[22] Finally, a homozygous splice site mutation, IVS5+1 G>A, was reported in a Vietnamese family with HH.[23] This mutation, which causes skipping

of exon 5, has been reported with low frequency in the Vietnamese population (0.3% allele frequency[24]) as well as in Thailand.[25] Interestingly, the same mutation has been found in the Vietnamese population residing in the USA but with a much higher allele frequency of around 2%.[26] In spite of this frequency, only two homozygous individuals KU-60019 supplier have been reported, one of whom had iron overload, while the other did not, suggesting variable penetrance of this mutation similar to that seen for C282Y.[26] Juvenile hemochromatosis (JH) is the most severe form of HH, with symptomatic onset usually occurring within the first three decades of life. JH can arise from germline mutations in one of two genes, hemojuvelin (HJV) that accounts for approximately 90% of JH cases and is termed type 2a HH, or hepcidin that accounts for the remainder and is termed type 2b HH. In both disorders,

inheritance is autosomal recessive, and definitive diagnosis Selumetinib cell line is only achieved via gene sequencing. Patients with JH typically present in their teenage years or 20s with symptoms that may include hypogonadotropic hypogonadism or associated reproductive problems, and/or cardiomyopathy.[27] Apart from the early age of onset, another feature of JH that differentiates it from HFE-HH is that clinically, males and females are affected in equal proportions.

Biochemical testing of these patients reveals elevations in both serum ferritin (typically over 1000 μg/L) and transferrin saturation (typically 80–100%). Other clinical features that may be present include arthropathy, diabetes mellitus, and liver fibrosis or cirrhosis. In a study of 29 patients with the disorder, characteristics of hypogonadism or cardiomyopathy were present in 96% and 35%, respectively.[27] It is these features of JH that contribute mainly to the associated morbidity and mortality. If not detected selleck chemical and treated in the early stages of symptomatic presentation, cardiac failure becomes a leading cause of death in this group. If identified early, however, effective treatment can significantly limit the progression of these symptoms and minimize morbidity and mortality. The treatment of JH typical requires initial aggressive phlebotomy to reduce accumulated iron stores, followed by phlebotomy guided by monitoring to maintain normal iron parameters; treatment is the same for both types 2a and 2b JH. Iron chelators may also be used to rapidly reduce iron stores, especially in those patients with cardiomyopathy where phlebotomy therapy may not be suitable. The gene for type 2a HH was originally mapped by linkage analysis to chromosome 1q.