Overview

Ferroportin disease is a rare disorder of the iron metabolism and transport system. It is characerised by abnormally high iron retention levels in macrophages in the body.¹ Ferroportin disease results due to variations or mutations of the SLC40A1 gene.This gene encodes the protein Ferroportin-1 which is responsible for transporting iron from inside the cell to the outside of the cell.² The exact effect of the disease on those affected depends entirely on its severity in each case.

What is ferroportin disease?

Ferroportin disease is classified as an iron overload disorder, also referred to as type 4 hemochromatosis. It results in the build up of iron in the body as it cannot be transported correctly outside of the cells. A mutation or issue in the SLC40A1 gene is the cause of ferroportin disease as this gene is responsible for creating the protein ferroportin. Ferroportin is the specalised protein responsible for the correct transportation of iron from inside the cells. 

A malfunction in this gene results in the unwanted build up of iron inside tissues and cells. The exact malfunction can vary the extent and type of ferroportin disease, with some researchers believing the differing ways in which the gene can be affected actually accounts for the formation of two different types of the disorder.³ Symptoms vary from person to person and it is a separate disease entirely from classic hereditary hemochromatosis, even though sometimes used interchangeably. 

Who is at risk of ferroportin disease?

Ferroportin disease is inherited as a dominant genetic condition, meaning the presence of only a single copy of the gene is needed from either parent for the child to inherit the disease. The actual risk of inheriting the disease from an affected parent to their child is only 50% for each pregnancy. 

Ferroportin disease equally affects women and men, although it has been suggested that not all cases are reported to healthcare systems, therefore making instances appear more rare than they actually are. It affects all ages and all ethnicities, so no age/ethnic group is automatically more at risk. 

Diagnosis 

A diagnosis of ferroportin disease is reached following identification of characterised symptoms of the disease. The patient’s genetic and medical history, a thorough blood examination, clinical evaluation, and a variety of tests will be carried out. 

Genetic testing specifically will be considered before confirmation of the diagnosis and after all other options, such as cancer, alcohol inflammation have been ruled out. Abdominal MRI is especially useful in diagnosing ferroportin disease, particularly as it provides an non-invasive methodology which is preferred by the majority of the general public. The abdominal MRI allows the differentiation of ferroportin disease from the other forms of hereditary hemochromatosis, as ferroportin disease is characterised by accumulation in the spleen, liver, and spine. 

Once a diagnosis of ferroportin disease has been reached, an assessment of organ damage is carried out, as well as analysis of the amount of iron accumulation. 

Symptoms and clinical manifestations

The symptoms of ferroportin disease vary depending on the severity of iron accumulation, type, location. Some common symptoms are fatigue, recurring abdominal pain, reduced sex drive, joint pain, and heart abnormalities. 

The majority of those with ferroportin disease develop it in its mild form, meaning they have lower levels of the protein which carries iron in their blood. Individuals with this type of ferroportin disease can develop mild liver damage as they age. 

As the condition progresses over time some more symptoms can develop:

• Darkening of the skin 
• Yellowing of the skin 
• Frequent thirst and needing to urinate 
• Swelling of the hands and feet 
• Chest pain 

Some individuals develop a rarer type of ferroportin disease which is more similar to hemochromatosis. The symptoms associated with this type include joint pain, abnormalities in the heart rhythm, and diabetes. As this version progresses with age, permanent liver damage and scarring is prevalent. Hypochromic anemia is not uncommon in young menstruating females.

Long term complications 

Ferroportin disease unfortunately comes with the risks of developing some long term conditions as a result of the iron overload in the body. 

The liver has the ability to compensate for the iron toxicity levels for a certain period of time before permanent damage occurs. However, this is not always the case with many individuals who did not receive a proper diagnosis or receiving one later in life. There are also risks of developing diabetes as a result of pancreatic damage, cardiac damage, and osteoporosis. 

In the case of osteoporosis, sometimes symptoms can develop before the age of 30 and sometimes even younger than that. Treatments such as the artificial removal of iron options have not seemed to create any improved symptoms in the individuals. 

Treatment options

Removing excess iron from the body 

There are no natural mechanisms in the body to eradicate excess iron, meaning it must be artificially removed. There are two main ways of going about this - blood removal and iron chelators. 

Blood removal (venesection)

When anaemia is not a symptom then blood removal is considered as the main therapeutic methodology. It is more commonly known in medical environments as venesection or phlebotomy. The procedure is similar to the process of donating blood; as the blood is removed, the red blood cells containing iron are removed,  therefore helping to reduce the amount of iron in blood. 

The frequency of this treatment determines its effect; a regular treatment (usually weekly) is normally done until the iron levels are normal, so treatment overall usually lasts about a year. Following this to maintain the lower iron levels, blood is taken usually 2 to 4 times a year and this is usually required indefinitely. 

Iron chelators

This treatment option is not as commonly used as blood removal as is typically suggested in cases where it is not possible to regularly remove blood, for example if you suffer from very fragile veins. 

This treatment option involves taking a form of medication (sometimes either deferasirox or desferrioxamine) which removes iron from the blood via excretion.

Diet and alcohol

Treatment via dietary changes and the elimination of alcohol is a controversial option and is often suggested in the treatment of hemochromatosis. However it would not be recommended for ferroportin disease as the iron uptake mechanisms are different. 

Psychological and Social Impact

Ferroportin disease is by definition a chronic illness meaning it's not only incredibly impactful on an individual's physical health, but their mental wellbeing too. 

Ferroportin disease, like all chronic illnesses, is a lifelong condition which cannot be completely cured and is rather only treated to ease symptoms. Chronic physical illnesses can be psychologically draining for those experiencing it, with conditions such as anxiety and depression being most common. Some patients often have to adjust or even give up some lifestyle elements to accommodate their illness. It is always recommended that those with chronic illness monitor their mental health and seek assistance if they feel they are struggling to cope. 

There are some self care tips to manage your mental health when physically unwell:

• Talk to those around you about how the illness makes you feel, or local support groups and communities
• Seeking practical help and therapies if needed, having small things like the groceries and chores taken care of can help alleviate stress and anxiety 
• Relaxation and mindfulness
• Sticking to routines and plans as much as possible
• Managing unhelpful thoughts
• Getting a good night's sleep by ensuring good sleep hygiene 
• Resting and keeping a healthy lifestyle 
• Eating well and exercising if able 

It is not uncommon to develop a mental health problem following a long term physical illness diagnosis, with UK statistics showing almost 1 in 3 people with long term physical illness also having some kind of mental health condition.⁴

Getting help 

Those with long-term physical illness should not wait to seek out ways of managing and mining their mental health, as small choices every day can help make a lot of difference. There are many ways to seek help if needed:

• Talking to your doctor about any therapies available, or any support groups they can recommend or sign post you to
• CBT (Cognitive Behavioural Therapy)
• Getting into contact with others living with Ferroportin disease

Summary 

Ferroportin disease is a dominant genetic condition resulting in elevated iron levels in the body. There is no cure for the condition and it is inherited from a parent carrying the gene, meaning families where one person is diagnosed are typically all tested. Symptoms vary among individuals depending on the type and severity of the condition, with many developing lifelong physical complications such as diabetes and heart arrhythmia, as well as mental health complications such as anxiety and depression. 

Living with ferroportin disease does affect to some extent the quality of life, but management of the symptoms over the lifetime can help individuals live as normal a life as possible. As no cure is yet available it is important that research continues to focus on this disease, allowing the possibility of new treatment options.