ARTICLE INFO

Article Type

Case Report

Authors

Daneshvar Kakhki   R. (* )






(* ) Neurology Department, Medical School, Kashan University of Medical Sciences, Kashan, Iran

Correspondence

Address: Neurology Ward, Shahid Beheshtei General Hospital, Kilometer 5 of Qotb-e-Ravandi Boulevard, Kashan, Iran
Phone: +98 (31) 55345455
Fax: +98 (31) 55345456
redaneshvar@gmail.com

Article History

Received:  June  28, 2016
Accepted:  January 30, 2017
ePublished:  March 25, 2017

BRIEF TEXT


Leber’s optic neuropathy was first introduced in 1871 by the German ophthalmologist, Theodor Leber (1840-1917) [1]. Leber disease is one of the most common mitochondrial genetic diseases in the northeast of England, with an estimated 1 in 25000 people [2]. The carriers of the gene of Leber disease are asymptomatic as long as they have vision blur in one eye. A large percentage of patients are involved with bilateral ophthalmic problem that this event occur in 25% of cases at the same time and in 75% of cases it occurs one after the other; the interval between involvement of two eyes is 8 weeks [3]. … [4, 5].

Previous studies have shown that carriers of the leber disease gene are asymptomatic until they cause a blur in one eye that this involvement occurs simultaneously in both eyes in 25% of cases and it occurs in two eyes one after another in the interval of 8 weeks in 75% of the cases [3].

The purpose of this article was to report a rare case of Leber`s disease, that the interval involvement between two eyes was outside the normal range and 11 years.

This research has been reported in the form of case and clinical study.

This study was conducted in 2014 on a 38-year-old man who was hospitalized in the Kashan Beheshti Hospital due to reduced vision of the left eye.

The patient was a 38-year-old man who was hospitalized in Kashan Beheshti hospital.

Patient eye examination showed visual acuity was in the level of perception of light in the right eye and fingers counts at distance of 20 cm in the left eye. The response of the pupil to direct and indirect light had been decreased, but the movements of the eye was normal. On the basis of ophthalmoscopy, the patient`s right eye disk was scratched and the left one was discolorated. Other systematic and neurological examinations were normal. Magnetic resonance imaging of the brain during admission and 11 years ago was normal. The total Visual Evoked Potential (VEP) of both eyes was not P100. Based on the results of fluorescein angiography, the visual nerve disk was pale without torsional or vascular obstruction. Experiments were negative for vasculitis and sarcoidosis. The patient was initially treated with pulsed methylprednisolone (1 gr for 3 consecutive days) with optic neuritis that no treatment response was seen after 2 weeks of treatment. Genetic studies were performed on peripheral blood cells using PCR technique and DNA limited degradation and direct sequencing, that homoplasmic mutation 14233 was diagnosed, and clinical suspicion of LHON was confirmed. The patient was treated with coenzyme Q10 100 mg/day and multivitamin and he was able to perceive objects at a distance of 70 cm from the left eye within 6 months of follow up.

The patient was initially treated with pulsed methylprednisolone (1 gr for 3 consecutive days) that after 2 weeks of treatment no treatment response was observed. Genetic studies on peripheral blood cells were performed using PCR technique, DNA limited degradation and direct sequencing that a homoplasmic mutation 14233 was diagnosed and clinical suspicion of LHON was confirmed. The patient was treated with coenzyme Q10 100 mg/day and received a multivitamin and within 6 months of follow up, he was able to perceive objects at distance of 70 cm with left eye.

The pattern of genetic transmission of this disease has been reported dominant autosomal, recessive autosomal, X linked and transmitted through mother. In 50% of the heredity cases, transmission occurs through the mother [6]. And in 50% of the patients, also, the results are of a new mutation (sporadic) [7]. In 90% of patients, one of the 4 mutations of 11778 (ND4), 14484 (ND6), 3460(ND1) or 14459 (ND6) has been reported in DNA mitochondria [8]. This last variant is responsible for musculoskeletal system (dystonia), along with visual analysis of the nerve [9]. In a study by a large group of Brazilian haplogroup patients (11778), Sadon et al. emphasized the role of environmental risk factors in the disease and identified the use of tobacco as the most common risk factor [10]. 85% of leber patients for mitochondrial DNA mutation are homoplasmy and the rest are heteroplasmy [11]. Heteroplasmic patients, with a higher rate of mitochondrial DNA mutation, are more likely to be blinded. Women who have mitochondrial DNA mutation up to 80%, have a lower risk for having boys with leber compared to homoplasmic women [12]. However, Hooponen rejects this issues because the level of heteroplasmy in the environmental blood cells with possibly different neurons [13]. … [14-19].

The genetic investigation is recommended for all men who visits the treatment centers with suspicion of MS due to visual disturbances and have peripapillary microangiopathy, especially if both of their eyes are involved or they have a positive family history of blindness.

