Which are the causes of Sjögren-Larsson Syndrome?

Sjögren-Larsson Syndrome (SLS) is a rare genetic disorder that affects multiple systems in the body. It is characterized by a triad of symptoms including ichthyosis (a skin condition), intellectual disability, and spasticity (muscle stiffness). The syndrome was first described by Swedish dermatologists Sven Gustaf Sjögren and Tage Larsson in 1957.

The primary cause of Sjögren-Larsson Syndrome is a mutation in the ALDH3A2 gene, which is responsible for producing an enzyme called fatty aldehyde dehydrogenase (FALDH). This enzyme plays a crucial role in the breakdown of long-chain fatty alcohols and fatty aldehydes. The mutation in the ALDH3A2 gene leads to a deficiency or complete absence of FALDH, resulting in the accumulation of fatty aldehydes in the body.

Fatty aldehydes are toxic to cells and disrupt normal cellular processes. Their accumulation in various tissues, including the skin, brain, and spinal cord, leads to the characteristic symptoms of Sjögren-Larsson Syndrome.

The exact mechanism by which the ALDH3A2 gene mutation causes the specific symptoms of SLS is not fully understood. However, it is believed that the accumulation of fatty aldehydes in the skin leads to the development of ichthyosis, which is characterized by dry, scaly, and thickened skin. The impaired barrier function of the skin in SLS patients makes it more susceptible to infections and other complications.

The accumulation of fatty aldehydes in the brain and spinal cord is thought to contribute to the intellectual disability and spasticity seen in Sjögren-Larsson Syndrome. The exact mechanisms by which fatty aldehydes affect brain development and function are still being investigated, but it is believed that they disrupt the normal growth and connectivity of neurons, leading to cognitive impairment and motor dysfunction.

Sjögren-Larsson Syndrome follows an autosomal recessive pattern of inheritance. This means that an individual must inherit two copies of the mutated ALDH3A2 gene (one from each parent) to develop the syndrome. If both parents are carriers of the mutated gene, each child has a 25% chance of being affected by SLS.

In conclusion, Sjögren-Larsson Syndrome is caused by a mutation in the ALDH3A2 gene, leading to a deficiency of the FALDH enzyme and the accumulation of fatty aldehydes in various tissues. This accumulation disrupts normal cellular processes, resulting in the characteristic symptoms of ichthyosis, intellectual disability, and spasticity. Ongoing research aims to further understand the underlying mechanisms of the syndrome and develop potential treatments.