Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung disease, and kidney disease.TSC is caused by a mutation of either of two genes, TSC1 and TSC2, which code for the proteins hamartin and tuberin, respectively, with TSC2 mutations accounting for the majority and tending to cause more severe symptoms. These proteins act as tumor growth suppressors, agents that regulate cell proliferation and differentiation.Prognosis is highly variable and depends on the symptoms, but life expectancy is normal for many.The prevalence of the disease is estimated to be 7 to 12 in 100,000. The disease is often abbreviated to tuberous sclerosis, which refers to the hard swellings in the brains of patients, first described by French neurologist Désiré-Magloire Bourneville in 1880. Signs and symptoms
The physical manifestations of TSC are due to the formation of hamartia (malformed tissue such as the cortical tubers), hamartomas (benign growths such as facial angiofibroma and subependymal nodules), and very rarely, cancerous hamartoblastomas. The effect of these on the brain leads to neurological symptoms such as seizures, intellectual disability, developmental delay, and behavioral problems.
Presentation
Pyrazinamide is a generic drug, and is available in a wide variety of presentations. Pyrazinamide tablets form the bulkiest part of the standard tuberculosis treatment regimen. Pyrazinamide tablets are so large, some people find them impossible to swallow: pyrazinamide syrup is an option. Pyrazinamide is also available as part of fixed-dose combinations with other TB drugs such as isoniazid and rifampicin (Rifater is an example). History
Pyrazinamide was first discovered and patented in 1936, but not used against tuberculosis until 1952. Its discovery as an antitubercular agent was remarkable since it has no activity against tuberculosis in vitro, due to not being active at a neutral pH, so would ordinarily not be expected to work in vivo. However, nicotinamide was known to have activity against tuberculosis and pyrazinamide was thought to have a similar effect. Experiments in mice at Lederle and Merck confirmed its ability to kill tuberculosis and it was rapidly used in humans. References
External links
"Pyrazinamide". Drug Information Portal. U.S. National Library of Medicine.