Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is unclear if it is effective for treating sexual dysfunction in women. It is taken by mouth or by injection into a vein. Onset is typically within twenty minutes and lasts for about two hours.Common side effects include headaches, heartburn, and flushed skin. Caution is advised in those with cardiovascular disease. Rare but serious side effects include a prolonged erection (priapism) that can lead to damage to the penis, vision problems, and hearing loss. Sildenafil should not be taken by people on nitrates such as nitroglycerin (glycerin trinitrate), as this may result in a serious drop in blood pressure. Sildenafil should not be taken within four hours of taking an alpha blocker. Sildenafil acts by blocking phosphodiesterase 5 (PDE5), an enzyme that promotes breakdown of cGMP, which regulates blood flow in the penis. It requires sexual arousal to work. It also results in dilation of the blood vessels in the lungs.Pfizer originally discovered the medication in 1989 while looking for a treatment for heart-related chest pain. It was approved for medical use in the United States and in the European Union in 1998. In 2017, it was the 217th-most commonly prescribed medication in the United States, with more than two million prescriptions. That same year, it also became available as a generic medication after final patents by Pfizer expired. In the United Kingdom, it is available over the counter.
These mutations in the PEX7 gene generally lead to rhizomelic chondrodysplasia punctata type 1- which impairs development of many parts of the body. Refsum disease is inherited in an autosomal recessive pattern, meaning that it requires both copies of the mutation to inherit the disease. Diagnosis
Histopathologic examination of the skin from a suspected patient commonly shows hyperkeratosis, hyper-granulosis and acanthosis. The presence of cells in the basal and suprabasal layers of the epidermis containing variably sized vacuoles with accumulated lipids is pathognomonic for the disease. Classification
Adult Refsum disease may be divided into the adult Refsum disease 1 and adult Refsum disease 2 subtypes. The former stems from mutations in the phytanoyl-CoA hydroxylase (PAHX aka PHYH) gene, on the PHYH locus at 10p13 on chromosome 6q22-24. It was initially believed this was the sole mutation; however 55% of cases are now attributed to mutations in other genes.Refsum disease 2 stems from mutations in the peroxin 7 (PEX7) gene. This mutation on the PEX7 gene is also on chromosome 6q22-24, and was found in patients presenting with accumulation of phytanic acid with no PHYH mutation.Adult Refsum disease should not be confused with infantile Refsum disease, a peroxisome biogenesis disorder resulting from deficiencies in the catabolism of very long chain fatty acids and branched chain fatty acids (such as phytanic acid) and plasmalogen biosynthesis.