녹내장으로 오인된 MT-TL1 유전자 변이 관련 비전형 레버유전시신경병증
A Case of Atypical Leber Hereditary Optic Neuropathy Associated with MT-TL1 Gene Mutation Misdiagnosed with Glaucoma
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목적: 레버유전시신경병증(Leber hereditary optic neuropathy, LHON)은 사립체 DNA의 돌연변이로 인해 발생하는 가장 흔한 유전성시신경병증 중 하나이다. LHON과 연관된 사립체 유전자의 변이는 m.3460, m.11778, m.14484 이 세 부위가 대표적으로 알려져 있다. 양안 시신경위축과 녹내장으로 진단된 환자에서 이전에 보고되지 않았던 mitochondrial tRNA (Leu [UUR]) 유전자(MT-TL1)의 변이(m.3268 A>G)를 발견하여 보고하는 바이다. 증례요약: 3년 전 지역안과에서 녹내장으로 진단 받았던 59세 여자 환자가 내원하였다. 초진 당시 최대교정시력은 우안 0.4, 좌안 0.7이었으며, 양안의 시신경위축이 있었다. 빛간섭단층촬영 검사에서 평균 망막시신경섬유층 두께는 우안 52 μm, 좌안 44 μm로 감소되어 있었으나, 시신경유두황반다발은 비교적 보존되어 있었다. 골드만시야계 검사에서 양안 주변부, 특히 상외측의 시야감소를 보였다. 유전자검사에서 사립체 DNA의 변이가 발견되었다. 결론: 저자들은 양안의 시신경위축이 있는 환자에서 이전에 보고되지 않았던 사립체 DNA의 새로운 변이(m.3268 A>G)를 발견하였다. MT-TL1 유전자의 변이로 인한 mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)와 영아기근병증은 이전에 보고된 적이 있지만, LHON이 유발된 사례는 처음이었다. MT-TL1 유전자의 변이와 관련된 본 증례의 LHON은 상대적으로 경미한 시력저하와 주변부 시야장애를 특징으로 하는 비전형적인 임상양상을 나타내었다.
Abstract
Purpose: Leber hereditary optic neuropathy (LHON) is one of the most common hereditary optic neuropathies caused by mutations of mitochondrial DNA. Three common mitochondrial mutations causing LHON are m.3460, m.11778, and m.14484. We report a rare mutation of the mitochondrial tRNA (Leu [UUR]) gene (MT-TL1) (m.3268 A > G) in a patient with bilateral optic atrophy. Case summary: A 59-year-old female diagnosed with glaucoma 3 years earlier at a community eye clinic presented to our neuro- ophthalmology clinic. On examination, her best corrected visual acuity was 0.4 in the right eye and 0.7 in the left eye, and optic atrophy was noticed in both eyes. Optical coherence tomography revealed retinal nerve fiber layer (RNFL) thinning in both eyes; average RNFL thickness was 52 μm in the right eye and 44 μm in the left eye, but the papillomacular bundle was relatively preserved in both eyes. Goldmann perimetry demonstrated peripheral visual field defects, mostly involving superotemporal visual field in both eyes. Mitochondrial DNA mutation test showed an unusual mutation in MT-TL1 gene seemingly related to this optic neuropathy. Conclusions: We found a rare mutation (m.3268 A > G) of the mitochondrial DNA in a patient having bilateral optic atrophy, which led to the diagnosis of LHON. There have been previous reports about mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and infantile myopathy caused by MT-TL1 mutation, but this is the first case of LHON associated with the same mutation. In this case of LHON associated with MT-TL1 mutation, atypical clinical features were observed with a relatively mild phenotype and peripheral visual field defects.
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