From the Guidelines
Hereditary Hemochromatosis (HH) is a genetic disorder characterized by increased intestinal iron absorption and iron release from macrophages, leading to progressive body iron accumulation, mainly in the liver, and can result in liver fibrosis, cirrhosis, and hepatocellular carcinoma if left untreated. According to the most recent and highest quality study 1, haemochromatosis is an autosomal recessive condition characterized by elevated transferrin saturation (TSAT) and progressive iron loading that mainly affects the liver. The study also states that early diagnosis and treatment by phlebotomy can prevent cirrhosis, hepatocellular carcinoma, diabetes, arthropathy, and other complications.
Key Characteristics of Hereditary Hemochromatosis
- Increased transferrin saturation (TSAT) and progressive iron loading
- Mainly affects the liver
- Can result in liver fibrosis, cirrhosis, and hepatocellular carcinoma if left untreated
- Autosomal recessive condition, most commonly caused by mutations in the HFE gene
Diagnosis and Treatment
- Provisional iron overload based on serum iron parameters (TSAT >45% and ferritin >200 µg/L in females and TSAT >50% and ferritin >300 µg/L in males and post-menopausal women) is sufficient to diagnose haemochromatosis in patients homozygous for p.Cys282Tyr in HFE 1
- Treatment targets for phlebotomy are ferritin <50 µg/L during the induction phase and <100 µg/L during the maintenance phase 1
- Regular monitoring of iron levels through ferritin and transferrin saturation tests is essential
Prevention of Complications
- Early treatment can prevent complications like liver cirrhosis, diabetes, heart problems, and arthritis
- Family screening is recommended for first-degree relatives, as hemochromatosis is autosomal recessive and most commonly caused by mutations in the HFE gene 1
From the Research
Definition and Characteristics of Hereditary Hemochromatosis (HH)
- Hereditary Hemochromatosis (HH) is a genetic disorder that affects iron hemostasis, resulting in increased transferrin saturation, hyperferritinemia, and parenchymal iron overload 2.
- It is characterized by an inappropriate increase in intestinal iron absorption due to reduced expression of the iron regulatory protein, hepcidin 3.
- The disease is most commonly due to the autosomal recessive inheritance of a C282Y substitution in the HFE protein, whereby both alleles of the corresponding gene are affected 3.
Clinical Manifestations and Diagnosis
- Progressive iron deposition in parenchymal tissues may ultimately lead to liver and other organ toxicity 3.
- The characteristic biochemical abnormalities are raised serum ferritin and transferrin saturation, which can be used in conjunction with genetic tests and emerging magnetic resonance imaging-based techniques to diagnose patients with the disorder 3.
- Diagnosis is crucial to distinguish HH from other causes of hyperferritinemia, which is a common finding in patients with metabolic disorders 2.
Treatment and Management
- Treatment with phlebotomy remains the first-line therapy, and if instigated early, leads to a normal life expectancy 3, 4.
- Phlebotomy is effective in reducing mean ferritin concentration and transferrin saturation 5.
- A healthy, well-balanced diet is recommended to be incorporated as part of the ongoing management of the disease 3.
- Lifestyle changes are important for management, and genetic and lifestyle cofactors (especially alcohol and dysmetabolic features) significantly modulate clinical expression 4.