Pathogenesis, Diagnosis, and Clinical Implications of Hereditary Hemochromatosis—The Cardiological Point of View

Abstract

Hereditary hemochromatosis (HH) is a genetic disease leading to excessive iron absorption, its accumulation, and oxidative stress induction causing different organ damage, including the heart. The process of cardiac involvement is slow and lasts for years. Cardiac pathology manifests as an impaired diastolic function and cardiac hypertrophy at first and as dilatative cardiomyopathy and heart failure with time. From the moment of heart failure appearance, the prognosis is poor. Therefore, it is crucial to prevent those lesions by upfront therapy at the preclinical phase of the disease. The most useful diagnostic tool for detecting cardiac involvement is echocardiography. However, during an early phase of the disease, when patients do not present severe abnormalities in serum iron parameters and severe symptoms of other organ involvement, heart damage may be overlooked due to the lack of evident signs of cardiac dysfunction. Considerable advancement in echocardiography, with particular attention to speckle tracking echocardiography, allows detecting discrete myocardial abnormalities and planning strategy for further clinical management before the occurrence of substantial heart damage. The review aims to present the current state of knowledge concerning cardiac involvement in HH. In addition, it could help cardiologists and other physicians in their everyday practice with HH patients.

Chronic Fatigue Syndrome in Patients with Deteriorated Iron Metabolism

“…Excess iron levels in the serum may be associated with fatigue; however, it has different pathophysiology than iron deficiency [ 99 , 100 ].…”

“…Increased absorption of dietary iron, frequent transfusions, and ineffective erythropoiesis [ 101 , 102 ], and the most often reason is hereditary hemochromatosis (HH). HH is a genetic disease that increases iron accumulation in body tissues [ 100 ]. Besides HFE-related hemochromatosis, other iron overload mutations are not related to the HFE gene [ 100 ].…”

“…HH is a genetic disease that increases iron accumulation in body tissues [ 100 ]. Besides HFE-related hemochromatosis, other iron overload mutations are not related to the HFE gene [ 100 ].…”

“…The patient should undergo a laboratory diagnosis if iron overload is suspected based on symptoms such as chronic fatigue, dark skin color, arthralgia, or hepatomegaly. If their ferritin level is >200 ng/mL for premenopausal women, >300 ng/mL for men and post-menopausal women, and transferrin saturation level is >45%, the patient should have genetic diagnostics performed to exclude the presence of mutations within the HFE gene ( Figure 1 ) [ 100 ].…”

Diagnostic Modalities in Detecting Cardiovascular Complications of Thalassemia

“…Since this technique is still in development, the measurement technique of 2D or 3D speckle tracking should improve their intervendor reliability. In addition, more studies are required to determine the relevance of early abnormalities and their correlation to treatment and prognosis [36,37].…”