Lesch–Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This deficiency occurs due to mutations in the HPRT1 gene located on the X chromosome. LNS affects about 1 in 380,000 live births. The disorder was first recognized and clinically characterized by American medical student Michael Lesch and his mentor, pediatrician William Nyhan, at Johns Hopkins.The HGPRT deficiency causes a build-up of uric acid in all body fluids. The combination of increased synthesis and decreased utilization of purines leads to high levels of uric acid production. This results in both high levels of uric acid in the blood and urine, associated with severe gout and kidney problems. Neurological signs include poor muscle control and moderate intellectual disability. These complications usually appear in the first year of life. Beginning in the second year of life, a particularly striking feature of LNS is self-mutilating behaviors, characterized by lip and finger biting. Neurological symptoms include facial grimacing, involuntary writhing, and repetitive movements of the arms and legs similar to those seen in Huntingtons disease. The cause of the neurological abnormalities remains unknown. Because a lack of HGPRT causes the body to poorly utilize vitamin B12, some males may develop megaloblastic anemia.LNS is inherited in an X-linked recessive manner; the gene mutation is usually carried by the mother and passed on to her son, although one-third of all cases arise de novo (from new mutations) and do not have a family history. LNS is present at birth in baby boys.
Nabilone, sold under the brand name Cesamet among others, is a synthetic cannabinoid with therapeutic use as an antiemetic and as an adjunct analgesic for neuropathic pain. It mimics tetrahydrocannabinol (THC), the primary psychoactive compound found naturally occurring in Cannabis.The Food and Drug Administration in the United States has indicated nabilone for chemotherapy-induced nausea/vomiting. In other countries, such as Canada, it is widely used as an adjunct therapy for chronic pain management. Numerous trials and case studies have demonstrated modest effectiveness for relieving fibromyalgia and multiple sclerosis. Medical uses
Nabilone is used to treat nausea and vomiting in people under chemotherapy.Nabilone has shown modest effectiveness in relieving fibromyalgia. A 2011 systematic review of cannabinoids for chronic pain determined there was evidence of safety and modest efficacy for some conditions.The main settings that have seen published clinical trials of nabilone include movement disorders such as parkinsonism, chronic pain, dystonia and spasticity neurological disorders, multiple sclerosis, and the nausea of cancer chemotherapy. Nabilone is also effective in the treatment of inflammatory bowel disease, especially ulcerative colitis. In one study of current daily users of cannabis, oral nabilone at 4, 6, and 8 mg produced sustained and dose-dependent mood elevation and psychomotor slowing comparable to 10 or 20 mg oral dronabinol (THC). Nabilone had a slower onset of peak action and a greater dose-dependence of effects, which the investigators attributed to greater bioavailability.