Kasper Burkhard S, Thomas Christian, Albers Anne, Kasper Ekkehard M, Sandhoff Konrad
Friedrich-Alexander-Universität Erlangen-Nuremberg, University Hospital, Dept. Neurology; Erlangen, Germany.
Institute of Neuropathology, University Hospital Münster, Münster, Germany.
Free Neuropathol. 2023 Aug 8;4:12. doi: 10.17879/freeneuropathology-2023-4845. eCollection 2023 Jan.
On February 23 1936, a boy-child ("Kn") died in an asylum near Munich after years of severe congenital disease, which had profoundly impaired his development leading to inability to walk, talk and see as well as to severe epilepsy. While a diagnosis of "Little's disease" was made during life, his postmortem brain investigation at Munich neuropathology ("Deutsche Forschungsanstalt für Psychiatrie") revealed the diagnosis of "amaurotic idiocy" (AI). AI, as exemplified by Tay-Sachs-Disease (TSD), back then was not yet understood as a specific inborn error of metabolism encompassing several disease entities. Many neuropathological studies were performed on AI, but the underlying processes could only be revealed by new scientific techniques such as biochemical analysis of nervous tissue, deciphering AI as nervous system lipid storage diseases, e.g. GM2-gangliosidosis. In 1963, Sandhoff & Jatzkewitz published an article on a "biochemically special form of AI" reporting striking differences when comparing their biochemical observations of hallmark features of TSD to tissue composition in a single case: the boy Kn. This was the first description of "GM1-Gangliosidosis", later understood as resulting from genetically determined deficiency in beta-galactosidase. Here we present illustrative materials from this historic patient, including selected diagnostic slides from the case "Kn" in virtual microscopy, original records and other illustrative material available. Finally, we present results from genetic analysis performed on archived tissue proving beta-galactosidase-gene mutation, verifying the 1963 interpretation as correct. This synopsis shall give a first-hand impression of this milestone finding in neuropathology. On a biochemically special form of infantile amaurotic idiocy. Jatzkewitz H., Sandhoff K., Biochim. Biophys. Acta 1963; 70; 354-356. See supplement 1.
1936年2月23日，一名男童（“Kn”）在慕尼黑附近的一家精神病院去世，此前他患有多年严重的先天性疾病，这种疾病严重损害了他的发育，导致他无法行走、说话和视物，还伴有严重的癫痫。生前诊断为“里特尔氏病”，但在慕尼黑神经病理学研究所（“德国精神病学研究机构”）对其进行的尸检脑部检查显示，诊断结果为“黑蒙性白痴”（AI）。当时，以泰-萨克斯病（TSD）为例的AI尚未被理解为一种包含多种疾病实体的特定先天性代谢错误。人们对AI进行了许多神经病理学研究，但只有通过诸如神经组织生化分析等新科学技术才能揭示其潜在过程，将AI解读为神经系统脂质贮积病，例如GM2神经节苷脂沉积症。1963年，桑多夫和雅茨凯维茨发表了一篇关于“AI的一种生化特殊形式”的文章，报告了在将他们对TSD标志性特征的生化观察结果与一个病例（男孩Kn）的组织成分进行比较时发现的显著差异。这是对“GM1神经节苷脂沉积症”的首次描述，后来被理解为由β-半乳糖苷酶的基因决定缺陷导致。在此，我们展示了来自这位具有历史意义的患者的说明性材料，包括虚拟显微镜下病例“Kn”的选定诊断玻片、原始记录和其他可用的说明性材料。最后，我们展示了对存档组织进行基因分析的结果，证明了β-半乳糖苷酶基因突变，证实了1963年的解释是正确的。本综述将让人们对神经病理学这一里程碑式的发现有一个第一手的印象。关于婴儿黑蒙性白痴的一种生化特殊形式。雅茨凯维茨H.，桑多夫K.，《生物化学与生物物理学报》1963年；70；354 - 356。见补充材料1。
