“Mitochondrial neuropathies”: A survey from the large cohort of the Italian Network
Introduction
The central task of mitochondria is to generate energy in the form of adenosine triphosphate, through the electron transport chain and oxidative phosphorylation (OXPHOS) [1]. This pathway is under control of both nuclear and mitochondrial (mtDNA) genomes. Mitochondrial diseases are a group of disorders caused by OXPHOS impairment. They are one of the commonest inherited neuromuscular diseases, with an estimated prevalence of 1–2 in 10,000. The genetic classification distinguishes the disorders due to defects in mtDNA from those due to defects in nuclear DNA.
Both mtDNA and nuclear mutations affecting OXPHOS usually result in multisystem clinical phenotypes, including peripheral neuropathy [2]. Peripheral neuropathy is a defining feature in some mitochondrial disorders such as SANDO (sensory ataxic neuropathy, dysarthria and ophthalmoplegia), NARP (neuropathy, ataxia and retinitis pigmentosa), or MNGIE (mitochondrial neuro-gastro-intestinal encephalomyopathy) [3], and occasionally is the prevalent disease manifestation [4], [5]. However, the exact prevalence of peripheral neuropathy in mitochondrial disorders is still unknown [6].
The aim of this retrospective study is to evaluate the minimum prevalence of peripheral neuropathy in patients with mitochondrial disorders, taking advantage of the large database built by the “Nation-wide Italian Collaborative Network of Mitochondrial Diseases”. Specific genotype–phenotype correlations are highlighted.
Section snippets
Methods
We reviewed the clinical data of all of the 1200 histologically, biochemically and/or molecularly defined patients present in our “Nation-wide Italian Collaborative Network of Mitochondrial Diseases” database (updated on December 31, 2014) and followed up by the involved centers, focusing on peripheral neuropathy as a clinical feature of a mitochondrial disorder.
The database establishment (and its use for scientific purposes) was permitted by the local Ethical Committees of the single centers,
Results
The clinical picture was fully available for 1156 patients (mean age at onset 24.3 ± 20.1 years; age at last evaluation 39.8 ± 22.3 years; females 52.7%; childhood onset [before age 16 years] 43.1%). Peripheral neuropathy was part of the clinical picture in 143/1156 patients (12.4%), being the tenth most frequent clinical manifestation (Table 1). In 33 patients, neuropathy was present at the onset of the disease.
In order to understand if the presence (or absence) of peripheral neuropathy was
Discussion
Despite the great progress in our genetic and clinical understanding of mitochondrial disorders, the prevalence of peripheral neuropathy is still unknown. Most of the published studies have examined single cases or families, or have been conducted by recruiting a limited number of patients [7]. Girlanda et al. analyzed 27 patients with unselected mitochondrial disease, and observed axonal neuropathy in six cases (18%) [8]. Mancuso et al. [9] showed electrophysiologically that peripheral
Acknowledgements
This study was supported by Telethon Grant GUP09004. The authors are grateful to the patients' association MITOCON for the web-platform assistance. MITOCON has also supported Dr Orsucci's work.
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Both authors contributed equally to this work.