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Results for “Gyrate Atrophy”

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PubMed1985

Gyrate atrophy of choroid and retina complicated by vitreous hemorrhage.

We describe two patients with gyrate atrophy of the choroid and retina who suffered from vitreous hemorrhages in adolescence. The diagnosis of gyrate atrophy was confirmed biochemically and clinically; hyperornithinemia and a deficiency of ornithine ketoacid transaminase were confirmed biochemically. Typical fundus changes of scalloped chorioretinal atrophies with sharp margins, deteriorated dark adaptation, non-recordable electroretinogram, flat electrooculogram, and constricted visual fields were noted. We believe that the vitreous hemorrhage is an ocular complication in this disorder.

Adult↗

PubMed1989

Epiretinal membranes and cystoid macular edema in gyrate atrophy of the choroid and retina.

A 26-year-old woman with gyrate atrophy of the choroid and retina and hyperornithinemia lost central visual acuity because of cystoid macular edema associated with epiretinal membrane formation. Dietary manipulation over a 5-month interval reduced the plasma ornithine levels 37% but did not halt the progression of the gyrate atrophy nor influence the cystoid edema or visual acuity.

Adult↗

PubMed1981

Visual results of a long-term trial of a low-arginine diet in gyrate atrophy of choroid and retina.

Visual function has been serially assessed in two gyrate atrophy patients who have had long-term reduction of plasma ornithine concentrations by a low-arginine diet. One patient demonstrated subjective and objective improvement after 15 months of treatment. In addition to improvements in dark adaptation thresholds, enlargement of visual fields, and a more normal electroretinogram, there was marked improvement in cone function as measured by color vision. There has been no change noted in the second patient. These results suggest that reduction of plasma ornithine may be beneficial in gyrate atrophy patients and that the high ornithine concentrations characteristic of this disorder play some role in the pathophysiology.

Adult↗

PubMed2001

[Gyrate atrophy and craniopharyngioma: a case report].

We report the case of a 13-year-old girl who developed a craniopharyngioma and a gyrate atrophy. No genetic link between these two diseases has ever been reported. This case recalls the characteristic features of gyrate atrophy.

Adolescent↗

PubMed1999

Central nervous system involvement in gyrate atrophy of the choroid and retina with hyperornithinaemia.

In gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), a genetically determined deficiency of ornithine delta-aminotransferase activity leads to high ornithine concentrations in body fluids. GA is characterized by centripetally progressing retinal and choroidal destruction and selective atrophy with tubular aggregates in type II skeletal muscle fibres. These findings have been suggested to be mediated by hyperornithinaemia-induced deficiency of high-energy creatine phosphate. As abnormal brain magnetic resonance images and electroencephalograms are found in another disorder of creatine metabolism, guanidinoacetate methyltransferase deficiency, we investigated the central nervous system involvement in GA, which seems to be associated with a milder degree of phosphocreatine deficiency. We compared 23 untreated GA patients with age-matched healthy controls, and with 9 patients who had received creatine or creatine precursor supplementation daily for several years. The mean age of the patients (32 +/- 18 years) was similar to that of the controls (36 +/- 22 years). The MRI or EEG findings of the patients on creatine supplementation did not differ from those of the untreated group. Brain MRI revealed degenerative lesions in the white matter in 50% of the GA patients, and 70% of the patients had premature atrophic changes, with a striking increase in the number of Virchow's spaces. Of the patients whose EEG was recorded, 58% had abnormal slow background activity, focal lesions or high-amplitude beta rhythm (> 50 microV). The EEG findings were not associated with the MRI changes or with the age or the sex of the patients. Early degenerative and atrophic brain changes and abnormal EEG are thus features of GA, in addition to the well-characterized eye and muscle manifestations.

Adolescent↗

PubMed1981

Gyrate atrophy with hyperornithinaemia: different types of responsiveness to vitamin B6.

Three cases of Japanese patients with gyrate atrophy of the choroid and retina with hyperornithinaemia were studied clinically and biochemically. The types of disease differed in responsiveness to vitamin B6. In-vivo responsiveness to vitamin B6 was correlated with in-vitro data. It is suggested that the in-vitro examination of the influence of pyridoxal phosphate on ornithine ketoacid transaminase activity in cultured fibroblasts may be useful in ascertaining the efficacy of vitamin B6 treatment in gyrate atrophy. In addition the early development of the fundus lesions was observed in one case (case 1), and the ciliary body abnormality and chorioretinal atrophy were noted in another (case 3).

Adolescent↗

PubMed1983

Cataract in gyrate atrophy: clinical and morphologic studies.

