Sphingolipidoses Sandhoff disease is one of several forms of what was formerly known as amaurotic idiocy. This inherited disease is characterized by the accumulation of lipid-containing cells in the viscera and in the nervous system, mental retardation, and impaired vision or blindness. The chemical and enzymatic analysis of various patients with amaurotic idiocy by Konrad Sandhoff (1939- ), a German Biochemist, who led to the identification of several biochemically distinct diseases: The first biochemical description of GM1-gangliosidosis in 1963, Sandhoff disease in 1968, Tay-Sachs-Disease, the AB-variant of GM2-Gangliosidosis and the B1-variant of GM2-gangliosidosis. It came to the discovery of the molecular defect in Sandhoff disease, when Konrad Sandhoff studied the biochemistry of sphingolipids and gangliosides in the laboratory of Prof.
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In 1911 he was appointed director of a neurological sanatorium in Wiesbaden. In 1925 he moved to the spa town of Bad Pyrmont, where he worked as a medical hydrologist. He later opened a research institute of balneology in Breslau, but when the city became part of Poland, he returned to Bad Pyrmont. Vogt was amongst the first physicians to study "juvenile amaurotic familial idiocy" (Batten disease).
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By 1884, he had seen three cases in a single family. Years later, Bernard Sachs, an American neurologist, reported similar findings when he reported a case of "arrested cerebral development" to other New York Neurological Society members. Sachs, who recognized that the disease had a familial basis, proposed that the disease should be called amaurotic familial idiocy. However, its genetic basis was still poorly understood.
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In 1913–14, Max Bielschowsky delineated the late infantile form of NCL. However, all forms were still thought to belong in the group of "familial amaurotic idiocies", of which Tay–Sachs was the prototype. In 1931, Torsten Sjögren, a Swedish psychiatrist and geneticist, presented 115 cases with extensive clinical and genetic documentation and came to the conclusion that the disease now called the Spielmeyer-Sjogren (juvenile) type is genetically separate from Tay–Sachs.K. G. T. Sjögren.
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Horst Jatzkewitz (1912–2002), a German Biochemist (Max- Planck- Institute for Psychiatry, Munich). In October 1966, he obtained deep-frozen autopsy material from an infantile case with amaurotic idiocy. The glycolipid analysis soon demonstrated differences from all the cases studied before. Besides the neuronal storage of GM2, the storage of GA2 was much more pronounced, and different from all cases of Tay-Sachs disease studied so far, globoside accumulated in the visceral organs and, most importantly, hexosaminidase activity was almost completely absent.
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Leukocoria in a child with retinoblastoma Crossed eyes in a child with retinoblastoma The most common and obvious sign of retinoblastoma is an abnormal appearance of the retina as viewed through the pupil, the medical term for which is leukocoria, also known as amaurotic cat's eye reflex. Other signs and symptoms include deterioration of vision, a red and irritated eye with glaucoma, and faltering growth or delayed development. Some children with retinoblastoma can develop a squint, commonly referred to as "cross-eyed" or "wall-eyed" (strabismus). Retinoblastoma presents with advanced disease in developing countries and eye enlargement is a common finding.
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Although Gregor Mendel had published his article on the genetics of peas in 1865, Mendel's paper was largely forgotten for more than a generation – not rediscovered by other scientists until 1899. Thus, the Mendelian model for explaining Tay–Sachs was unavailable to scientists and doctors of the time. The first edition of the Jewish Encyclopedia, published in 12 volumes between 1901 and 1906, described what was then known about the disease: > It is a curious fact that amaurotic family idiocy, a rare and fatal disease > of children, occurs mostly among Jews. The largest number of cases has been > observed in the United States—over thirty in number.
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