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Middle-aged Woman With Bilateral Macular Atrophy, Hearing Loss, and Headache

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 45-year-old woman was referred to the medical retina service for evaluation of bilateral macular atrophy noted by her general ophthalmologist. Medical history was positive for bilateral sensorineural hearing loss with cochlear origin as determined by an otolaryngologist and headache since age 35 years. She had no history of longer-term use of medications. There was no family history of hearing and vision loss in all immediate family members. Her best-corrected visual acuity was 20/20 OD and 20/63 OS. Her pupils were round and reactive. The anterior segment was unremarkable. Fundus examination confirmed the presence of bilateral macular atrophy. Fundus autofluorescence revealed a fairly symmetric loss of autofluorescence in the macula and in the regions surrounding the optic disc (Figure). In proximity of these areas of reduced autofluorescence, a speckled fundus autofluorescence pattern of alternating spots of increased and decreased autofluorescence was also noted. Optical coherence tomography displayed the presence of a bilateral atrophy of the outer retina and retinal pigment epithelium (Figure). The patient’s family underwent a complete ophthalmologic evaluation, which did not display any alteration.

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Mitochondrial encephalopathy with lactic acidosis and strokelike episodes–related syndrome

C. Genetic testing to rule out a mitochondrial disease

Macular atrophy may represent the clinical outcome of different disorders sharing some overlap in the biological pathways. While age-related macular degeneration is the most common disorder associated with macular atrophy, macular atrophy may be also the result of medications-associated retinal toxicity, ocular inflammation, and genetically determined retinal dystrophies. A detailed collection of medical and family history is mandatory as initial workup in cases of macular atrophy.

Mitochondrial encephalopathy with lactic acidosis and strokelike episodes syndrome (MELAS) represents a clinical entity associated with mitochondrial dysfunction.1,2 As with other mitochondrial disorders, MELAS is maternally inherited and is characterized by incomplete penetrance.13 MELAS is due to mitochondrial DNA (mtDNA) mutations. Specifically, the MT-TL1 mitochondrial gene (OMIM 590050) is the most frequently mutated and, in particular, the most frequent is the point mutation m.3243A>G/MT-TL1.4,5 Besides the full-blown MELAS,1,2 this disorder may have variable clinical expressivity with a broad spectrum of manifestations.4,5 This variability is partially related to the phenomenon of heteroplasmy, defined as the coexistence of wild-type and mutated mtDNA copies in the same cell. As distinct cells and tissues may have different heteroplasmy percentages, the phenotypic expression may vary among patients.610

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Article Information

Corresponding Author: Giuseppe Querques, MD, PhD, Department of Ophthalmology, University Vita-Salute San Raffaele, Via Olgettina 60, Milan, Italy (giuseppe.querques@hotmail.it).

Published Online: September 9, 2021. doi:10.1001/jamaophthalmol.2021.0944

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

References
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Pavlakis  SG , Phillips  PC , DiMauro  S , De Vivo  DC , Rowland  LP .  Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.   Ann Neurol. 1984;16(4):481-488. PubMedGoogle ScholarCrossref
2.
Goto  Y , Nonaka  I , Horai  S .  A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies.   Nature. 1990;348(6302):651-653. PubMedGoogle ScholarCrossref
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La Morgia  C , Maresca  A , Caporali  L , Valentino  ML , Carelli  V .  Mitochondrial diseases in adults.   J Intern Med. 2020;287(6):592-608. PubMedGoogle ScholarCrossref
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Mancuso  M , Orsucci  D , Angelini  C ,  et al.  The m.3243A>G mitochondrial DNA mutation and related phenotypes.   J Neurol. 2014;261(3):504-510. PubMedGoogle ScholarCrossref
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Brandon  MC , Lott  MT , Nguyen  KC ,  et al.  MITOMAP: a human mitochondrial genome database.   Nucleic Acids Res. 2005;33(Database issue):D611-D613. PubMedGoogle ScholarCrossref
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7.
Massin  P , Virally-Monod  M , Vialettes  B ,  et al; GEDIAM Group.  Prevalence of macular pattern dystrophy in maternally inherited diabetes and deafness.   Ophthalmology. 1999;106(9):1821-1827. PubMedGoogle ScholarCrossref
8.
Sue  CM , Mitchell  P , Crimmins  DS , Moshegov  C , Byrne  E , Morris  JGL .  Pigmentary retinopathy associated with the mitochondrial DNA 3243 point mutation.   Neurology. 1997;49(4):1013-1017. PubMedGoogle ScholarCrossref
9.
Rummelt  V , Folberg  R , Ionasescu  V , Yi  H , Moore  KC .  Ocular pathology of MELAS syndrome with mitochondrial DNA nucleotide 3243 point mutation.   Ophthalmology. 1993;100(12):1757-1766. PubMedGoogle ScholarCrossref
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de Laat  P , Smeitink  JAM , Janssen  MCH , Keunen  JEE , Boon  CJF .  Mitochondrial retinal dystrophy associated with the m.3243A>G mutation.   Ophthalmology. 2013;120(12):2684-2696. PubMedGoogle ScholarCrossref
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