Hereditary haemochromatosis
Haemochromatosis is a built-in error in the way the body keeps count of iron. The gut takes more of it out of food than is needed, and the surplus has…
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Haemochromatosis is a built-in error in the way the body keeps count of iron. The gut takes more of it out of food than is needed, and the surplus has nowhere to go: the human body has no mechanism at all for throwing spare iron out. Year after year it settles in the liver, the pancreas, the heart, the joints and the pituitary. For the first twenty or thirty years nothing is felt; then comes a tiredness that gets blamed on work and age. What makes the condition dangerous is not its severity but its quietness: found in time, it barely affects how a person feels or how long they live.
Why iron never finds a way out
A person loses roughly a milligram of iron a day, in the cells shed from skin and gut, and women lose more with menstruation. There is no active route out: the kidney does not filter iron and the liver does not burn it. The only adjustable tap is absorption in the duodenum, and it is controlled by a liver hormone, hepcidin. When stores are full there is plenty of hepcidin, it shuts the transport protein in the gut wall, and the iron simply passes through.
In haemochromatosis the signal by which the liver gauges its stores is broken. Hepcidin stays low even with the warehouses overflowing, and instead of a milligram a day three or four enter the bloodstream. The difference looks trivial, yet over thirty years it adds up to tens of grams when the normal store is three or four. The capacity of the proteins that hold iron safely runs out, free iron appears in the blood, and it behaves as an oxidant: it damages cells and sets scarring in motion.
Who inherits it and why not everyone falls ill
In most cases the culprit is the HFE gene, or more precisely one common variant of it. Inheritance is recessive: to be at risk you have to receive a faulty copy from both parents. With a single copy a person is healthy, a carrier, and can pass the change to their children. For a couple who are both carriers, each child has a one in four chance of getting both copies, a one in two chance of being a carrier, and the same one in four of inheriting nothing.
Two copies are not a verdict but a predisposition: full-blown disease develops in a minority, while in the rest iron sits slightly above normal for a lifetime and spoils nothing. Men have the harder time of it, and the course is made considerably worse by alcohol, fatty liver and viral hepatitis, which add to the overload and speed up scarring. Women are protected for decades by menstruation and pregnancies, so the illness shows up later, after the menopause, and more mildly. The variant is common among people of northern European descent, but it is not confined to one region.
There is also a rare form unconnected with HFE. Juvenile haemochromatosis, in which other links in the same hepcidin system fail, loads iron several times faster and announces itself in the early twenties: periods stop, sexual development is delayed, and severe arrhythmia and heart failure appear. It is the form most often missed, because at that age nobody thinks about iron.
If someone in the family has been diagnosed, parents, brothers, sisters and adult children are worth testing even if they feel entirely well. This is one of the few situations in which looking for a disease in people without symptoms is justified without reservation.
The first signs, which get blamed on age
The onset is vague and does not look like illness at all. Usually it amounts to:
- tiredness that rest does not lift, the commonest complaint and the least useful for diagnosis;
- pain in the finger joints, typically at the base of the index and middle fingers, with morning stiffness and a painful handshake;
- loss of sexual desire, erection problems in men, disrupted or absent periods in women before the menopause;
- brain fog, irritability, low mood;
- weight loss and muscle weakness;
- pain under the right ribs, or an enlarged liver found on a scan done for something else.
The famous bronze darkening of the skin and diabetes are late signs, belonging to the stage where organs are already damaged. There is no need to wait for them: nowadays the diagnosis usually arrives long before, by chance, on a blood test. First symptoms most often fall between the ages of thirty and sixty.
What iron does to the organs
The liver takes the main blow: years of overload produce fibrosis and then cirrhosis. Cirrhosis here is doubly dangerous, because it sharply raises the risk of liver cancer and that risk persists even after the iron has been cleared, which is why such patients are kept under regular ultrasound surveillance.
The pancreas. Iron ruins the cells that make insulin, and diabetes follows. Together with darkened skin it gave rise to the old name "bronze diabetes".
The heart. Iron in the heart muscle leads to cardiomyopathy, rhythm disturbances and heart failure: breathlessness, swollen legs, palpitations. In early-onset forms it is the leading cause of death and, at the same time, what responds best to treatment.
The pituitary. Overloaded, it stops instructing the sex glands: hence loss of libido, erectile dysfunction, early cessation of periods, loss of muscle and osteoporosis.
