title: A case of excessive autophagocytosis with multiorgan involvement and low clinical penetrance.
abstract: An autopsy and microscopic analyses of a 74-year-old female with a clinical history of cardiac hypertrophy and hypertension disclosed a pronounced distension of lysosomal compartment with signs of excessive autophagocytosis, predominantly in cardiomyocytes, hepatocytes and smooth muscle cells of the small intestine. The histological storage pattern did not correspond to the usual changes seen in defined lysosomal storage disorders. The amount of age-related lipopigment was low in all tissues. Confocal microscopy of liver tissue samples documented a progressive loss of mitochondrial epitopes in the distended lysosomal compartment along the porto-central axis of hepatic lobules. The possibility to detect subunit c of mitochondrial ATP synthase (SCMAS) indicated extensive intra-lysosomal degradation of mitochondria, both in hepatocytes and smooth muscle cells. The SCMAS epitope can thus be considered a valuable immunohistochemical marker of autophagocytic mitochondrial degradation. The distended lysosomes also displayed tissue specific ubiquitination. Absence of immuno-detectable p62 protein excluded aggresome formation. An inherent dysfunction of the late endosomal/lysosomal LAMP2 protein (Danon disease), was excluded on the basis of LAMP2 gene sequence analysis and LAMP2 protein levels. Whether the observed process reflects a primary dysregulation of the constitution of the autophagosomal membrane or was induced by defects in other cellular components, remains unanswered. Whatever mechanism involved, the findings should be considered relevant in differential diagnostics, despite their low clinical penetrance, should be registered and thus rendered available for future definition.
authors.affiliation: Institute of Inherited Metabolic Disorders, 1st Medical Faculty, Charles University and General Teaching Hospital, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Sikora
authors.forename: L
authors.initials: L
authors.lastname: Dvoráková
authors.forename: H
authors.initials: H
authors.lastname: Vlásková
authors.forename: L
authors.initials: L
authors.lastname: Stolnaja
authors.forename: J
authors.initials: J
authors.lastname: Betlach
authors.forename: J
authors.initials: J
authors.lastname: Spacek
authors.forename: M
authors.initials: M
authors.lastname: Elleder
mesh_terms: D000368:Aged; D001343:Autophagy; D005260:Female; D006331:Heart Diseases / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D008171:Lung Diseases / Q000175:diagnosis* / Q000473:pathology