Ferroportin's disease - symptoms, causes, treatment | NERD (2023)

FAQs

What are the symptoms of ferroportin disease? ›

The specific symptoms related to these disorders can vary depending upon the location and extent of iron accumulation. Common symptoms include fatigue, abdominal pain, lack of sex drive, joint pain, and heart abnormalities.

Abstract. Ferroportin Disease (FD) is an autosomal dominant hereditary iron loading disorder associated with heterozygote mutations of the ferroportin-1 (FPN) gene. It represents one of the commonest causes of genetic hyperferritinemia, regardless of ethnicity.

Ferroportin (Fpn) emerges as a critical transporter in terms of iron acquisition and transfer of iron between cell types, as it is the only known transporter that exports elemental iron from cells. Fpn is essential to distribute iron between tissues and for iron absorption into the organism.

Ferroportin is found on the basolateral membranes of intestinal epithelia of mammals, including: Enterocytes in the duodenum. Hepatocytes. Macrophages of the reticuloendothelial system.

The body has no easy way to dispose of extra iron. The most effective way to get rid of excess iron is blood loss. Therefore, menstruating women are less likely to experience iron overload. Likewise, those who donate blood frequently are at lower risk.

Hepcidin inhibits ferroportin (SLC40A1), the only known cellular iron exporter (7, 8).

Hemochromatosis (he-moe-kroe-muh-TOE-sis) causes your body to absorb too much iron from the food you eat. Excess iron is stored in your organs, especially your liver, heart and pancreas. Too much iron can lead to life-threatening conditions, such as liver disease, heart problems and diabetes.

Hepcidin binding to ferroportin induces its internalization and degradation, resulting in cellular iron retention and decreased iron export.

What is the gene for ferroportin? ›

The SLC40A1 gene provides instructions for making a protein called ferroportin. This protein is involved in the process of absorbing iron that the body receives from food. Ferroportin transports iron obtained from the diet that is absorbed through the walls of the small intestine into the bloodstream.

Hepcidin binds to the iron exporter ferroportin, inducing its degradation and thus preventing iron entry into plasma.

The most commonly used treatment for haemochromatosis is a procedure to remove some of your blood, known as a venesection or phlebotomy. The procedure is similar to giving blood. You lie back in a chair and a needle is used to drain a small amount of blood, usually about 500ml, from a vein in your arm.

Excessive iron can be damaging to the gastrointestinal system. Symptoms of iron toxicity include nausea, vomiting, diarrhea and stomach pain. Over time, iron can accumulate in the organs, and cause fatal damage to the liver or brain.

The liver is the organ most affected by hemochromatosis, because of its relatively large blood flow. Blood from the portal circulation (which comes from the intestines) goes straight to the liver. Once the body absorbs iron, it is not lost until blood is lost.

Many patients also have periodic limb movements in sleep (PLMS), and they may complain of insomnia and/or hypersomnia. Hereditary haemochromatosis is an autosomal recessive disease of iron metabolism in which increased intestinal absorption of iron leads to iron deposition in multiple organs.

Type 1 hemochromatosis results from mutations in the HFE gene, and type 2 hemochromatosis results from mutations in either the HJV or HAMP gene. Mutations in the TFR2 gene cause type 3 hemochromatosis, and mutations in the SLC40A1 gene cause type 4 hemochromatosis.

The classic form of hemochromatosis is most common in Caucasians of Northern European descent. It is a genetic disease that may be found in families.

Ferroportin transports only Fe²⁺ (27), whereas transferrin in portal blood will bind only Fe³⁺. Efficient transfer of iron to portal blood transferrin is thought to involve an oxidation step catalyzed by a ferroxidase.

What pulls iron out of the body? ›

All grains, legumes, seeds, and nuts contain phytic acid, or phytate, which reduces iron absorption. Eating foods high in phytates, such as beans, nuts, and whole grains, reduces the absorption of nonheme iron from plant foods. As a result, it may reduce total iron levels in the body.

Hematologists (blood disease specialists)

Certain infections, which may be viral or bacterial. Medicines, such as penicillin, antimalarial medicines, sulfa medicines, or acetaminophen. Blood cancers. Autoimmune disorders, such as lupus, rheumatoid arthritis, or ulcerative colitis.

Consistently, ferroportin (FPN), the only known vertebrate iron exporter identified to date, is highly expressed in splenic macrophages, Kupffer cells, hepatocytes, and intestinal epithelial cells, from which it transports iron into the blood.

Ferroportin exports iron from duodenal enterocytes that absorb dietary iron, from iron-recycling macrophages in the spleen and the liver, and from iron-storing hepatocytes. Hepcidin blocks iron export through ferroportin, causing hypoferremia.

Iron overload occurs when there are excess stores of iron in the body. Primary iron overload is often inherited. Secondary iron overload usually arises from causes such as transfusion, hemolysis, or excessive parenteral and/or dietary consumption of iron.

Leukemia cells show increased iron uptake and decreased iron efflux, leading to elevated cellular iron levels.

Ferritin is often elevated in the serum of cancer patients including those with neuroblastoma (63), Hodgkinson's lymphoma (64), cervical (65), oral squamous cell (66), renal cell (67), T cell lymphoma (68), CRC (69), and breast (70) cancers and were often associated with increased tumor grade and shorter survival.

The most important inhibitors of iron uptake are phytic acid/phytates, polyphenols/tannins, proteins from soya beans, milk, eggs, and calcium.

