Top

Published in:

01-08-2012 | Original Research Article

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

Authors: Agnes B. Renner, Andreas Walter, Britta S. Fiebig, Herbert Jägle

Published in: Documenta Ophthalmologica | Issue 1/2012

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.

Valle D, Simell O (2001) The hyperornithinaemias. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 1857–1895

Mitchell GA, Looney JE, Brody LC, Steel G, Suchanek M, Engelhardt JF, Willard HF, Valle D (1988) Human ornithine-delta-aminotransferase. cDNA cloning and analysis of the structural gene. J Biol Chem 263:14288–14295PubMed

Ramesh V, Benoit LA, Crawford P, Harvey PT, Shows TB, Shih VE, Gusella JF (1988) The ornithine aminotransferase (OAT) locus: analysis of RFLPs in gyrate atrophy. Am J Hum Genet 42:365–372PubMed

Wu J, Ramesh V, Kidd JR, Castiglione CM, Myers S, Carson N, Anderson L, Gusella JF, Simpson NE, Kidd KK (1988) The ornithine aminotransferase (OAT) locus is linked and distal to D10S20 on the long arm of chromosome 10. Cytogenet Cell Genet 48:126–127PubMedCrossRef

Rao GN, Cotlier E (1984) Ornithine delta-aminotransferase activity in retina and other tissues. Neurochem Res 9:555–562PubMedCrossRef

Ratzlaff K, Baich A (1987) Comparison of ornithine aminotransferase activities in the pigment epithelium and retina of vertebrates. Comp Biochem Physiol B 88:35–37PubMedCrossRef

Bernstein SL, Wong P (1998) Regional expression of disease-related genes in human and monkey retina. Mol Vis 4:24PubMed

O’Donnell JJ, Sandman RP, Martin SR (1978) Gyrate atrophy of the retina: inborn error of L-ornithin: 2-oxoacid aminotransferase. Science 200:200–201PubMedCrossRef

Simell O, Takki K (1973) Raised plasma-ornithine and gyrate atrophy of the choroid and retina. Lancet 1:1031–1033PubMedCrossRef

10.

Takki K, Simell O (1974) Genetic aspects in gyrate atrophy of the choroid and retina with hyperornithinaemia. Br J Ophthalmol 58:907–916PubMedCrossRef

11.

Takki K (1974) Gyrate atrophy of the choroid and retina associated with hyperornithinaemia. Br J Ophthalmol 58:3–23PubMedCrossRef

12.

Vannas-Sulonen K, Sipila I, Vannas A, Simell O, Rapola J (1985) Gyrate atrophy of the choroid and retina. A five-year follow-up of creatine supplementation. Ophthalmology 92:1719–1727PubMed

13.

Kaiser-Kupfer MI, de Monasterio FM, Valle D, Walser M, Brusilow S (1980) Gyrate atrophy of the choroid and retina: improved visual function following reduction of plasma ornithine by diet. Science 210:1128–1131PubMedCrossRef

14.

Kaiser-Kupfer MI, de Monasterio F, Valle D, Walser M, Brusilow S (1981) Visual results of a long-term trial of a low-arginine diet in gyrate atrophy of choroid and retina. Ophthalmology 88:307–310PubMed

15.

Kaiser-Kupfer MI, Caruso RC, Valle D (1991) Gyrate atrophy of the choroid and retina. Long-term reduction of ornithine slows retinal degeneration. Arch Ophthalmol 109:1539–1548PubMedCrossRef

16.

Kaiser-Kupfer MI, Caruso RC, Valle D (2002) Gyrate atrophy of the choroid and retina: further experience with long-term reduction of ornithine levels in children. Arch Ophthalmol 120:146–153PubMedCrossRef

17.

Kaiser-Kupfer MI, Caruso RC, Valle D, Reed GF (2004) Use of an arginine-restricted diet to slow progression of visual loss in patients with gyrate atrophy. Arch Ophthalmol 122:982–984PubMedCrossRef

18.

Valle D, Walser M, Brusilow SW, Kaiser-Kupfer M (1980) Gyrate atrophy of the choroid and retina: amino acid metabolism and correction of hyperornithinaemia with an arginine-deficient diet. J Clin Invest 65:371–378PubMedCrossRef

19.

Valle D, Walser M, Brusilow S, Kaiser-Kupfer MI, Takki K (1981) Gyrate atrophy of the choroid and retina. Biochemical considerations and experience with an arginine-restricted diet. Ophthalmology 88:325–330PubMed

20.

Weleber RG, Kennaway NG, Buist NR (1981) Gyrate atrophy of the choroid and retina. Approaches to therapy. Int Ophthalmol 4:23–32PubMedCrossRef

21.

Santinelli R, Costagliola C, Tolone C, D’Aloia A, D’Avanzo A, Prisco F, Perrone L, del Giudice EM (2004) Low-protein diet and progression of retinal degeneration in gyrate atrophy of the choroid and retina: a twenty-six-year follow-up. J Inherit Metab Dis 27:187–196PubMedCrossRef

22.

Weleber RG (2006) Gyrate atrophy of the choroid and retina. In: Heckenlively JR, Arden GB (eds) Principles and practice of clinical electrophysiology of vision. The MIT Press, Cambridge, pp 705–715

23.

McCulloch C, Marliss EB (1975) Gyrate atrophy of the choroid and retina: clinical, ophthalmologic, and biochemical considerations. Trans Am Ophthalmol Soc 73:153–171PubMed

24.

Takki KK, Milton RC (1981) The natural history of gyrate atrophy of the choroid and retina. Ophthalmology 88:292–301PubMed

25.

