Abstract
Juvenile hemochromatosis (JH), type 2A hemochromatosis, is a rare autosomal recessive disorder of systemic iron overload due to homozygous mutations of HJV (HFE2), which encodes hemojuvelin, an essential regulator of the hepcidin expression, causing liver fibrosis, diabetes, and heart failure before 30 years of age, often with fatal outcomes. We report two Japanese sisters of 37 and 52 years of age, with JH, who showed the same homozygous HJV I281T mutation and hepcidin deficiency and who both responded well to phlebotomy on an outpatient basis. When all reported cases of JH with homozygous HJV mutations in the relevant literature were reviewed, we found—for the first time—that JH developed in females and males at a ratio of 3:2, with no age difference in the two groups. Furthermore, we found that the age of onset of JH may depend on the types of HJV mutations. In comparison to patients with the most common G320V/G320V mutation, JH developed earlier in patients with L101P/L101P or R385X/R385X mutations and later in patients with I281T/I281T mutations.
Highlights
Hereditary hemochromatosis is a rare disorder of systemic iron overload due to deficiency of hepcidin, leading to intestinal iron hyperabsorption, and occurs in an autosomal recessive manner except for autosomal dominant type 4 hemochromatosis [1,2,3,4]
Unlike other hereditary hemochromatosis—which mostly occurs in individuals of >30 years of age, rarer subtypes of HJV-related type 2A and HAMP-related type 2B hemochromatosis, which usually develop in the first to third decades of life—causes severe clinical complications, such as liver fibrosis, hepatocellular carcinoma, diabetes, hypogonadism, and heart failure; HJV-related type 2A hemochromatosis is referred to as juvenile hemochromatosis (JH) [1,5]
The patient’s laboratory findings showed high levels of transferrin saturation (93%), serum ferritin (2274 ng/mL) and alanine aminotransferase (51 U/L; reference range, 5–40), insulin-dependent diabetes, iron deposition of the anterior pituitary gland on nuclear magnetic resonance (NMR), with hypogonadism, and massive iron deposition in hepatocytes observed in a liver biopsy (Table 1)
Summary
Hereditary hemochromatosis is a rare disorder of systemic iron overload due to deficiency of hepcidin, leading to intestinal iron hyperabsorption, and occurs in an autosomal recessive manner except for autosomal dominant type 4 hemochromatosis [1,2,3,4]. Unlike other hereditary hemochromatosis—which mostly occurs in individuals of >30 years of age, rarer subtypes of HJV-related type 2A and HAMP (encoding hepcidin)-related type 2B hemochromatosis, which usually develop in the first to third decades of life—causes severe clinical complications, such as liver fibrosis, hepatocellular carcinoma, diabetes, hypogonadism, and heart failure; HJV-related type 2A hemochromatosis is referred to as juvenile hemochromatosis (JH) [1,5]. The first line of therapy in hemochromatosis is iron removal by phlebotomy to prevent the progression of organ damage due to iron overload [4]. In order to develop safe and effective treatments for JH, it is important to better understand its clinical features
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