The clinical appearance of the cataract in nine phakic patients with gyrate atrophy of the choroid and retina is described. The gross and microscopic examination of three cataractous lenses removed from patients 31 years to 47 years of age is reported. Clinically, the lens opacities appeared primarily along the confluence of the sutures posteriorly, interfering with vision because of their location in the visual axis. Histologically the region of the posterior sutures was filled with liquified and degenerated lens material typical of senile cataractous changes. By the second decade, cataract is a uniform finding in patients with gyrate atrophy and appears to be unique as compared with cataracts associated with other forms of retinal degeneration.

Adult↗

PubMed2004

Use of an arginine-restricted diet to slow progression of visual loss in patients with gyrate atrophy.

OBJECTIVE: To quantify the effect of long-term reduction of plasma ornithine levels through adherence to an arginine-restricted diet on visual function in patients of all ages with gyrate atrophy of the retina and choroid. METHODS: A long-term observational study was conducted on 27 patients with gyrate atrophy, 17 of whom elected to comply with the arginine-restricted diet and 10 who were unable to comply. The mean rates of change in the electroretinogram combined response, electroretinogram flicker response, and kinetic and static perimetry were determined. RESULTS: After mean follow-up of 13.9 years for the patients on the diet and 14.1 years for those not on the diet, the mean rates of change for the diet group compared with those of the no-diet group were statistically significantly slower for all outcome measures (age-adjusted P<.05) except for static perimetry (P =.06). CONCLUSIONS: Adhering to an arginine-restricted diet so as to lower the plasma ornithine level below an average of 5.29 to 6.61 mg/dL (400-500 micromol/L) will slow the loss of function as measured by sequential electroretinography and visual field examinations.

Adolescent↗

PubMed1980

Gyrate atrophy of the choroid and retina with hyperornithinemia. Deficient formation of guanidinoacetic acid from arginine.

Patients with gyrate atrophy of the choroid and retina have 10- to 20-fold increased ornithine concentrations in body fluids and significantly reduced activity of ornithine aminotransferase in lymphocytes and cultured fibroblasts. We administered intravenous arginine to six patients and six controls to study in vivo inhibition by high ornithine concentrations of arginine-glycine transamidinase, the rate-limiting enzyme in creatine synthesis. Serum arginine concentrations curves after administration were similar for the two groups. The increment in serum ornithine was more than three times as great in patients as in controls. The mean half-times in plasma ornithine were 360 and 97 min, respectively. In the patients, the metabolic clearance of ornithine from the extracellular fluid was significantly delayed. Urinary guanidinoacetate excretion rose markedly in all controls, the excretion rate being higher in females. The patients always excreted less than the controls, the differences within the sexes being highly significant. Differences in creatine excretion after administration were less marked. We conclude that in gyrate atrophy patients, formation of guanidinoacetate, creatine, and possibly phosphocreatine is inhibited at the transaminidation step by the high concentrations of ornithine. Deficiency of the high-energy phosphates may underlie the pathogenesis of the eye and muscle atrophies.

Adolescent↗

PubMed1985

Heterogeneity and complementation analysis of fibroblasts from vitamin B6 responsive and non-responsive patients with gyrate atrophy of the choroid and retina.

Fibroblasts from four pyridoxine responsive and three non-responsive patients with gyrate atrophy of the choroid and retina have been examined. Responsive patients had higher activity of ornithine ketoacid transaminase (OKT) in cell homogenates and greater incorporation of radioactivity from 14C-ornithine into protein in cultured cells in situ compared to non-responsive patients. Complementation analysis of the cells from these seven patients was performed, based on the ratio of incorporation of 14C/3H into protein in fused cells incubated in 14C-ornithine and 3H-leucine. Lack of positive complementation in these crosses suggests that pyridoxine responsive and non-responsive patients with gyrate atrophy represent different allelic mutations of the same genetic locus coding for OKT.

Atrophy↗

PubMed1991

Molecular pathology of gyrate atrophy of the choroid and retina due to ornithine aminotransferase deficiency.

