What does homozygous for H63D mean?

What does homozygous for H63D mean?

The homozygous H63D variant is an indicator of the iron metabolism disorder hemochromatosis, which may increase the risk of developing a fatty liver. In patients with a cirrhotic liver, the mutation can increase the rate of liver cancer.

How rare is H63D mutation?

Within the Caucasian population of this group, 0.44% were homozygous for the C282Y mutation and 2.4% were homozygous for the H63D mutation (18).

Does H63D cause hemochromatosis?

Compound heterozygous C282Y/H63D have a four-fold increased risk of hemochromatosis as compared with the general population. Homozygous genotype H63D/H63D is not associated with increased iron deposition. First-degree relatives of patients with HH should be screened for the disease.

What is C282Y?

The second mutation introduces a missense mutation (C282Y) into the Hfe locus, but otherwise leaves the gene intact. This mutation is identical to the disease-causing mutation in patients with hereditary hemochromatosis. Mice carrying each of the two mutations were bred and analyzed.

What happens if you are a carrier of haemochromatosis?

If left untreated , haemochromatosis can lead to arthritis, liver damage, and premature death. As it is an inherited disorder, people with hereditary haemochromatosis carry two faulty genes – one from each parent. A person with one faulty gene is a ‘carrier’ and won’t develop the condition themselves.

Is C282Y an allele?

The C282Y allele is the major cause of hemochromatosis as a result of excessive iron absorption. The mutation arose in continental Europe no earlier than 6,000 years ago, coinciding with the arrival of the Neolithic agricultural revolution.

How common is it to be a carrier for hemochromatosis?

As it is an inherited disorder, people with hereditary haemochromatosis carry two faulty genes – one from each parent. A person with one faulty gene is a ‘carrier’ and won’t develop the condition themselves. One in seven people carry the condition, and it is equally likely in men and women.

What is the pathophysiology of homozygous H63D?

Homozygousity for H63D is an insufficient genetic explanation for iron overload. When homozygousity of H63D is seen in association with raised iron or transferrin saturation, co-morbid factors are usually present.

How common is iron overload in H63D homozygotes?

The majority of H63D homozygotes (85.1%) had no evidence of iron overload. Three (3.2%) had documented iron overload, with one (1.1%) meeting criteria for iron overload-related disease. Eleven (11.7%) had provisional iron overload. Sixty individuals had follow-up data available and, of these, four (6.7%) had documented iron overload.

What is the prognosis of HFE compound homozygotes (H63D/H63D)?

The risk of HH related morbidity in HFE compound homozygotes patients (H63D /H63D) is considered rare, we report a male patient with H63D mutation who developed impaired glucose tolerance, and high hepatic enzymes due to significant iron accumulation in the liver as well as Parkinsonian-like syndrome due to iron deposition in the basal ganglia.

How many hemochromatosis patients are homozygous for the H63D mutation?

One study found that three of 61 individuals with a phenotypic diagnosis of hemochromatosis were homozygous for the H63D mutation (5). These patients had either a hepatic iron index >1.9 or mobilizable iron stores of >4 g.