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Light and electron microscopy characteristics of the muscle of patients with SURF1 gene mutations associated with Leigh disease.

Pronicki M, Matyja E, Piekutowska-Abramczuk D, Szymanska-Debinska T, Karkucinska-Wieckowska A, Karczmarewicz E, Grajkowska W, Kmiec T, Popowska E, Sykut-Cegielska J - J. Clin. Pathol. (2007)

Bottom Line: Diffuse decreased activity or total deficit of COX was revealed histochemically in all examined muscles.Lipid accumulation and fibre size variability were found in 14 and 9 specimens, respectively.In five cases no ultrastructural changes were found.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, The Children's Memorial Health Institute, Warsaw, Poland. mpronicki@poczta.onet.pl

ABSTRACT

Aims: Leigh syndrome (LS) is characterised by almost identical brain changes despite considerable causal heterogeneity. SURF1 gene mutations are among the most frequent causes of LS. Although deficiency of cytochrome c oxidase (COX) is a typical feature of the muscle in SURF1-deficient LS, other abnormalities have been rarely described. The aim of the present work is to assess the skeletal muscle morphology coexisting with SURF1 mutations from our own research and in the literature.

Methods: Muscle samples from 21 patients who fulfilled the criteria of LS and SURF1 mutations (14 homozygotes and 7 heterozygotes of c.841delCT) were examined by light and electron microscopy.

Results: Diffuse decreased activity or total deficit of COX was revealed histochemically in all examined muscles. No ragged red fibres (RRFs) were seen. Lipid accumulation and fibre size variability were found in 14 and 9 specimens, respectively. Ultrastructural assessment showed several mitochondrial abnormalities, lipid deposits, myofibrillar disorganisation and other minor changes. In five cases no ultrastructural changes were found. Apart from slight correlation between lipid accumulation shown by histochemical and ultrastructural techniques, no other correlations were revealed between parameters investigated, especially between severity of morphological changes and the patient's age at the biopsy.

Conclusion: Histological and histochemical features of muscle of genetically homogenous SURF1-deficient LS were reproducible in detection of COX deficit. Minor muscle changes were not commonly present. Also, ultrastructural abnormalities were not a consistent feature. It should be emphasised that SURF1-deficient muscle assessed in the light and electron microscopy panel may be interpreted as normal if COX staining is not employed.

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Ultastructural findings in the muscle of patients with Leigh syndrome associated with c. 841delCT SURF1 gene mutation. In a majority of patients (12 of 19 examined cases), several muscle fibres demonstrated distinct subsarcolemmal accumulation of altered mitochondria (B, C). Frequently, the mitochondria were markedly enlarged or elongated (C, D) and exhibited dark matrix with densely packed, concentrically arranged lamellal cristae (D, E). Occasionally, the mitochondrial matrix displaced spaces with amorphous granular material and small, electron-dense, osmophilic granules (D). Extensive accumulation of lipid deposits occurred in association with normal and altered mitochondria (F, G). Some muscle fibres revealed alterations of myofibrils including their focal or widespread disorganisation and/or disruption (A, H, I). Moreover, the tubulofilamentous structures typical of cytoplasmic body formation and subsarcolemmal aggregation of concentric laminated bodies were also found in individual cases (H). Original magnification: A, ×12 000; B, C, F, ×7500; D, G, ×15 000; E, ×10 000; H, ×20 000; I, ×3000.
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CPT-61-04-0460-f02: Ultastructural findings in the muscle of patients with Leigh syndrome associated with c. 841delCT SURF1 gene mutation. In a majority of patients (12 of 19 examined cases), several muscle fibres demonstrated distinct subsarcolemmal accumulation of altered mitochondria (B, C). Frequently, the mitochondria were markedly enlarged or elongated (C, D) and exhibited dark matrix with densely packed, concentrically arranged lamellal cristae (D, E). Occasionally, the mitochondrial matrix displaced spaces with amorphous granular material and small, electron-dense, osmophilic granules (D). Extensive accumulation of lipid deposits occurred in association with normal and altered mitochondria (F, G). Some muscle fibres revealed alterations of myofibrils including their focal or widespread disorganisation and/or disruption (A, H, I). Moreover, the tubulofilamentous structures typical of cytoplasmic body formation and subsarcolemmal aggregation of concentric laminated bodies were also found in individual cases (H). Original magnification: A, ×12 000; B, C, F, ×7500; D, G, ×15 000; E, ×10 000; H, ×20 000; I, ×3000.

Mentions: Ultrastructural examination of skeletal muscles biopsies revealed a spectrum of morphological abnormalities consisting mainly of more or less detectable mitochondrial alterations (fig 2). In a majority of patients (12 of 19 examined cases), several muscle fibres demonstrated distinct subsarcolemmal accumulation of altered mitochondria (fig 2B,C). Frequently, the mitochondria were markedly enlarged or elongated (fig 2C,D) and exhibited dark matrix with densely packed, concentrically arranged lamellar cristae (fig 2D,E). Occasionally, the mitochondrial matrix displaced spaces with amorphous granular material and small, electron-dense, osmophilic granules (fig 2D). Extensive accumulation of lipid deposits occurred in association with normal and altered mitochondria (fig 2F,G). Some muscle fibres revealed alterations of myofibrils including their focal or widespread disorganisation and/or disruption (fig 2A–H,I). Moreover, the tubulofilamentous structures typical of cytoplasmic body formation and subsarcolemmal aggregation of concentric laminated bodies were also found in individual cases (fig 2H).


