As about the people with one copy of the H63D alteration (heterozygous carriers), this genotype is very unlikely to cause a clinical presentation, there is no predictable risk of iron overload. Besides that, two 2020 studies revealed that the frequency of homozygous or heterozygous H63D variant is significantly higher in elite endurance athletes comparing to ethnically matched controls, and is associated with high V̇O2max in male athletes. . Each patient with the susceptible genotype accumulates iron at different rates depending on iron intake, the exact nature of the genetic variant, and the presence of other insults to the liver, such as alcohol and viral disease. As such, the degree to which the liver and other organs are affected is highly variable and is dependent on these factors and co-morbidities, as well as age at which they are studied for manifestations of disease. Penetrance differs between populations. Disease-causing genetic variants of the HFE gene account for 90% of the cases of non-transfusion iron overload.This gene is closely linked to the HLA-A3 locus. Pathophysiology
Since the regulation of iron metabolism is still poorly understood, a clear model of how haemochromatosis operates is still not available. A working model describes the defect in the HFE gene, where a mutation puts the intestinal absorption of iron into overdrive. Normally, HFE facilitates the binding of transferrin, which is irons carrier protein in the blood. Transferrin levels are typically elevated at times of iron depletion (low ferritin stimulates the release of transferrin from the liver).
Kindler syndrome (also known as "bullous acrokeratotic poikiloderma of Kindler and Weary",)  is a rare congenital disease of the skin caused by a mutation in the KIND1 gene. Symptoms and signs
Infants and young children with Kindler syndrome have a tendency to blister with minor trauma and are prone to sunburns. As individuals with Kindler syndrome age, they tend to have fewer problems with blistering and photosensitivity. However, pigment changes and thinning of the skin become more prominent. Kindler syndrome can affect various mucous tissues such as the mouth and eyes, which can lead to other health problems. Genetics
Kindler syndrome is an autosomal recessive genodermatosis. The KIND1 gene mutated in Kindler syndrome codes for the protein kindlin-1, which is thought to be active in the interactions between actin and the extracellular matrix (focal adhesion plaques). Kindler syndrome was first described in 1954 by Theresa Kindler. Diagnosis
Clinical and genetic tests are used to confirm diagnosis. Management
Treatment may involve several different types of practitioner to address the various manifestations that may occur. This multidisciplinary team  will also be involved in preventing secondary complications. See also
Rothmund–Thomson syndrome
Epidermolysis bullosa
List of cutaneous conditions

References


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