The unique characteristics of Thai Leber hereditary optic neuropathy: analysis of 30 G11778A pedigrees

Leber hereditary optic neuropathy (LHON) is characterized by acute or subacute bilateral visual loss, and affects mostly young males. The most common mitochondrial DNA mutation responsible for LHON worldwide is G11778A. Despite different genetic backgrounds, which are believed to influence the disease expression, most features of LHON are quite common in different populations. However, there seem to be a few ethnic-specific differences. Analyses of our 30 G11778A LHON pedigrees in Thailand showed some characteristics different from those of Caucasians and Japanese. In particular, our pedigrees showed a lower male to female ratio of affected persons (2.6:1) and much higher prevalence of G11778A blood heteroplasmy (37% of the pedigrees contained at least one heteroplasmic G11778A individual). Heteroplasmicity seemed to influence disease manifestation in our patients but did not appear to alter the onset of the disease. The estimated overall penetrance of our G11778A LHON population was 37% for males and 13% for females. When each of our large pedigrees were considered separately, disease penetration varied from 9 to 45% between the pedigrees, and also varied between different branches of the same large pedigree. Survival analysis showed that the secondary LHON mutations G3316A and C3497T had a synergistic deleterious effect with the G11778A mutation, accelerating the onset of the disease in our patients.     

Potassium iodate toxic retinopathy: a report of five cases

BACKGROUND: Potassium iodate (KIO3) is an iodized salt used for iodine supplementation in areas endemic for goiter. KIO3 overdose in humans is rare. The authors report unusual cases of retinal toxicity from KIO3 overdose that caused acute vision loss. METHODS: The clinical manifestations, toxic dosage of iodate, and ocular changes in five patients who had taken a KIO3 overdose were analyzed. Electroretinography, visual evoked potential (VEP), and fundus fluorescein angiography (FA) were performed to study retinal function and changes. RESULTS: Two men and three women (age 22-65 years) ingested KIO3 solution at a concentration between 187 and 470 mg/kg body weight. Visual acuity ranged from light perception with projection to counting fingers and decreased from 2 to 12 hours after ingestion. Fundus FA showed bilateral extensive areas of retinal pigment epithelial (RPE) window defects, and electroretinography and VEP showed marked impairment of retinal function. Visual acuity improved from counting fingers to 20/80 in 3 months. CONCLUSION: Potassium iodate can produce retinal toxicity that damages RPE and photoreceptor cells. The recovery of retinal function depends on the amount of chemical absorption, the regeneration of RPE, and the recovery function of photoreceptor cells.     

Leber's hereditary optic neuropathy in Thailand.

PURPOSE: To study the clinical features of Leber's hereditary optic neuropathy (LHON) in Thai patients as compared with patients in the United States, Europe, and other Asian countries. METHODS: The blood mitochondrial DNA of patients from 19 Thai pedigree families was studied for LHON mutation by restriction enzyme analysis. RESULTS: Mitochondrial mutation at nucleotide position 11778 was detected in 37 affected patients and 21 unaffected maternal relatives. Ten of the 19 families were sporadic in transmission. The male preponderance in affected patients was 76%. The onset of visual loss ranged from 6 to 53 years of age (mean = 21.5 years). Of the 31 patients whose eyes were affected bilaterally, 48.4% developed visual loss simultaneously. Unilateral visual loss was found in 2 patients but 1 already had a blind eye resulting from trauma. Onset interval between eyes was up to 12 months (mean = 2.3 months). No associated heart disease or neurological disorder was detected in our pedigrees. Hyperemic disc, retinal telangiectasia, and tortuosity of vessels appeared on ophthalmoscopy in 29% of the patients. Final visual outcome was 0.1, or worse in 82.3%, with a mean follow-up period of 19.5 months. CONCLUSION: The clinical features of LHON in Thai patients are similar to those found in patients harboring the 11778 mutation in the United States, Europe, and Japan. However, although there is a male predominance in all populations studied, this is not so marked in the European and Thai populations.