Investigation of children for mitochondriopathy confirms need for strict patient selection, improved morphological criteria, and better laboratory methods

Electron microscopic findings in levator muscle biopsies of patients with isolated congenital or acquired ptosis

“…In a large study concerning ultrastructural findings in skeletal muscle biopsies from children with systemic mitochondriopathies, mitochondrial cytopathy was defined as quantitative (unusual size) and qualitative (unusual shape, abnormal patterns of cristae, abnormal matrix density) alterations [26]. Similarly, we are defining mitochondrial cytopathy by megamitochondria, alterations of mitochondrial matrix and abnormal cristae.…”

“…This is determined by the central role of mitochondria in the energy supply of the muscle fibre and the intracellular control of calcium, which can be adversely affected (directly or indirectly) in many conditions [38]. The fact that no specific biochemical and molecular defect could be associated with any particular structural alteration [4,39] determines the different specificity of the ultrastructural findings for the diagnosis of mitochondrial cytopathy [26,40,41]. In the present study, no muscle enzyme studies were performed due to lack of material.…”

“…In this regard and in view of limited health care resources, the development of an efficient diagnostic strategy [26,44] is a crucial challenge for the handling of patients with mitochondrial diseases possibly undergoing invasive tests and to prevent misdiagnoses [45][46][47][48][49], because the same nuclear or mitochondrial mutations can produce different clinical phenotypes [4].…”

Pathology of Adult and Paediatric Mitochondrial Myopathies

“…In 95 patients under 16 years of age, there was no difference in the frequency of SSMA between patients with and without definite mtD. Large SSMAs were observed to be more frequent in the group with definite mtD 152 . A large-scale retrospective study evaluating factors associated with SSMA in paediatric biopsies with suspected mtD found an inverse relationship between the percentage of myofibres with SSMA and RCE deficiency.…”

Importance of muscle light microscopic mitochondrial subsarcolemmal aggregates in the diagnosis of respiratory chain deficiency

“…A detailed description of this technique was described previously [23]. To avoid the artifactual overinterpretation of SSMA, only myofibers with crosssections, but not oblique sections, and areas without any folds were included in the calculation of the percentage of myofibers containing SSMA.…”