Disruption of CGI-58 gives rise to the symptoms of ichthyosis, a dermatological condition in which skin becomes very scaly, thick and dry.Ichthyosis is an inherited disorder, like NLSD, and has been found to be genetically linked in some situations with the PNPLA2 gene. Therefore, sometimes when there is a mutation in the PNPLA2 gene, the linked allele of CG-58 is mutated as well. This specific gene, however, does not produce ichthyosis on its own. Ichthyosis can be diagnosed individually in a patient and the genetic cause for unlinked ichthyosis is different from the gene linked with PNPLA2. Keep in mind these disorders may occur individually within a patient as well. Pathophysiology
The functional changes that occur with this disease are mostly metabolic. Accumulation of triglycerides in the body without an efficient mode for catabolism is thought to lead to the eventual symptoms of this disease. Upon digestion and absorption of fat by the small intestine, triglycerides are combined with vitamins and cholesterol to form chylomicrons. Chylomicrons travel from the intestine into the lymph system before entering the bloodstream. Enzymatic catalysis of chylomicrons by lipases in the bloodstream enables the uptake of lipids and fatty acids by cells. In individuals with NLSD, their triglycerides are not catabolized in the blood, and cells accumulate partially processed lipid droplets over time, which may lead to dysfunction in absorbing tissues. In affected individuals, muscle cells, fibroblasts, and leukocytes appear to be prone to the excessive accumulation of triglycerides as lipid droplets.
People can live with NLSD, but there can be complications due to the affects this disease has on other major parts of the body like the liver, the heart, and skeletal muscle. Whereas myopathy won’t necessarily show up until a patient is in the third decade of their life, a child born with ichthyosis, is immediately evaluated for NLSD, in which it is detected very early on. Also, the earlier that NLSD can be detected and symptoms treated, the better quality of life the patient can have. Treatment
Although there is no current treatment to correct the abnormal metabolic processes underlying this disease, there are approaches to ameliorate symptoms and decrease the effects of this disease. Because there is an increase of fat storage and a decrease in fat catabolism, low fat diets are recommended for slowing the progression of the disease, including the onset of type 2 diabetes and hypothyroidism. In addition, diets containing triglycerides composed of short chain fatty acids are more beneficial than TGAs containing long chain fatty acids. Ketone bodies can be rapidly transported, catabolized, and used by many tissues including the brain. Medium-chain fatty acids in an individual’s diet are rapidly used by the body, limiting storage and therefore alleviating lipid droplet accumulation. Foods with medium-chain fatty acids include dairy, fat and coconut oil. Supplements can also be taken to increase uptake of these fatty acids. Triaheptanoin, a triglyceride containing three seven-carbon chain fatty acids, has also been proposed as a possible dietary supplement.