The GM2 gangliosidoses are a group of three related genetic disorders that result from a deficiency of the enzyme beta-hexosaminidase. This enzyme catalyzes the biodegradation of fatty acid derivatives known as gangliosides. The diseases are better known by their individual names: Tay–Sachs disease, AB variant, and Sandhoff disease. Beta-hexosaminidase is a vital hydrolytic enzyme, found in the lysosomes, that breaks down lipids. When beta-hexosaminidase is no longer functioning properly, the lipids accumulate in the nervous tissue of the brain and cause problems. Gangliosides are made and biodegraded rapidly in early life as the brain develops. Except in some rare, late-onset forms, the GM2 gangliosidoses are fatal.All three disorders are rare in the general population. Tay–Sachs disease has become famous as a public health model because an enzyme assay test for TSD was discovered and developed in the late 1960s and early 1970s, providing one of the first "mass screening" tools in medical genetics. It became a research and public health model for understanding and preventing all autosomal genetic disorders.Tay–Sachs disease, AB variant, and Sandhoff disease might easily have been defined together as a single disease, because the three disorders are associated with failure of the same metabolic pathway and have the same outcome. Classification and naming for many genetic disorders reflects history, because most diseases were first observed and classified based on biochemistry and pathophysiology before genetic diagnosis was available. However, the three GM2 gangliosidoses were discovered and named separately.
Barring any disturbances to the cocoon, an adult flea will emerge from the puparium after 9–15 days.In the adult phase, the flea will occasionally feed on unsuspecting animals. Only once the female burrows into the skin can reproduction occur, as the male and female show no interest in each other in the wild. The male flea dies after copulation. The female flea continues in vivo ectodevelopment, described in stages by the Fortaleza classification of tungiasis. Fortaleza classification
In a seminal paper on the biology and pathology of Tunga penetrans, Eisele et al. (2003) provided and detailed the five stages of tungiasis, thereby detailing the in vivo development of the female chigoe flea for the first time. In dividing the natural history of the disease, the Fortaleza Classification formally describes the last part of the female fleas life cycle where it burrows into its hosts skin, expels eggs, and dies. Due to the nature of the discussion, overlap with other sections, particularly the one on symptoms, is unavoidable.Stage 1 is characterized by the penetration of the skin by the female chigoe flea. Running along the body, the female uses its posterior legs to push its body upward by an angle of 45–90 degrees. Penetration then starts, beginning with the proboscis going through the epidermis.By stage 2 (day 1–2), penetration is complete and the flea has burrowed most of its body into the skin. Only the anus, the copulatory organs, and four rear air holes in fleas called stigmata remain on the outside of the epidermis.