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

Abstract

PURPOSE. Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease in which optic neuropathy is considered a key feature. Several other manifestations of LHON have been reported; however, only little is known of their incidence and the life expectancy in LHON patients.METHODS. This study, based on Danish nationwide health registries, included 141 patients diagnosed with LHON and 297 unaffected family members in the maternal line. The incidence of comorbidities and mortality for patients with LHON and unaffected family members was compared with that in the general population.RESULTS. Having LHON was associated with an almost 2-fold risk of mortality with a rate ratio (RR) of 1.95 (95% confidence interval [CI]: 1.47-2.59; P < 0.001). The incidence of several diseases was increased for LHON patients, but not for family members. The incidence of stroke was 5.73 per 1000 patient-years for LHON patients compared to 2.33 for the general population, and the RR was 2.38 (95% CI: 1.58-3.58; P < 0.001). The incidence of demyelinating disorders was 2.24 compared to 0.21 for the general population; RR was 12.89 (95% CI: 6.70-24.77; P < 0.001). A 4-fold risk of dementia was seen for LHON patients (RR: 4.26, 95% CI: 1.91-9.48; P < 0.001), incidence 1.45 for LHON and 0.37 for the general population. Moreover, LHON patients had an increased risk of epilepsy, atherosclerosis, nerve symptoms, neuropathy, and alcohol-related disorders.CONCLUSIONS. The manifestation of LHON was associated with increased mortality and increased incidence of several disorders including stroke, demyelinating disorder, dementia, and epilepsy.

Sulthiame impairs mitochondrial function in vitro and may trigger onset of visual loss in Leber hereditary optic neuropathy

“…A multiple sclerosis-like condition (or "Harding´s disease") was observed in some subjects with LHON, mostly women [15,23]. A recent nationwide study from Denmark revealed an increased incidence for stroke, demyelinating disorders, dementia, and epilepsy in individuals with LHON, but not in their family members [24]. Focal epilepsy in childhood, as observed in the two subjects reported here, is unusual to occur in patients with LHON.…”

Leber’s Hereditary Optic Neuropathy and Hypertrophic Cardiomyopathy

“…Patients with LHON was shown to have a twice as high all cause mortality rate as well as significantly higher incidences of heart related diseases and stroke compared to the background population (12,4/1000 versus 5,2/1000 patient years). 4 The results from these previous studies suggest that LHON is associated with the development of cardiac manifestation at least in carriers of the recognized pathogenic ND1 variant (m.3460G>A), although data from cardiac investigations was only available in one study. 1,3 These findings suggests that patients with LHON and their relatives carrying ND1 variants should be offered routine cardiac investigation including ECG and echocardiography.…”

Can the effects of the mitochondrial DNA mutations found in Leber’s hereditary optic neuropathy be protective against the development of cluster headache in smokers?

“…A recent Danish population-based study of LHON did not elicit any significant comorbid migraine history above the general population and CH was not noted. 11…”