Leber’s hereditary optic neuropathy is multiorgan not mono-organ

Abstract

Leber’s hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder with bilateral loss of central vision primarily due to mitochondrial DNA (mtDNA) mutations in subunits of complex I in the respiratory chain (primary LHON mutations), while other mtDNA mutations can also be causative. Since the first description, it is known that LHON is not restricted to the eyes but is a multisystem disorder additionally involving the central nervous system, ears, endocrinological organs, heart, bone marrow, arteries, kidneys, or the peripheral nervous system. Multisystem involvement may start before or after the onset of visual impairment. Involvement of organs other than the eyes may be subclinical depending on age, ethnicity, and possibly the heteroplasmy rate of the responsible primary LHON mutation. Primary LHON mutations may rarely manifest without ocular compromise but with arterial hypertension, various neurodegenerative diseases, or Leigh syndrome. Patients with LHON need to be closely followed up to detect at which point organs other than the eyes become affected. Multiorgan disease in LHON often responds more favorably to symptomatic treatment than the ocular compromise.

Renal artery aneurysm associated with Leber hereditary optic neuropathy

“… 1 LHON is caused by various mutations of mitochondrial DNA, leading to the dysfunction of complex I of the respiratory chain. 2 , 3 It is thought that oxidative stress causes microangiopathic damage to retinal arteries. 4 Although vision loss is the defining characteristic of LHON, damage to other organ systems is seen.…”

“…LHON is inherited maternally with variable penetrance, affecting males more than females. 3 , 4 , 5 It has been suggested that LHON is a multiorgan disease and may present with various vascular manifestations. Macroangiopathic consequences are seen, including arterial hypertension and aortic disease.…”

Increased Mortality and Comorbidity Associated With Leber's Hereditary Optic Neuropathy: A Nationwide Cohort Study

“…[9][10][11][12] Unfortunately, these studies tend to include only small cohorts and investigate a limited number of additional manifestations. Likewise, few studies on mortality have been published.…”

Gene therapy and genome surgery in the retina

“…Preliminary results showed the therapy's safety, with minimal adverse effects and quantitative improvement in vision in two of five patients, though it is unclear whether this was due to the success of the vector or the nature of LHON, which has low rates of spontaneous recovery. Larger sample sizes will be required to determine the significance of improvements in the trial (150,151). A previous clinical trial for an intravitreally delivered AAV2.ND4 vector resulted in no adverse effects for the trial's nine patients, with a significant increase in visual acuity in six patients, without a change in retinal nerve fiber thickness (152,153).…”