Non-HFE hemochromatosis

Abstract

Hereditary hemochromatosis (HH) is an autosomal recessive disorder classically related to HFE mutations. However, since 1996, it is known that HFE mutations explain about 80% of HH cases, with the remaining around 20% denominated non-HFE hemochromatosis. Nowadays, four main genes are implicated in the pathophysiology of clinical syndromes classified as non-HFE hemochromatosis: hemojuvelin (HJV, type 2Ajuvenile HH), hepcidin (HAMP, type 2B juvenile HH), transferrin receptor 2 (TFR2, type 3 HH) and ferroportin (SLC40A1, type 4 HH). The aim of this review is to explore molecular, clinical and management aspects of non-HFE hemochromatosis.

How should hyperferritinaemia be investigated and managed?

“…Type 2 HH or juvenile haemochromatosis is a rare autosomal recessive disease that has an onset of symptoms between the first to third decades of life, and affects males and females equally. The predominant features are hypogonadotropic hypogonadism and cardiomyopathy, with cardiac involvement being the most common cause of death [26]. Other manifestations include liver fibrosis or cirrhosis, diabetes mellitus and arthropathy [27,28].…”

Autoimmune Hepatitis: Diagnostic Dilemma in the Setting of Suspected Iron Overload

“…In a study performed in Germany of 531 patients, 17.2% of patients diagnosed with AIH had heterozygous C282Y mutation [5]. Moreover, there are other point mutations including H63D and non-HFE gene mutations such as hemojuvelin (HJV), hepcidin (HAMP), transferrin receptor 2 (TfR2), and ferroportin (SLC40A1) that are shown to cause milder degree of iron overload [6]. However, these mutations seem to have variable penetrance with only one in ten individuals with heterozygous mutations having elevated serum iron profile.…”

<b><i>HAMP</i></b> Gene Mutation Associated with Juvenile Hemochromatosis in Brazilian Patients

“…The endocrine and cardiac manifestations, such as hypogonadotropic hypogonadism, amenorrhea, impotence, diabetes and heart failure, as well as severe iron overload, are frequently observed in young patients. Appropriate genetic testing is very important for patients that present the signs and symptoms of JH, considering that an early diagnosis can lead to more adequate and faster treatment - and therefore management - of the disease, thus increasing the patient's quality of life [1,10,11,12,13]. …”

“…This disorder is associated with liver damage, hypogonadotropic hypogonadism, cardiomyopathy and endocrine dysfunctions, leading to organ damage before the age of 30 years in patients of both sexes [1]. …”