The joints. The arthropathy has a character of its own: it strikes fingers, wrists, hips and knees, and calcium salts settle in the cartilage. It is the one complication that usually does not improve once the iron is removed.
Tiredness, skin colour and the state of the liver and the heart improve on treatment, sometimes strikingly. Cirrhosis, diabetes and joints rarely return to normal — and that is the whole point of looking early.
The tests that settle it
Diagnosis is cheap and rests on two fasting blood tests. Transferrin saturation shows what share of the transport protein is occupied by iron; it rises before any other measure and is therefore the one to search with, and values from around forty-five per cent upwards need explaining. Ferritin reflects the size of the store, is read alongside the first rather than on its own, and is always repeated.
If both are raised, genetic testing for the common HFE variants follows. Then the liver is assessed: blood chemistry, elastography and, where ferritin is high, an MRI scan that measures iron in the liver and the heart without any needle. Biopsy is rarely needed today, mostly to pin down the degree of scarring.
Other reasons for a high ferritin
A raised ferritin on its own does not mean haemochromatosis, and that is the commonest mistake in reading blood results: ferritin is an acute-phase protein and climbs with any inflammation. Far more often than an inherited fault, a high figure comes from:
- fatty liver disease, excess weight, metabolic syndrome — these days the leading cause;
- regular alcohol intake;
- any infection, autoimmune disease, recent surgery or tumour;
- chronic liver disease, including viral hepatitis;
- repeated transfusions for thalassaemia, sickle cell disease or long-term dialysis: the overload here is genuine, but the cause is acquired;
- taking iron on one's own initiative without a confirmed deficiency.
Transferrin saturation separates them: with inflammation or fatty liver it is usually normal, with true overload it is high. A lone ferritin result is therefore a reason to investigate, not a reason to start bleeding someone.
How the excess iron is taken out
The gene cannot be corrected, but what it has accumulated can be removed, and that makes haemochromatosis one of the most rewarding conditions in medicine.
Venesection. The procedure is much like an ordinary blood donation: about half a litre from a vein in the arm. Iron leaves with the red cells, and the bone marrow, building replacements, pulls more of it out of the stores. First comes an intensive phase, roughly weekly, until the store falls to the lower end of normal; that takes anything from a few months to a couple of years. Then maintenance: a handful of sessions a year for life, with blood counts watched so that the person is not left anaemic. In many countries these withdrawals can be combined with ordinary blood donation.
Erythrocytapheresis is a variant in which a machine removes only the red cells and returns the plasma: fewer sessions are needed, but it is not available everywhere.
Chelating drugs bind iron and carry it out in urine and stool. They are needed when venesection is impossible: marked anaemia, serious heart disease, poor veins. The main agents in the group are deferasirox by mouth and desferrioxamine, given under the skin or into a vein. Both require monitoring of kidneys, liver, hearing and eyesight, so they are prescribed by a specialist.
Food, supplements and alcohol
A strict diet is neither necessary nor effective: it is impossible to strip enough iron out of meals to replace the procedures, and attempts end in a meagre plate. The sensible restrictions are few.
- No iron preparations and no supplements containing iron, unless a doctor has specifically prescribed them.
- No large doses of ascorbic acid in tablet form: it increases iron absorption and frees iron from its bound state. Fruit and vegetables can be eaten without worry.
- Alcohol matters most. It damages the liver in its own right and increases iron absorption as well. With established cirrhosis it is given up altogether.
- Raw oysters, mussels and other raw shellfish are off the menu. Seawater harbours the bacterium Vibrio vulnificus, which needs surplus iron to grow. In a person with overload it causes fulminant blood poisoning with very high mortality, whereas a healthy person would get away with an upset stomach.
- Tea and coffee with meals slightly reduce iron uptake; red meat every day increases it.
Online consultation
An online appointment is convenient at exactly the stage where most time gets lost. The doctor can go through the results, explain what ferritin and transferrin saturation mean when read together, and advise whether genetic testing is due or whether the far commoner causes of a high ferritin should be excluded first. They can make sense of years of unexplained tiredness and of pain in the finger joints, and help set out a plan for assessing the liver and the heart. A separate reason to get in touch is a recent diagnosis in a parent or a sibling: at that point the conversation is about you too, however well you feel.
This material is for information only and does not replace medical advice.
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