<b><i>OPA3</i></b>-Related Autosomal Dominant Optic Atrophy and Cataract with Ataxia and Areflexia

atrophy and nystagmus since the first year of life, (2) progressive loss of vision, and (3) bilateral cerulean cataract at age 37. Additional symptoms consisted of intractable constipation alternating with severe diarrhea since childhood, together with gait unsteadiness, paresthesias in the four extremities, cramps, and burning pain in the lower limbs since the age of 35. Clinical examination at the age of 38 showed cerebellar ataxia, lower limb areflexia, pinprick and light-touch hypoesthesia, and pes cavus. Ophthalmological examination showed a visual acuity of 1/10 in both eyes. Eye fundus examination disclosed bilateral optic atrophy. Goldmann visual field examination revealed bilateral central scotoma, and slit-lamp examination showed bilateral cerulean cataract. Electroretinography was normal and visual-evoked potentials showed bilateral optic nerve dysfunction. Motor as well as sensory nerve conduction studies, myography, and motor-evoked potentials were all normal. Somatosensory-evoked potentials disclosed prolonged latencies of cortical as well as lumbar potentials. Brain MRI only showed mild cerebellar atrophy and MR spectroscopy was normal. Blood tests including serum lactate and pyruvate concentrations were normal. Dear Sir, Hereditary optic atrophies refer to a heterogeneous group of genetic disorders in which the most common form is autosomal dominant optic atrophy (ADOA). Only two genes, i.e. OPA1 and OPA3, have been identified in ADOA so far [1–3] . Mutations in OPA1 are responsible for 60– 80% of familial cases of ADOA while OPA3 has been implicated in only two families with ADOA and associated cataract (ADOAC) [2, 3] . Additional neurological signs have been reported in about 20% of OPA1mutated patients and have also been described in some OPA3mutated patients [2, 3] . Recessive mutations in OPA3 are responsible for type III 3-methylglutaconic aciduria (the so-called Costeff syndrome) consisting of early-onset bilateral optic atrophy, spasticity, extrapyramidal signs, and cognitive deficit [4] . Here we describe a third family harboring a dominant mutation in OPA3 responsible for ADOAC with additional neurological features. Ophthalmological signs of this 38-yearold woman consisted of (1) bilateral optic Received: March 20, 2012 Accepted: May 6, 2012 Published online: July 10, 2012