The Eye on Mitochondrial Disorders.

Ophthalmologic manifestations of mitochondrial disorders are frequently neglected or overlooked because they are often not regarded as part of the phenotype. This review aims at summarizing and discussing the etiology, pathogenesis, diagnosis, and treatment of ophthalmologic manifestations of mitochondrial disorders. Review of publications about ophthalmologic involvement in mitochondrial disorders by search of Medline applying appropriate search terms. The eye is frequently affected by syndromic as well as nonsyndromic mitochondrial disorders. Primary and secondary ophthalmologic manifestations can be differentiated. The most frequent ophthalmologic manifestations of mitochondrial disorders include ptosis, progressive external ophthalmoplegia, optic atrophy, retinopathy, and cataract. More rarely occurring are nystagmus and abnormalities of the cornea, ciliary body, intraocular pressure, the choroidea, or the brain secondarily affecting the eyes. It is important to recognize and diagnose ophthalmologic manifestations of mitochondrial disorders as early as possible because most are accessible to symptomatic treatment with partial or complete short-term or long-term beneficial effect. Ophthalmologic manifestations of mitochondrial disorders need to be appropriately diagnosed to initiate the most effective management and guarantee optimal outcome

Detection of the mutation may guide treatment of heart and muscle in Duchenne muscular dystrophy

Josef Finsterer,1 Sinda Zarrouk-Mahjoub21Krankenanstalt Rudolfstiftung, Vienna, Austria; 2Genomics Platform, Pasteur Institute of Tunis, Tunis, Tunisia We read with great interest the article, by Kono et al, about a 32-year-old male with Duchenne muscular dystrophy (DMD), who was admitted for dilated cardiomyopathy manifesting as heart failure, left bundle branch block, Mobitz-II block, bradycardia, and arterial hypotension. He profited from implantation of a cardiac resynchronization therapy-D system with a defibrillator and beta-blocker treatment. View original article by Kono et al. &nbsp

Phenotypic heterogeneity of a compound heterozygous SUCLA2 mutation

cited By 1International audienceWith interest we read the article by Huang et al. about two siblings carrying both the same compound heterozygous SUCLA2 mutation, which manifested phenotypically with a progressive multisystem syndrome, resulting in severe disability (patient-1) or death (patient-2). We have the following comments and concerns.Patient-1 was treated with dichloroacetate (DCA) over at least 4y. DCA is well-known for its neurotoxicity in MELAS patients, resulting in severe polyneuropathy. To which degree was the continuous deterioration of the phenotype attributable to the mitochondrion-toxic effect of DCA? Was polyneuropathy by age 1y attributed to the SUCLA2 mutation or interpreted as side effect of DCA? Was polyneuropathy a complication of diabetes

Mitochondrial myopathy, dysmorphism, exercise-induced vomiting and tachycardia the mutation m.4831G > A

cited By 0International audienceWith interest we read the article by Zanolini et al. about a 21 year-old male with isolated myopathy due to the ND2 mutation m.4831G > A. We have the following comments and concerns.We do not agree that the patient had myopathy as the sole manifestation of the mitochondrial disorder (MID). The patient started with vomiting during exercise since age 17 years, a frequent manifestation of MIDs particularly in patients with MELAS and possibly associated with lactic acidosis. Additionally, he had bone abnormalities, manifesting as high arched palate and malocclusion of teeth [1]. Furthermore, exercise-induced supraventricular tachycardia suggests cardiac involvement. The patient thus has to be classified as mitochondrial multiorgan disorder syndrome (MIMODS)

Clozapine for mitochondrial psychosis

cited By 1International audienceWith interest we read the article by Demily et al. about a 30 year old male with neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome due to the mutation m.8993TNC, clinically manifesting as cerebellar ataxia, pyramidal syndrome, and psychosis. Upon antipsychotic medication the patient developed dystonia, akathisia, and extrapyramidal symptoms with falls. Switching to clozapine resolved psychosis but triggered fatigue, myoclonus, and falls. We have the following comments and concern

ND2 mutation with minimal coenzyme-Q responsive manifestations

International audienceWith interest we read the article by Zanolini et al. about a 21 yo male with exercise-intolerance since age 7 y, recurrent vomiting since age 17 y, muscle wasting, decreased tendon reflexes, high-arched palate and mal-occlusion detected at age 20 y, exercise-induced supraventricular tachycardia, and lactic acidosis due to a ND2 mutation [1]. The patient profited from coenzyme-Q [1]. We have the following comments and concerns.We do not regard retinitis pigmentosa, polyneuropathy and hypoacusis as central nervous system features, as mentioned in the introduction. Additionally, there was not only muscle but also gastro-intestinal and cardiac involvement

Psychological morbidity in Leber’s hereditary optic neuropathy depends on phenotypic, social, economic, and genetic factors

Josef Finsterer,1 Sinda Zarrouk-Mahjoub2 1Krankenanstalt Rudolfstiftung, Vienna, Austria; 2University of Tunis El Manar, Genomics Platform, Pasteur Institute of Tunis, Tunis, Tunisia We have read with interest the article by Garcia et al1 about the effect of visual impairment on psychological well-being with regard to mood, interpersonal interactions, and career-related goals.1 Among the 103 Leber’s hereditary optic neuropathy (LHON) patients, half became depressed with negative impacts on interpersonal relations and career goals. At diagnosis, older age corresponded to higher depression prevalence than young age. We have the following comments and concerns.View the original paper by Garcia and colleagues. &nbsp

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

Josef Finsterer,1 Sinda Zarrouk-Mahjoub2 1Krankenanstalt Rudolfstiftung, Vienna, Austria; 2Genomics Platform, Pasteur Institute of Tunis, Tunisia 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. Keywords: mitochondrial DNA, heteroplasmy, respiratory chain, LHON, genotype–phenotype correlatio