Morphological investigation of two sibling autopsy cases of mitochondrial trifunctional protein deficiency

Two sibling autopsy cases of type 2 mitochondrial trifunctional protein (MTP) deficiency are described. MTP is an enzyme complex involved in the mitochondrial beta-oxidation of fatty acids, which is the major pathway for energy production in heart and skeletal muscle. Both cases showed similar pathological findings. Numerous small foci of degeneration of muscle cells and cardiac myocytes were detected. Some of these cells had condensed or fragmented nuclei and most of them were positively stained using the deoxyuridine triphosphate nick-end labeling method. The lipid staining of both cases showed a small- to medium-sized fatty, vesicular morphology for liver cells, muscle cells, cardiac myocytes and proximal tubular cells of the kidney. Bone marrow was severely hypoplastic, and cortical thymocytes were markedly reduced in number. Neither case had hepatic fibrosis nor cirrhosis. The definitive diagnosis of type 2 MTP deficiency was made by verifying completely defective MTP-alpha and MTP-beta subunits in cultured skin fibroblasts of one of 2 patients. Our patients' signs indicate that there is a wider pathological spectrum of type 2 MTP deficiency, while very few autopsy cases of type 2 MTP deficiency have been confirmed. Pathologists should consider the possibility of type 2 MTP deficiency or other beta-oxidation defects in cases of sudden infant death, fatty infiltration of viscera or cardiomyopathy.