Sporadic Bilateral Optic Neuropathy in Children: The Role of Mitochondrial Abnormalities

¹ Neurology Division, Cooper University Hospital, Camden, New Jersey, United States
² Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States
³ Radiology, University of Arkansas Medical Center, Little Rock, Arkansas, United States
⁴ Shafallah Genetics Center, Lusail Street, Doha, Central, Qatar

^* To whom correspondence should be addressed. E-mail: abuamero{at}gmail.com.

	Abstract

Purpose: To evaluate a group of patients with isolated, early-onset, bilateral optic neuropathy for genetic and biochemical evidence of mitochondrial disease. Design: Case Series Participants and Controls: 21 patients; 159 controls for mitochondrial (mt) DNA sequencing; 40 controls for relative mtDNA content. Methods: We identified patients with decreased vision since childhood due to bilateral optic neuropathy characterized by central visual loss with no other major neurologic or ocular abnormality and no clinical evidence of a mitochondrial syndrome. We performed clinical examination, electroretinograms, and neuroimaging; sequenced the entire mitochondrial DNA (mtDNA) coding region in leukocytes of all patients; assessed relative mtDNA content; and sequenced OPA1 and OPA3 nuclear genes associated with dominant and recessive optic atrophy, respectively. Main Outcome Measures: clinical description; non-synonymous (NS) mtDNA nucleotide changes; relative mtDNA content; OPA1 and OPA3 nucleotide changes Results: Twenty-one unrelated patients (16 male and 5 female; mean age at first examination 13.6 years) had bilateral moderate, relatively symmetric optic neuropathies and normal neurologic examinations other than strabismus in 11 and congenital nystagmus in nine. Four patients had optic nerve hypoplasia. One patient had the nt 11778 primary LHON mutation, and three others had mtDNA nucleotide changes predicted to be pathologic. The entire group had a small increase (6.7%) in relative mtDNA content of indeterminate statistical significance. No patient had a polymorphism or mutation of OPA1 or OPA3. Conclusions: A minority of these young patients with sporadic bilateral optic neuropathy had abnormalities of the mitochondrial parameters evaluated here. This bilateral optic neuropathy may be due to other genetic, epigenetic, or environmental injury to the optic nerve or to mitochondrial defects not studied.

Key Words: optic nerve, mitochondrial DNA, mutation, hypoplasia

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