Table 1.
Summaries of the case histories of the four patients.
Fig 1.
Liver and brain pathology for Patient 1.
Post-mortem liver samples from patient 1 (a and b) showed perivenular foci of enlarged hepatocytes with fine vacuolation (arrows). On lipid staining with oil red O (b) of frozen sections there was diffuse lipid deposition. Sample of the cerebral cortex from the occipital lobe showed full thickness neuronal loss with vacuolation and astrocytosis (c and d). Samples of the hippocampi (e and f) showed segmental neuronal loss, most marked from CA1 (arrow) and gliosis in a similar pattern (f-GFAP). Scale bars, a and b = 100 μm; c and d = 200 μm; e and f = 2 mm.
Fig 2.
Brain and muscle pathology for patient 2.
A brain biopsy from patient 2 showed a little neuropil vacuolation (a) and cortical gliosis (b) but no specific diagnostic features. A muscle biopsy showed scattered cytochrome oxidase (COX)-negative fibres (f—arrows) but no other myopathic features (c) and no ragged red (d) or blue (e) fibres. Scale bars = 100 μm.
Fig 3.
Muscle pathology for patient 3.
Haematoxylin-Eosin stained section (A) showed mild variation in fibre size and several fibres with peripheral accumulation of mitochondria (arrowhead). Gomori trichrome preparation (B) accentuated ragged red fibres (arrowhead) and that for Succinic dehydrogenase (C) showed many ragged blue fibres (arrowheads). COX histochemical preparation (D) revealed frequent COX-deficient fibres (arrowheads) in keeping with mitochondrial myopathy. Scale bar = 50 μm.
Fig 4.
Muscle pathology for patient 4.
Succinic dehydrogenase revealed frequent ragged blue fibres (A—red arrowheads) and there were numerous COX-deficient fibres (B—red arrowheads) in keeping with mitochondrial myopathy. Scale bar = 50 μm.
Fig 5.
Long range PCR and Southern Blot analysis.
A. Long PCR of muscle mt DNA from the four patients. 1, 1kb ladder; 2, Muscle negative control; 3, Patient 2; 4, Patient 3; 5, water control; 6, Patient 4; 7, patient 1. B. Depletion of mtDNA obtained from liver of patient 1. 1, control; 2, control; 3, patient 1.
Table 2.
Muscle mtDNA resequencing data of the four patients.
Table 3.
The mitochondrial phenotypes and clinical features reported with homozygous A467T mutations.