Kaiser-Kupfer M, Kuwabara T, Uga S, Takki K, Valle D (1983) Cataract in gyrate atrophy: clinical and morphologic studies. Invest Ophthalmol Vis Sci 24:432–436PubMed

26.

Oliveira TL, Andrade RE, Muccioli C, Sallum J, Belfort R Jr (2005) Cystoid macular edema in gyrate atrophy of the choroid and retina: a fluorescein angiography and optical coherence tomography evaluation. Am J Ophthalmol 140:147–149PubMedCrossRef

27.

Vasconcelos-Santos DV, Magalhaes EP, Nehemy MB (2007) Macular edema associated with gyrate atrophy managed with intravitreal triamcinolone: a case report. Arq Bras Oftalmol 70:858–861PubMedCrossRef

28.

Marmor MF, Fulton AB, Holder GE, Miyake Y, Brigell M, Bach M (2009) ISCEV Standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol 118:69–77PubMedCrossRef

29.

Peltola KE, Nanto-Salonen K, Heinonen OJ, Jaaskelainen S, Heinanen K, Simell O, Nikoskelainen E (2001) Ophthalmologic heterogeneity in subjects with gyrate atrophy of choroid and retina harboring the L402P mutation of ornithine aminotransferase. Ophthalmology 108:721–729PubMedCrossRef

30.

Kaiser-Kupfer MI, Valle D, Bron AJ (1980) Clinical and biochemical heterogeneity in gyrate atrophy. Am J Ophthalmol 89:219–222PubMed

31.

Hayasaka S, Shiono T, Mizuno K, Sasayama C, Akiya S, Tanaka Y, Hayakawa M, Miyake Y, Ohba N (1986) Gyrate atrophy of the choroid and retina: 15 Japanese patients. Br J Ophthalmol 70:612–614PubMedCrossRef

32.

Kaiser-Kupfer MI, Ludwig IH, de Monasterio FM, Valle D, Krieger I (1985) Gyrate atrophy of the choroid and retina. Early findings. Ophthalmology 92:394–401PubMed

33.

Raitta C, Carlson S, Vannas-Sulonen K (1990) Gyrate atrophy of the choroid and retina: ERG of the neural retina and the pigment epithelium. Br J Ophthalmol 74:363–367PubMedCrossRef

34.

Caruso RC, Nussenblatt RB, Csaky KG, Valle D, Kaiser-Kupfer MI (2001) Assessment of visual function in patients with gyrate atrophy who are considered candidates for gene replacement. Arch Ophthalmol 119:667–669PubMed

35.

Vannas-Sulonen K (1987) Progression of gyrate atrophy of the choroid and retina. A long-term follow-up by fluorescein angiography. Acta Ophthalmol (Copenh) 65:101–109CrossRef

36.

Feldman RB, Mayo SS, Robertson DM, Jones JD, Rostvold JA (1989) Epiretinal membranes and cystoid macular edema in gyrate atrophy of the choroid and retina. Retina 9:139–142PubMedCrossRef

37.

Renner AB, Kellner U, Cropp E, Preising MN, MacDonald IM, van den Hurk JA, Cremers FP, Foerster MH (2006) Choroideremia: variability of clinical and electrophysiological characteristics and first report of a negative electroretinogram. Ophthalmology 113:2066 e2061–2010

38.

Renner AB, Fiebig BS, Cropp E, Weber BH, Kellner U (2009) Progression of retinal pigment epithelial alterations during long-term follow-up in female carriers of choroideremia and report of a novel CHM mutation. Arch Ophthalmol 127:907–912PubMedCrossRef

39.

Preising MN, Wegscheider E, Friedburg C, Poloschek CM, Wabbels BK, Lorenz B (2009) Fundus autofluorescence in carriers of choroideremia and correlation with electrophysiologic and psychophysical data. Ophthalmology 116(1201–1209):e1201–e1202CrossRef

40.

Poloschek CM, Kloeckener-Gruissem B, Hansen LL, Bach M, Berger W (2008) Syndromic choroideremia: sublocalization of phenotypes associated with Martin-Probst deafness mental retardation syndrome. Invest Ophthalmol Vis Sci 49:4096–4104PubMedCrossRef

41.

Mashima Y, Murakami A, Weleber RG, Kennaway NG, Clarke L, Shiono T, Inana G (1992) Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy. Am J Hum Genet 51:81–91PubMed

42.

Dietz HC, Valle D, Francomano CA, Kendzior RJ Jr, Pyeritz RE, Cutting GR (1993) The skipping of constitutive exons in vivo induced by nonsense mutations. Science 259:680–683PubMedCrossRef

Title: 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
Authors: Agnes B. Renner
Andreas Walter
Britta S. Fiebig
Herbert Jägle
Publication date: 01-08-2012
Publisher: Springer-Verlag
Published in: Documenta Ophthalmologica / Issue 1/2012
Print ISSN: 0012-4486
Electronic ISSN: 1573-2622
DOI: https://doi.org/10.1007/s10633-012-9335-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2012

Analysis of multifocal electroretinograms from a population with type 1 diabetes using partial least squares reveals spatial and temporal distribution of changes to retinal function

Reproducibility of multifocal VEP latency using different stimulus presentations

Clinical and electrophysiological recovery in Leber hereditary optic neuropathy with G3460A mutation

A case of bilateral, acquired, and acute dysfunction of short-wavelength-sensitive cone systems

Bilateral paraneoplastic optic neuropathy and unilateral retinal compromise in association with prostate cancer: a differential diagnostic challenge in a patient with unexplained visual loss

Evaluation of multifocal visual evoked potentials in patients with Graves’ orbitopathy and subclinical optic nerve involvement