Edgar von Gierke (1877-1945) - Eponym of "von Gierke disease" and double victim of National Socialism.

As recent studies on the Third Reich have shown, a two-digit number of Jewish pathologists fell victim to National Socialist repression. One of them was Edgar von Gierke. His name is nowadays best known in medicine for discovering the "von Gierke disease" - also classified as "Glycogen storage disease type I" - which he first described in 1929. This article deals with the role of von Gierke as a persecuted and disenfranchised Jew. Accordingly, the focus is on von Gierke's repressive experiences in the Third Reich, which were quite different from other cases. It is based on (1) previously partly unnoticed archival sources and (2) a re-analysis of the relevant research literature. The paper shows that Edgar von Gierke was a double victim of Nazi Germany, even though he was able to maintain his professional position for a comparatively long time: In contrast to other Jews who were dismissed in 1933 on the basis of the "Aryan paragraph", von Gierke benefited from a legal exception as a decorated front fighter in the First World War. It was not until 1937 that he was released from public service. Even more striking is the fact that von Gierke was ordered back to his old position twice between 1939 and 1944 due to a lack of personnel. The evaluation of archival files leads to the conclusion that von Gierke was recalled to work under pressure from leading National Socialists and that this ordered reappointment had a devastating effect on his health status. At that time the pathologist was already suffering from a progressive heart disease, to which he succumbed in autumn 1945 - fatally only a few month after the fall of the Third Reich.

Historical highlights and unsolved problems in glycogen storage disease type 1.

UNLABELLED: Thirty-three years after Von Gierke described the first patient with glycogen storage disease type 1 (GSD1) in 1929, the Coris detected glucose-6-phosphatase (G6Pase) deficiency. The first mutation of this enzyme was identified 41 years later and subsequently the gene was mapped to chromosome 17q21, its enzyme topology defined, a nine transmembrane helical model suggested, an enzyme deficient knockout mouse created and by infusing an adenoviral vector associated murine G6Pase gene, correction of the clinical and laboratory abnormalities was observed. A similar successful gene transfer has been performed in enzyme deficient canine puppies. To explain the function of the G6Pase complex, a multicomponent translocase catalytic model has been proposed in which different transporters shuttle glucose-6-phosphate (G6P), inorganic phosphate (Pi) and glucose across the microsomal membrane. It was suggested that GSD1b patients suffered from a G6P transporter (G6PT) defect and the first mutation in the G6PT gene subsequently recognised. The gene mapped to chromosome 11q23 and its structural organisation was defined which showed a close functional linkage between G6PT and hydrolysis. Nordlie identified the first patient with Pi transport deficiency (GSD1c). However putative GSD1c and 1d patients based on kinetic studies were found to harbour mutations in the G6PT gene so that GSD1 patients are presently divided into 1a and non-1a. G6PT deficient patients suffer from numerical and functional leucocyte defects. A mRNA leucocyte G6PT deficiency has been suggested to account for the glucose phosphorylation and subsequent calcium sequestration defects observed in theses cells. Inflammatory bowel disease which occurs frequently in GSD non-1a patients has been related to their leucocyte abnormalities. Dietary management of GSD1 patients, designed to maintain a normal blood glucose level can be achieved during the night by nocturnal gastric infusions of glucose-containing solution or by the administration of uncooked cornstarch around the clock or by a combination of both. Both therapeutic modalities, if conducted in a meticulous manner, have a major impact on the quality of life, prevention of complications and subsequent prognosis. Open questions relate to the source of endogenous glucose production in GSD1 patients which increases as a function of age from 50% to 100% of normal, concomitant with an improvement in the patients fasting tolerance. Several complications, the nature of which is incompletely understood, tend to occur after the first decade: Liver adenomata with a small risk of transforming into hepatoma, progressive renal disease, which may be related to the hyperlipidaemia observed in this disease, often leading to end stage renal failure, osteopenia apparently based on high bone turnover, growth retardation and delayed puberty. CONCLUSION: this review highlights the present knowledge of glycogen storage disease type 1 and subtypes, discussing unsolved questions, which reflect the limitation of our knowledge in the understanding of this intriguing group of diseases.