title: Leber's Hereditary Optic Neuropathy (LHON) with 14484/ND6 mutation in a North African patient.
abstract: We report the clinical and genetic study of a Leber's Hereditary Optic Neuropathy (LHON) patient of North African origin harboring the 14484/ND6 mutation of mtDNA. For over a year we followed the ophthalmological course of this 24-year-old male with LHON treated with idebenone and vitamin B12. Serum lactate after effort was evaluated before, during and after therapy. Muscle biopsy was obtained for morphological study. Homo/heteroplasmy of 14484/ND6 mutation was studied in different tissues. Recovery of visual acuity was documented 6 months after onset and 3 months after therapy was established. Baseline serum lactate was elevated but normalized after 3.5 months of therapy. Muscle biopsy demonstrated only a few fibers with a slightly increased subsarcolemmal SDH activity. Genetic analysis showed homoplasmic 14484/ND6 mutation in all tissues investigated. The clinical phenotype of LHON/14484 in this patient closely resembles that commonly found in European patients. Even if LHON/14484 patients are reported to have a better prognosis for visual recovery, it is possible that the evolution of visual recovery in this patient could have been influenced by therapy as suggested by changes in serum lactate levels. Bioenergetic impairment of skeletal muscle was documented by lactate levels and muscle morphology. The 14484/ND6 mutation behaves as a primary mutation regardless of mtDNA population-specific backgrounds.
authors.affiliation: Institute of Neurology, University of Bologna, Italy. genetica@neuro.unibo.it
authors.forename: V
authors.initials: V
authors.lastname: Carelli
authors.forename: P
authors.initials: P
authors.lastname: Barboni
authors.forename: A
authors.initials: A
authors.lastname: Zacchini
authors.forename: R
authors.initials: R
authors.lastname: Mancini
authors.forename: L
authors.initials: L
authors.lastname: Monari
authors.forename: S
authors.initials: S
authors.lastname: Cevoli
authors.forename: R
authors.initials: R
authors.lastname: Liguori
authors.forename: M
authors.initials: M
authors.lastname: Sensi
authors.forename: E
authors.initials: E
authors.lastname: Lugaresi
authors.forename: P
authors.initials: P
authors.lastname: Montagna
mesh_terms: D000328:Adult; D000352:Africa, Northern; D001707:Biopsy, Needle; D004272:DNA, Mitochondrial / Q000032:analysis; D003576:Electron Transport Complex IV / Q000032:analysis; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D015418:Optic Atrophies, Hereditary / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012607:Scotoma / Q000150:complications / Q000175:diagnosis; D017422:Sequence Analysis, DNA; D019966:Substance-Related Disorders / Q000150:complications; D013385:Succinate Dehydrogenase / Q000032:analysis
chemical_list: D004272:DNA, Mitochondrial; D019344:Lactic Acid; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV