Special issue Heidelberg Heart II: Abstracts of oral and poster presentations

Abstract

In view of the recently increased recognition of the frequency of ARVC/D patients carrying mutations in constitutive molecular components of the cytoskeleton and the specific junctions (composite junctions, areae compositae) of the cardiomyocyte-connecting intercalated disk (see, e.g., van Tintelen, A14, as well as Rickelt and Pieperhoff, special article, in this issue), it is now necessary to consider the very high ratio of young persons who take anabolic-androgenic steroids (AAS) for the promotion of muscle growth and for athletic performance enhancements, including athletes as well as “bodybuilders” and persons in show business. Although cross-striated skeletal muscle is the desired target tissue of this drug abuse, it was not surprising to learn that cross-striated myocardiac muscle can also increase in size and protein mass (for early animal experiments and reviews, see 'Special Reference List'). This possible coincidence of a genetic predisposition and widespread drug abuse is therefore a special subject of concern, notably in connection with discussions of cases of “sudden death” of active or former AAS abusers. As this drug abuse usually occurs in deeply conspirative secrecy and the persons involved, including family members, coaches, dealers, and sports functionaries, will remain silent, it would need a rare and special combination of circumstances to collect and publish the information needed to present a specific case. Therefore, we thankMr. Gerd L. Jacobs, born April 4, 1960, in Berlin, for permission to present his case at this meeting. A slightly condensed summary of his life history is presented in the protocol of his interrogation by the police in the city of Berlin for the County Court Prosecutors on February 2 1998 (an English summary of the protocol can be read on the author's website at http://www.dkfz.de/en/ helmholtz-zellbiologie/starting-page-Helmholtz.html). Mr. Jacobs was an active athlete (track and field) in shot-put and discus throw in the Berlin sports club TSC from 1972 to 1984, and finished his sports career as a sports teacher (in the last years of his career he was among the top-ten of the German Democratic Republic, GDR). His closest club teammates in shot-put included Ulf Timmermann, Olympic gold medal winner, former world record holder and still European record holder.Mr. Jacobs received the oral drug Oral-Turinabol (OT), a 17-α-alkylated steroid, the most frequently used AAS in GDR sports (Franke and Berendonk 1997). He received the pills directly from the coach and was never informed about possible AAS-induced damages or harmful side-effects. The daily dose varied between two and eight pills, i.e., 10-40 mg. In later years, the dosage was reduced to half. The drug was given in two annual “cycles”, each for 4 months. After 1998 the cardiac health of Mr. Jacobs deteriorated dramatically and rapidly, so that on October 1 2004 his heart had to be replaced by a donor heart. The major statement in the histological diagnosis was “high-grade cardiac muscle hypertrophy with secondary myocardiac damages and myocardial disarrangements”. Independently, and not aware of the AAS drug history, Posch et al. (2008) had found that the explanted heart as well as other tissues of Mr. Jacobs contained two missense mutations in the gene encoding desmoglein-2 (V55Mand V919G), i.e., one of the two cadherin-type transmembrane glycoproteins of the desmosomal type (Schäfer et al. 1994, 1996), the importance of which for the development and functions in non-epithelial tissues was first demonstrated by Eshkind et al. (2002). Mr. Jacobs has been reported as homozygous for DSG-V55M, and his father has subsequently been found to be heterozygous for this mutation but also suffering from “dilated cardiomyopathy”. Ultrastructural alterations have been reported for the intercalated disk junctions of the explanted heart, including electron microscopy (Posch et al. 2008). As similar heart problems, including hypertrophic and dilated cardiomyopathies, have also been found in AAS-treated power athletes and bodybuilders (see 'Special Reference List'), the combinations of both situations, i.e. gene mutations in one of the constitutive molecules of the composite junctions (areae compositae) of the myocardial intercalated disks (for Dsg2 see, for example, Borrmann et al. 2006; Franke et al. 2006; for further recent reports on Dsg2 mutations in cardiac diseases, see the reference thesaurus in the article by Pieperhoff and Rickelt in this issue) and AAS-treatment (one of the most spectacular cases in Berlin was that of the former shot-put European vice champion Ralf Reichenbach, 48 years old), have to be considered and discussed as a special possible cause for the specific pathogenic developments.