The “Celtic Curse” is an informal name for Hereditary Hemochromatosis (HH), a genetic disorder causing the body to absorb and store too much iron from the diet. This results in a progressive iron overload that can eventually damage various organs and tissues. The excess iron accumulates because the body lacks an effective mechanism to excrete the surplus metal. HH is one of the most common genetic disorders in people of Northern European descent.
The Genetic Origin of Hereditary Hemochromatosis
Hereditary Hemochromatosis is an autosomal recessive disorder, meaning a person must inherit a faulty copy of the gene from both parents. The majority of cases are linked to mutations in the HFE gene, which is located on chromosome 6. The two most common mutations are C282Y and H63D, with C282Y homozygosity (inheriting two copies of the C282Y mutation) being the most frequent cause of clinical iron overload.
The nickname “Celtic Curse” stems from the disorder’s high prevalence in populations with Irish, Scottish, Welsh, and other Northern European ancestry. The C282Y mutation is particularly common in these populations, with estimates suggesting that as many as one in 10 people in Northern Ireland may be at risk. This genetic variation is thought to have provided an evolutionary advantage in ancient populations with iron-poor diets.
How Iron Overload Affects the Body
The HFE gene provides instructions for making a protein that helps regulate the iron-controlling hormone hepcidin. In people with the condition, the faulty HFE protein leads to inappropriately low levels of hepcidin. Hepcidin normally acts as a brake on iron absorption and release, so its deficiency causes the digestive tract to absorb an excessive amount of iron from food.
The body continuously takes in iron even when its stores are full, leading to an iron overload. This excess iron is then deposited in various organs, a process called hemosiderosis. The iron accumulates as a storage protein called ferritin, and when the transferrin that normally transports iron becomes saturated, the free iron can become toxic.
The deposited iron causes damage by generating reactive oxygen species, leading to inflammation and scarring (fibrosis or cirrhosis) in the affected organs. These vulnerable organs include the liver, heart, pancreas, joints, and pituitary gland. Liver damage is a primary concern, as chronic iron accumulation can lead to cirrhosis and an increased risk of liver cancer.
Recognizing the Signs and Getting Diagnosed
The symptoms of Hereditary Hemochromatosis are often non-specific. Early signs are vague, including chronic fatigue and joint pain. Symptoms typically appear later in life, usually after age 40 in men and after menopause in women, due to the protective effect of menstrual blood loss.
As iron deposition progresses, more specific signs emerge. These can include abdominal pain, heart rhythm abnormalities or heart failure from cardiac iron deposits, and diabetes mellitus from iron damage to the pancreas. A characteristic sign is skin bronzing or hyperpigmentation, sometimes called “bronze diabetes.”
Diagnosis begins with blood tests that measure iron levels. The two primary screening tests are serum ferritin, which measures stored iron, and transferrin saturation, which indicates circulating iron. Elevated levels in these tests prompt further investigation, which is definitively confirmed by genetic testing for the HFE gene mutations, specifically C282Y and H63D.
Treatment and Management Options
The primary and most effective treatment for managing iron overload in Hereditary Hemochromatosis is therapeutic phlebotomy, the controlled removal of blood. Since iron is primarily contained within red blood cells, this process effectively removes excess iron from the body.
The treatment occurs in two phases: an initial, intensive phase where blood is removed frequently, often weekly, until iron levels are brought down to a safe range. This is followed by a maintenance phase, where blood is removed less often, typically every two to four months, to keep iron levels normalized. Early diagnosis and phlebotomy can prevent most organ damage and greatly improve life expectancy.
For individuals who cannot tolerate regular phlebotomy due to poor venous access or certain health conditions, iron chelation therapy is an alternative. This involves taking medication that binds to the excess iron in the blood, allowing the body to excrete it through urine or stool. Patients are also advised to avoid iron supplements and high-dose vitamin C, which increases iron absorption, as part of their long-term management plan.