What are two factors that inhibits iron absorption? ›

While phytic acid, sodium oxalate, and sodium silicate decrease iron absorption, ascorbic acid has the ability to counteract their inhibitory effects. Inclusion of meat to the vegetable puree significantly increased the nonheme iron absorption.

Iron absorption is regulated by the hepatic peptide hormone hepcidin. Hepcidin also controls iron release from cells that recycle or store iron, thus regulating plasma iron concentrations. Hepcidin exerts its effects through its receptor, the cellular iron exporter ferroportin.

This may include inflammatory disorders, liver disease (particularly non-alcoholic steatohepatitis (NASH)/fatty liver), alcohol excess, malignancy, renal failure, and metabolic syndrome, which are each more common than hemochromatosis.

Avoid processed meat, offal and blood containing foods. Eat no more than 200 g meat from poultry per week. Choose fish, eggs, vegetables and protein rich legumes the other days. Eat fish two to four times a week as main course, 350 - 500 g fish per week, of which half should be fat fish.

Ferritin is a multisubunit protein capable of binding up to 4,000 iron atoms and serves principally as an iron-storage protein, though it may also serve to detoxify iron. In iron-rich tissues ferritin is largely degraded and the iron is converted to haemosiderin.

The TMPRSS6 gene encodes a particular liver protein that regulates the production of hepcidin, an iron regulatory hormone. In children with IRIDA, the TMPRSS6 mutation causes elevated levels of hepcidin, which ultimately impairs the body's ability to both absorb and use iron.

The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria. Lactoferrin is a nutrient classically found in mammalian milk. It binds iron and is transferred via a variety of receptors into and between cells, serum, bile, and cerebrospinal fluid.

Extreme fatigue. Weakness. Pale skin. Chest pain, fast heartbeat or shortness of breath.

If you have anemia, your body does not get enough oxygen-rich blood. The lack of oxygen can make you feel tired or weak. You may also have shortness of breath, dizziness, headaches, or an irregular heartbeat.

Undiagnosed or untreated iron-deficiency anemia may cause serious complications such as fatigue, headaches, restless legs syndrome, heart problems, pregnancy complications, and developmental delays in children. Iron-deficiency anemia can also make other chronic conditions worse or cause their treatments to work poorly.

Can low iron cause joint and muscle pain? ›

Fatigue and neurocognitive symptoms often raise a suspicion of depression. Furthermore, headache and muscle and joint pain associated with iron deficiency are repeatedly considered migraine and fibromyalgia syndrome, respectively 3, 19.

Turmeric is among the spices known to inhibit iron absorption by 20%-90% in humans, reducing iron absorption in a dose-dependent manner [10]. The stoichiometric qualities of turmeric indicate it could bind nearly all absorbable iron and cause iron deficiency, and it does so in mice [3].

Iron Content

Stouts, porters, and other darker beers contain the highest concentrations of iron. Lagers, pale ales and other light-colored beers contain about three-quarters of the iron of darker beers, whereas non-alcoholic beers have about half the iron content of dark beers.

With the buildup of harmful levels of iron, hemochromatosis can cause symptoms including feeling tired or weak, pain in the joints, loss of interest in sex or erectile dysfunction, pain in the abdomen over the liver, and darkening of skin color.

Transferrin saturation values greater than 45% are considered too high. Serum ferritin. This test measures the amount of iron stored in your liver. If the results of your serum transferrin saturation test are higher than usual, your health care provider may check your serum ferritin.

After those early symptoms, other serious complications can develop within 48 hours after the iron overdose, such as: dizziness. low blood pressure and a fast or weak pulse.

Prognosis. Among affected persons, the iron concentration in the liver is a major determinant of the risk of cirrhosis (scarring) of the liver and, in turn, of hepatocellular carcinoma (liver cancer). These are the two major causes of death associated with hereditary hemochromatosis.

Men with type 1 or type 4 hemochromatosis typically develop symptoms between the ages of 40 and 60, and women usually develop symptoms after menopause. Type 2 hemochromatosis is known as a juvenile-onset disorder because symptoms often begin in childhood.

People with hemochromatosis are also more susceptible to blood stream infections. Do not avoid fruits, vegetables, nuts, grains, rice, and beans – These foods do contain iron, but mostly in non-heme form, which is more difficult to absorb than heme iron.

Hemochromatosis may cause belly pain, weakness, tiredness, and weight loss. It also can scar the liver, cause joint pain, and darken the skin. In late stages, it can damage the heart and joints, and can cause diabetes. Symptoms of hemochromatosis often do not appear until a person is 40 to 60 years old.

What does your skin look like with hemochromatosis? ›

Skin pigmentation is often one of the first signs of the disease and may precede the other features by many years. Hyperpigmentation is most evident on sun-exposed skin, particularly on the face. The colour of skin can be slate grey or brownish bronze. Partial loss of body hair; the pubic region is most affected.

Inhibitors of iron absorption include phytate, which is a compound found in plant-based diets that demonstrate a dose-dependent effect on iron absorption. Polyphenols are found in black and herbal tea, coffee, wine, legumes, cereals, fruit, and vegetables and have been demonstrated to inhibit iron absorption.

Phytates and fibres found in wholegrains such as bran can reduce the absorption of iron and other minerals. Inadequate vitamin A in your diet could lead to iron deficiency because vitamin A helps to release stored iron. Calcium and phosphorus reduce the absorption of plant-sourced (non-haem) iron.