Which are the causes of Hyperferritinemia Cataract Syndrome?

Hyperferritinemia Cataract Syndrome (HCS) is a rare genetic disorder characterized by the presence of high levels of ferritin in the blood, leading to the development of cataracts. Ferritin is a protein that stores iron in the body, and its levels are tightly regulated to maintain iron homeostasis. When ferritin levels become elevated, it can have detrimental effects on various organs, including the lens of the eye.

1. Genetic Mutations: HCS is primarily caused by mutations in the ferritin light chain (FTL) gene. These mutations disrupt the normal function of ferritin, leading to an abnormal accumulation of iron within the lens of the eye. The exact mechanism by which these mutations cause cataracts is not fully understood, but it is believed to involve oxidative stress and damage to lens proteins.

2. Inherited Disorder: HCS follows an autosomal dominant pattern of inheritance, which means that an affected individual has a 50% chance of passing the mutated gene to their offspring. In some cases, the syndrome can also occur sporadically, without a family history of the disorder.

3. Iron Overload: Elevated ferritin levels in HCS result from iron overload in the body. Iron overload can occur due to various factors, including excessive dietary iron intake, impaired iron metabolism, or underlying conditions such as hereditary hemochromatosis. The excess iron gets deposited in different tissues, including the lens of the eye, leading to the development of cataracts.

4. Oxidative Stress: The accumulation of iron within the lens can promote the production of reactive oxygen species (ROS) through Fenton reactions. ROS are highly reactive molecules that can cause oxidative damage to cellular components, including lens proteins. This oxidative stress contributes to the development of cataracts in individuals with HCS.

5. Age of Onset: HCS typically manifests in adulthood, usually between the ages of 40 and 60. However, the age of onset can vary among affected individuals, and some cases may present earlier or later in life.

Diagnosis of HCS involves clinical evaluation, genetic testing to identify FTL gene mutations, and measurement of ferritin levels in the blood. Treatment options for HCS are limited, and management primarily focuses on cataract surgery to improve vision. Regular monitoring of ferritin levels and iron status is also recommended to prevent complications associated with iron overload.