus:
Diabetes mellitus (DM) present in about 50% of patients with HH cross, and spoke this complication due to the accumulation of iron in the pancreas gradually and shows this imbalance selectively relative in the cells of the pancreas beta β to decrease the secretion of insulin and peptide C, while the function of alpha cell α seem to sound as evidenced by the increase in serum glucagon levels are similar to those levels that have appeared in type 1 diabetes.
Observed in patients suffering from HH, and DM who require insulin therapy in a decrease in needs of it after removing the iron treatment.
A separate issue is whether all patients with DM should be screened for the denial or the presence of HH:
• In the Italian study values (894) patient diabetes (mostly type 2) for HH.
All patients underwent screening for biochemical Turansvirin saturation and serum ferritin, and after exclusion of secondary causes leading to overload of iron in the blood, taken from the liver biopsy to confirm the diagnosis, was the spread of HH 1.3%, and six times in the general population.
The process remains a need to examine all patients with diabetes for HH is uncertain, since other studies did not confirm the increased incidence of HH in patients with type 2 diabetes.
Most patients who suffer from diabetes secondary to disease of blood pigment have other signs of HH such as liver disease or hyperpigmentation of the skin, and then, patients who do not have these signs are less likely to have the presence of HH.
The Alloaqah Heterozygotes heterozygous heterozygous patients with blood pigment also increases the risk for development of DM.
In a study based on the population of 555 men from Finland was the result:
6.9% of them were carrying the gene of HH, with an increased risk of association with type 2 DM and its associated type 2 (odds ratio 3.5).
• arthropathy:
Disease may be associated with pigment bloody demonstrations articulated a broad-spectrum resulting from the accumulation of iron in the tissues of the joint, leading to symptoms similar to those resulting from the deposition of calcium pyrophosphate crystals in the joints (false gout pseudogout, chondrocalcinosis,).
It also results in the accumulation of iron in the joint characteristic X-ray events, as it appears metacarpophalangeal joints (especially the second and third) were cut by the end and vegetations in bone tenaculum.
Unlike other demonstrations of the disease the blood pigment, the arthropathy is not cured by removing iron. In one study involving 129 patients did not respond to treatment Balvsadh phlebotomy only 20 patients of them.
• incidence of heart attack:
May lead to blood pigment disease myocardiopathy expansion dilated cardiomyopathy, which is characterized by heart failure and cardiac conduction disorder (sick sinus syndrome), due to excessive accumulation of iron between the cardiac muscle fibers. Previously the problem was a heart attack the main complaint for 15% of patients with genetic blood disease pigment
Diagnose cardiac injury through clinical history and examination estoppel, and laboratory studies and surveys radial non-invasive. Resonator MRI can reveal increased iron deposition between heart muscle fibers. In case of failure of previous surveys resort to biopsy as a last resort.
Treatment Balvsadh Boukhalebatt iron or lead to improvement in symptoms of left ventricular failure, but the condition of the arrival of the disease to an advanced stage.
Previously believed that the accumulation of iron in excess in the body predisposed to hardening of atherosclerosis atherosclerosis, but the in vivo experiments on mice have shown that increased iron reduce the severity of atherosclerosis by 50%; as Other studies have shown that the likelihood of injury patients disease pigment blood disease, coronary severe one third of the likelihood of people ordinary.
But this is still a controversial topic there are other studies have reached contradictory results, and found a relationship between ischemic myocardiopathy with the accumulation of excess iron in the body or even with a pigment mutation bloody Zaijut heterogeneous.
• inadequate Aloguenad Hypogonadism:
Accumulation of excess iron in the pituitary gland leads to limitations, and therefore to the lack of a secondary Aloguenad (the most important disturbances in the endocrine disease genetic blood pigment). And pretend to weak sexual desire libido and impotence impotence in male patients. Explains the failure Aloguenad lack of bone mass in patients. Has a study of 22 patients found that 10 of them suffering from osteoporosis osteoporosis.
In another study of 89 patients, found that 26 of them have low levels of the hormones testosterone and FSH and LH, which confirms that the deficiencies in these Aloguenad is secondary to pituitary insufficiency.
The shortcomings of the initial Oguenad stemmed from deposition of iron in the testes or ovaries, and gets less than the frequency of secondary deficiencies. The therapy can Balvsadh help the patient to restore normal sexual function, especially if he is under the age of forty.
• Menopause Amenorrhea:
The proportion of infected female patients interruption of menstruation less than male injury Aloguenad failure. In a study of 23 patients with homozygous mutation for the disease the blood pigment, were not any of them suffer from poor sex drive or access to the menopause, menopause before the age of 45 years.
• hypothyroidism:
In a study of 34 of the male patients, 3 of whom were infected with failure hypothyroidism with high levels of the hormone TSH, as revealed in these three antibodies to the thyroid gland, leading to believe that the deposition of iron in the fabric of the thyroid gland and sabotage have led to the exposure to antigens and thus the formation of antibodies anti-thyroid gland.
• cancer outside the liver:
From the installer that the blood pigment disease is associated with increased liver cancer cell hepatocellular carcinoma, but it increases the risk of cancer outside the liver, too?
In a study of 1847 patients and 5973 of first degree relatives, it was found that the risk of liver cancer in patients is 20 times greater than the general population, while there is no significant increase in the risk of other cancers outside the liver. And Tai are still reports that indicate increased likelihood of cancer outside the liver in patients weak and there is clear guidance for follow-up.
• preparedness for some infections:
Blood pigment disease and cirrhosis of the liver and iron overload in patients under the blood of dialysis, it seems factors predispose to infection Balliestiria. The cumulative iron in the macrophages weaken the process of phagocytosis, can also result in the accumulation of iron in the serum to increase the virulence of the bacteria.
Also increases the risk of sepsis Balisanaa inflammatory colon with me and Yersinia enterocolitica. Organelle is the love of Iron and has many features to facilitate the uptake of iron necessary for growth.
It also increases the risk of bacteremia with Vibrio vulnificus, a bacteria nutrient Iron and infection is by eating the seafood is cooked well.
• Clinical events at Mtkhalfa Alloaqah:
The symptoms of iron overload have not uncommon. In a study of 1058 people carrying a mutation heterogeneous Alloaqah to disease pigment blood, about 10% of them have the level of Turanseverin serum high and comparable to what it is when patients - a campaign mutations homozygous. And take a biopsy of the liver of 39 patients, 6 of them and found abnormalities in the biopsy, but 5 those of the 6 have other reasons for poor hepatic (liver inflammation, alcohol ... etc.). Thus, the injury to the liver Mtkhalfa Alloaqah very rare. Studies have shown that other Mtkhalfa Alloaqah at risk of diabetes, cancer of the colon and rectum, and blood malignancies. As is the case when Mtmaathlee Alloaqah, the results of studies on the relationship between mutation Mtkhalfah Alloaqah and increased risk of heart disease is still contradictory.
In the French study included two groups: the first included 492 people carrying C282Y mutation Mtkhalfah Alloaqah (elderly people, average age 103 years). The second group included 492 witnesses from 6 different geographic regions (the average age of the evidence 51 years old). Found that mutations in the general Mtkhalfah Alloaqah blood pigment genetic disease does not predispose to serious disruptions of life-threatening.
0 comments:
Enregistrer un commentaire