There is no specific treatment for leber, and many patients with a diagnosis of neuropathy of the optic nerve have received high doses of pulse of methylprednisolone without any response.

Neuropathic diagnosis of leber optic nerve in young man with bilateral optic nerve disorder (usually one after the other and often within about 2 months) should be considered especially in those with a positive family history.

Thanks to Dr. Aghsabifar (neurothalmalogist, Farabi Hospital, Tehran), who collaborated with the patient`s ophthalmology assessments, and Dr. Sanati Laboratory of Genetics who approved the diagnosis of the disease with a genetic investigation.

There is no conflicts of interests.

The article has been published while obtaining written consent from the patient, without the name and with the approval of the University`s Ethics Council.

There is no budget for this article.


CITIATION LINKS

[1]Leber Th. Ueber hereditäre und congenital-angelegte Sehnervenleiden. Graefes Arch Clin Exp Ophthalmol. 1871;17(2):249-91. [Germany]
[2]Chinnery PF, Johnson MA, Wardell TM, Singh-Kler R, Hayes C, Brown DT, et al. The epidemiology of pathogenic mitochondrial DNA mutations. Ann Neurol. 2000;48(2):188-93.
[3]Harding AE, Sweeney MG, Govan GG, Riordan-Eva P. Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation. Am J Hum Genet 1995;57:77-86.
[4]Riordan-Eva P, Harding AE. Leber’s hereditary optic neuropathy: The clinical relevance of different mitochondrial DNA mutations. J Med Genet 1995;32(2):81-7.
[5]Nikoskelainen EK, Huoponen K, Juvonen V, Lamminen T, Nummelin K, Savontaus ML. Ophthalmologic findings in Leber hereditary optic neuropathy, with special reference to mtDNA mutations. Ophthalmol. 1996;103(3):504-14.
[6]Kerrison JB. Hereditary optic neuropathies. Ophthalmol Clin North Am. 2001;14(1):99-107.
[7]Yamada K, Mashima Y, Kigasawa K, Miyashita K, Wakakura M, Oguchi Y. High incidence of visual recovery among four Japanese patients with Leber's hereditary optic neuropathy with the 14484 mutation. J Neuroophthalmol. 1997;17(2):103-7.
[8]Johns DR, Berman J. Alternative, simultaneous complex I mitochondrial DNA mutations in Leber’s hereditary optic neuropathy. Biochem Biophys Res Commun. 1991;174(3):1324-30.
[9]Brown MD, Allen JC, Van Stavern GP, Newman NJ, Wallace DC. Clinical, genetic, and biochemical characterization of a Leber hereditary optic neuropathy family containing both the 11778 and 14484 primary mutations. Am J Med Genet. 2001;104(4):331-8.
[10]Sadun AA, Carelli V, Salomao SR, Berezovsky A, Quiros PA, Sadun F, et al. Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy. Am J Ophthalmol. 2003;136(2):231-8.
[11]Smith KH, Johns DR, Heher KL, Miller NR. Heteroplasmy in Leber’s hereditary optic neuropathy. Arch Ophthalmol 1993;111:1486-90
[12]Chinnery PF, Andrews RM, Turnbull DM, Howell NN. Leber hereditary optic neuropathy: Does heteroplasmy influence the inheritance and expression of the G11778A mitochondrial DNA mutation?. Am J Med Genet. 2001;98(3):235-43.
[13]Huoponen K. Leber hereditary optic neuropathy: Clinical and molecular genetic findings. Neurogenetics. 2001;3(3):119-25.
[14]Vanopdenbosch L, Dubois B, D'Hooghe MB, Meire F, Carton H. Mitochondrial mutations of Leber's hereditary optic neuropathy: A risk factor for multiple sclerosis. J Neurol. 2000;247(7):535-43.
[15]Pénisson-Besnier I, Moreau C, Jacques C, Roger JC, Dubas F, Reynier P. Multiple sclerosis and Leber's hereditary optic neuropathy mitochondrial DNA mutations. Rev Neurol (Paris). 2001;157(5):537-41. [French]
[16]Kalman B, Lublin FD, Alder H. Mitochondrial DNA mutations in multiple sclerosis. Mult Scler. 1995;1(1):32-6.
[17]Mojon DS, Herbert J, Sadiq SA, Miller JR, Madonna M, Hirano M. Leber's hereditary optic neuropathy mitochondrial DNA mutations at nucleotides 11778 and 3460 in multiple sclerosis. Ophthalmologica. 1999;213(3):171-5.
[18]Mashima Y, Kigasawa K, Wakakura M, Oguchi Y. Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy? J Neuroophthalmol. 2000;20(3):166-70.
[19]Nakamura M, Yamamoto M. Variable pattern of visual recovery of Leber's hereditary optic neuropathy. Br J Ophthalmol. 2000;84(5):534-5.