Gyrate atrophy: clinical and genetic findings in a female without arginine-restricted diet during her first 39 years of life and report of a new OAT gene mutation

Abstract

We report the clinical and genetic data obtained at a 17-year follow-up examination of a patient with gyrate atrophy, without an arginine-restricted diet. Patient examinations included visual acuity (VA), perimetry, biomicroscopy, funduscopy, fundus photography, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (OCT), and standard full-field electroretinography (ERG). Blood samples were taken for measurement of serum ornithine level and molecular genetic analysis of the OAT gene. The female was 22 years of age when gyrate atrophy was diagnosed based on peripheral chorioretinal atrophy and an increased ornithine level. Reexamination after 17 years revealed a reduced VA (0.25 OU), dense cataract, extensive peripheral chorioretinal atrophy, a further increased ornithine level, but only slow progression of visual field constriction, and still detectable ERG amplitudes. FAF was absent in the atrophic periphery and almost homogeneous at the posterior pole except parafoveally. OCT showed interruption of the foveal inner/outer segment junction and parafoveal microcystoid spaces. After cataract surgery, VA increased to the same values as those found at the age of 22 years (0.5 OD, 0.6 OS). Molecular analysis revealed a new deletion c.532_536delTGGGG (p.Trp178X) and a known mutation c.897C>G (p.Tyr299X) in the OAT gene. Although the patient had refused to diet during her first 39 years of life, the gyrate atrophy showed a very slow progression. FAF allows evaluating the integrity of the retinal pigment epithelium and may help to delimit gyrate atrophy from choroideremia. Interruption of foveal inner/outer segment junction and cystoid macula edema appears in gyrate atrophy.

Progression of gyrate atrophy measured with ultra-wide-field imaging

“…The natural course of gyrate atrophy in a patient with unrestricted diet has been previously reported [17]. The patient could not comply with a low-arginine diet during her first 39 years of life.…”

“…FAF showed a homogeneous autofluorescence at the posterior pole with preserved RPE, with mild speckled changes of the fovea. OCT changes include interruption of foveal inner/outer segment junction and cystoid macular edema [17,19].…”

Gyrate Atrophy in 2 Siblings – Ophthalmological Findings and A New Mutation

“…OTC = ornithine transcarbamylase. Black bar = enzymatic blockpatient with a very mild progress even without dietary treatment for her first 39 years of life is described[6]. In our patient, one month after initiation of dietary therapy with a defined amount of protein plasma concentration of ornithine is not yet sufficiently reduced (636 µmol/l) ( • ▶Fig.…”

Clinical Heterogeneity in Autosomal Recessive Bestrophinopathy with Biallelic Mutations in the BEST1 Gene

“…Fundus photography was obtained with either digital fundus photography, Optos ® wide-angle two-wavelengths reflectance imaging (Optos Plc, Dunfermline, Scotland), or three-wavelengths reflectance imaging (MultiColor ® , Heidelberg Engineering, Heidelberg, Germany). Fundus autofluorescence (FAF, 486/488 nm excitation) and near-infrared reflectance images (NIR, 815 nm) were obtained with a Heidelberg Retina Angiograph HRA1 or SPECTRALIS ® HRA (Heidelberg Engineering, Heidelberg, Germany) as described in detail previously [39,40]. Optical coherence tomography (OCT) was obtained with SPECTRALIS ® Spectral domain-OCT (Heidelberg Engineering) except for patient #8 (Swept-source OCT, Zeiss Plex Elite 9000 ® , Carl Zeiss Jena, Jena, Germany).…”