Postmortal and Bioptic Findings in Hereditary Mitochondrial Beta OxidationDisorders. Role of Pathologist in the Diagnostic Process

Overview

Basic problems of the group of hereditary mitochondrial beta oxidation (BOX) disorders arepresented with evaluation of the role of pathologists in the diagnostic process. The disordersmanifest thelsemvels clinically as usual by recurrent Reye-like episodes (acute hepatopathy andencephalopathy) typically in low age levels. Integral part of the clinical picture is often a myopat-hic symptomatology which at some cases may display even persisting character. The findings atthe tissue level are dominated mostly by steatosis of the organ set with a high beta oxidation level(liver, heart, skeletal muscle, kidney) and toxic effects of the intermediate metabolic products ofthe derranged beta oxidation process. So far eighteen enzyme defects have been described affec-ting either transport of fatty acids acros the mitochondrial membranes or their oxidative degra-dation at various levels, pointing to an absolute dependence of the final diagnosis on biochemicalanalysis. Pathologist’s conclusion in cases dying without diagnosis is limited to suspicion ofa BOX disorder only. However, pathologists can contribute significantly to unraveling and specifi-cation of the underlying BOX defect by collecting adequate samples of body fluids and of unfixedorgans. Nevertheless, the validity of these samples, even if widely recognized, is limited. The bestapproach is to provide samples enabling to perform biochemical evaluation of the whole BOXprocess in integral mitochondrias. This requirement is fulfilled solely by establishing fibroblasttissue culture post mortem.

Key words:
beta oxidation of fatty acids - steatosis - enzymopathy - postmortal diagnosis