Light and electron microscopy characteristics of the muscle of patients with SURF1 gene mutations associated with Leigh disease.

Pronicki M, Matyja E, Piekutowska-Abramczuk D, Szymanska-Debinska T, Karkucinska-Wieckowska A, Karczmarewicz E, Grajkowska W, Kmiec T, Popowska E, Sykut-Cegielska J - J. Clin. Pathol. (2007)

Ultastructural findings in the muscle of patients with Leigh syndrome associated with c. 841delCT SURF1 gene mutation. In a majority of patients (12 of 19 examined cases), several muscle fibres demonstrated distinct subsarcolemmal accumulation of altered mitochondria (B, C). Frequently, the mitochondria were markedly enlarged or elongated (C, D) and exhibited dark matrix with densely packed, concentrically arranged lamellal cristae (D, E). Occasionally, the mitochondrial matrix displaced spaces with amorphous granular material and small, electron-dense, osmophilic granules (D). Extensive accumulation of lipid deposits occurred in association with normal and altered mitochondria (F, G). Some muscle fibres revealed alterations of myofibrils including their focal or widespread disorganisation and/or disruption (A, H, I). Moreover, the tubulofilamentous structures typical of cytoplasmic body formation and subsarcolemmal aggregation of concentric laminated bodies were also found in individual cases (H). Original magnification: A, ×12 000; B, C, F, ×7500; D, G, ×15 000; E, ×10 000; H, ×20 000; I, ×3000.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2571978&req=5

CPT-61-04-0460-f02: Ultastructural findings in the muscle of patients with Leigh syndrome associated with c. 841delCT SURF1 gene mutation. In a majority of patients (12 of 19 examined cases), several muscle fibres demonstrated distinct subsarcolemmal accumulation of altered mitochondria (B, C). Frequently, the mitochondria were markedly enlarged or elongated (C, D) and exhibited dark matrix with densely packed, concentrically arranged lamellal cristae (D, E). Occasionally, the mitochondrial matrix displaced spaces with amorphous granular material and small, electron-dense, osmophilic granules (D). Extensive accumulation of lipid deposits occurred in association with normal and altered mitochondria (F, G). Some muscle fibres revealed alterations of myofibrils including their focal or widespread disorganisation and/or disruption (A, H, I). Moreover, the tubulofilamentous structures typical of cytoplasmic body formation and subsarcolemmal aggregation of concentric laminated bodies were also found in individual cases (H). Original magnification: A, ×12 000; B, C, F, ×7500; D, G, ×15 000; E, ×10 000; H, ×20 000; I, ×3000.
Mentions: Ultrastructural examination of skeletal muscles biopsies revealed a spectrum of morphological abnormalities consisting mainly of more or less detectable mitochondrial alterations (fig 2). In a majority of patients (12 of 19 examined cases), several muscle fibres demonstrated distinct subsarcolemmal accumulation of altered mitochondria (fig 2B,C). Frequently, the mitochondria were markedly enlarged or elongated (fig 2C,D) and exhibited dark matrix with densely packed, concentrically arranged lamellar cristae (fig 2D,E). Occasionally, the mitochondrial matrix displaced spaces with amorphous granular material and small, electron-dense, osmophilic granules (fig 2D). Extensive accumulation of lipid deposits occurred in association with normal and altered mitochondria (fig 2F,G). Some muscle fibres revealed alterations of myofibrils including their focal or widespread disorganisation and/or disruption (fig 2A–H,I). Moreover, the tubulofilamentous structures typical of cytoplasmic body formation and subsarcolemmal aggregation of concentric laminated bodies were also found in individual cases (fig 2H).

Bottom Line: Diffuse decreased activity or total deficit of COX was revealed histochemically in all examined muscles.Lipid accumulation and fibre size variability were found in 14 and 9 specimens, respectively.In five cases no ultrastructural changes were found.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, The Children's Memorial Health Institute, Warsaw, Poland. mpronicki@poczta.onet.pl

ABSTRACT

Aims: Leigh syndrome (LS) is characterised by almost identical brain changes despite considerable causal heterogeneity. SURF1 gene mutations are among the most frequent causes of LS. Although deficiency of cytochrome c oxidase (COX) is a typical feature of the muscle in SURF1-deficient LS, other abnormalities have been rarely described. The aim of the present work is to assess the skeletal muscle morphology coexisting with SURF1 mutations from our own research and in the literature.

Methods: Muscle samples from 21 patients who fulfilled the criteria of LS and SURF1 mutations (14 homozygotes and 7 heterozygotes of c.841delCT) were examined by light and electron microscopy.

Results: Diffuse decreased activity or total deficit of COX was revealed histochemically in all examined muscles. No ragged red fibres (RRFs) were seen. Lipid accumulation and fibre size variability were found in 14 and 9 specimens, respectively. Ultrastructural assessment showed several mitochondrial abnormalities, lipid deposits, myofibrillar disorganisation and other minor changes. In five cases no ultrastructural changes were found. Apart from slight correlation between lipid accumulation shown by histochemical and ultrastructural techniques, no other correlations were revealed between parameters investigated, especially between severity of morphological changes and the patient's age at the biopsy.

Conclusion: Histological and histochemical features of muscle of genetically homogenous SURF1-deficient LS were reproducible in detection of COX deficit. Minor muscle changes were not commonly present. Also, ultrastructural abnormalities were not a consistent feature. It should be emphasised that SURF1-deficient muscle assessed in the light and electron microscopy panel may be interpreted as normal if COX staining is not employed.

Show MeSH
Related in: MedlinePlus