Early-onset Behr syndrome due to compound heterozygous mutations in OPA1

Neuroradiological findings expand the phenotype of OPA1-related mitochondrial dysfunction

“…Various degrees of cortical or cerebellar atrophy, aspecific white matter hypersignal, brain calcifications, and multiple sclerosis-like white matter lesions, have been described in single case reports [10,11,14] and then found in 12 out of 40 ADOAplus patients [15], while no morphological brain abnormality was found in 13 pure ADOA patients [16] (19). More recently, atrophy of the cerebellar vermis, white matter hypersignal and lactate peak were identified in three patients harboring compound heterozygous OPA1 mutation and exhibiting a severe neurosensorial phenotype [17]. Although detection of central nervous system lactate by magnetic resonance spectroscopy (MRS) represents a useful tool to investigate patients with mitochondrial respiratory chain dysfunction [18,19], brain MRS results have only been rarely reported and were normal in OPA1 ADOA patients [12,20].…”

OPA1-related disorders: Diversity of clinical expression, modes of inheritance and pathophysiology

“…A few patients with DOA and neurosensory deafness (DOAD) were initially reported (Amati- Bonneau et al, 2003, and larger studies later showed that deafness was the most frequent extraocular feature, found in about 6% of all OPA1 patients (Leruez et al, 2013). As in the case of optic neuropathy, this sensorineural hearing loss was progressive, with mild to severe forms of the disorder appearing during the first two decades of life.…”

“…Fundamental research and clinical studies have led to the progressive understanding of mitochondrial dynamics and quality control. In particular, neurological suffering has been identified as the main deleterious consequence of defective mitochondrial dynamics (Bossy-Wetzel et al, 2003;Dupuis, 2014). OPA1-related disorders may serve as a paradigm of the processes involved in neurodegeneration since they are associated with a great diversity of neuronal dysfunctions resulting from the impairment of mitochondrial plasticity.…”

In vivo time-lapse imaging of mitochondria in healthy and diseased peripheral myelin sheath

“…Intriguingly GDAP1 has been involved both in axon-related disease CMT2K (Cassereau et al, 2011) and myelinrelated disease CMT4A (Kabzińska et al, 2014), suggesting that mitochondria of both glia and axons are involved. Moreover mutations in OPA1 (optic atrophy 1), a gene essential for mitochondria fusion, were recently shown to give rise to systemic neurodegeneration including a peripheral neuropathy with features of axonal degeneration and demyelination (Bonneau et al, 2014;Yu-Wai-Man et al, 2010). Together these data indicate that glial and axonal mitochondria are central to the maintenance of the intimate axon-myelin relationship and the modulation of their physiology may provide an opportunity to treat peripheral nerve diseases.…”