Mitochondrial Syndromes Revisited

Abstract

In the last ten years, the knowledge of the genetic basis of mitochondrial diseases has significantly advanced. However, the vast phenotypic variability linked to mitochondrial disorders and the peculiar characteristics of their genetics make mitochondrial disorders a complex group of disorders. Although specific genetic alterations have been associated with some syndromic presentations, the genotype-phenotype relationship in mitochondrial disorders is complex (a single mutation can cause several clinical syndromes, while different genetic alterations can cause similar phenotypes). This review will revisit the most common syndromic pictures of mitochondrial disorders, from a clinical rather than a molecular perspective. We believe that the new phenotype definitions implemented by recent large multicenter studies, and revised here, may contribute to a more homogeneous patient categorization, which will be useful in future studies on natural history and clinical trials.

Keywords: CPEO; Leigh syndrome; MELAS; MERRF; MNGIE; NARP; PEO; leber; mitochondrial myopathy; mtDNA.

Figure 1

Histological findings in mitochondrial myopathy. (A,B) Ragged red fiber (Hematoxylin–Eosin and Gomori’s staining, respectively, at the center of each panel), (C) cytochrome c oxidase (COX)-negative fibers (“white” fibers, COX staining), and (D) “Ragged blue” fibers (SDH (succinate dehydrogenase) staining).

Figure 2

Stroke-like lesion. Magnetic resonance (A) and histopathological (B) findings. Panel B shows a brain biopsy from a MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) patient, with “red neurons” and spongiosis with reactive astrocytosis in the cortex and the white matter (Hematoxylin–Eosin).