Gyrate atrophy (GA) is an autosomal recessive eye disease characterized by progressive loss of vision due to chorioretinal degeneration. It is associated with a deficiency of the mitochondrial enzyme ornithine aminotransferase (OATase) with consequent hyperornithinemia. Although the clinical phenotype is largely confined to the eye, OATase deficiency is a systemic disorder. A step toward delineation of the enzyme defect in GA at the molecular level has been made by cloning and characterizing the cDNA and structural gene for OATase. The structural gene for OATase maps to chromosome 10 (10q26) and OATase-related sequences map to the X chromosome (Xp11.2). A diverse number of mutations at the OATase locus in GA patients of varied ethnic origins have been defined employing polymerase chain reaction and other molecular biological techniques. The majority of these mutations are of the missense type although a splicing mutation in one patient has recently been identified. The functional consequences of some of these mutations have been tested and confirmed in a eukaryotic expression system. These mutations demonstrate the allelic heterogeneity, which extends to both pyridoxine responsive and non-responsive forms of GA, reflecting the clinical and biochemical heterogeneity observed in this disease. The molecular studies in addition to providing information on the structure/function of the enzyme will facilitate understanding of the retinal pathophysiology in this disorder.

Base Sequence↗

PubMed1988

Gyrate atrophy of the choroid and retina: assignment of the ornithine aminotransferase structural gene to human chromosome 10 and mouse chromosome 7.

Gyrate atrophy of the choroid and retina is an autosomal recessive, blinding human disease caused by a deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT). Since human OAT cDNA hybridizes to DNA sequences on both human chromosomes 10 and X, a locus coding for OAT enzyme activity may be present on one or both of these human chromosomes. We have used a series of mouse-human somatic cell hybrids, in combination with starch gel electrophoresis and a histochemical stain for OAT enzyme activity, to assign the structural gene for OAT to human chromosome 10. Our results suggest that the human X chromosome does not contain a locus coding for OAT enzyme activity. In addition, we have used a panel of Chinese hamster-mouse hybrids to assign the murine Oat structural gene to mouse chromosome 7. Our findings, combined with recent molecular studies, indicate that human OAT probes specific for chromosome 10 will be useful for the diagnosis and genetic counseling of individuals at risk for gyrate atrophy.

Animals↗

PubMed1978

Ocular and biochemical abnormalities in gyrate atrophy of the choroid and retina.

Patients with gyrate atrophy of the choroid and retina have myopia, constricted visual fields, elevated dark adaptation thresholds, small or nondetectable ERGs, and chorioretinal atrophy. Biochemical abnormalities include hyperornithinemia, hypolysinemia, hyperornithinuria, an unknown amino compound in the urine, and virtual absence of OKT activity in extracts of cultured skin fibroblasts. Extracts of cultured skin fibroblasts from one patient studied in our laboratory showed an increase in OKT activity with increasing concentrations of vitamin B6 in the assay medium; this patient also showed some biochemical responsiveness within three weeks to 300 mg/day or orally administered vitamin B6. Three patients whose fibroblasts did not show increased OKT activity in vitro with increasing vitamin B6 did not respond in vivo to 300 mg/day of vitamin B6 over the same period. All four patients continue to be evaluated with larger doses of this vitamin. It remains to be established if long-term treatment with vitamin B6 will stabilize the course of the chorioretinal degeneration for at least some patients with this disease.

Administration, Oral↗

PubMed1989

At least two mutant alleles of ornithine delta-aminotransferase cause gyrate atrophy of the choroid and retina in Finns.

Gyrate atrophy of the choroid and retina (GA) is an inherited chorioretinal degeneration caused by deficiency of ornithine delta-aminotransferase (OAT; L-ornithine: 2-oxo-acid aminotransferase; EC 2.6.1.13). GA is one of the "Finnish genetic diseases," a group of several rare monogenic disorders that occur with increased frequency in the Finnish population. Using a combination of RNase A protection, genomic cloning, and polymerase chain reaction amplification of genomic DNA, we found one of two missense mutant OAT alleles to be present in each of 16 Finnish GA pedigrees. The first mutation R180T, in which arginine-180 is replaced by threonine, was present in homozygous form in patients from two pedigrees. The second mutation L402P, in which leucine-402 is replaced by proline, was present in homozygous form in patients from 14 pedigrees. Neither mutation was present in 19 Finnish controls. L402P was not present in 18 non-Finnish GA patients but R180T was found in an American GA patient. We constructed full-length mutant cDNAs by amplifying patient cDNA with the polymerase chain reaction and cloning a restriction fragment containing the mutation into an otherwise normal human OAT cDNA. These mutant cDNAs were then expressed in CHO-K1 cells, which lack endogenous OAT. Both R180T and L402P inactivate OAT. These results show molecular heterogeneity in GA alleles even in the Finnish population.

Alleles↗

PubMed1991

Gyrate atrophy of the choroid and retina in a 5-year-old girl.

A 5-year-old Asian-Indian female presented with bilateral cobblestone-like peripheral lesions, a single area of chorioretinal atrophy, infero-nasal to the disc, in her right eye and a non-recordable single flash ERG. Serum ornithine level was assayed at 841 mumol/l, ten times normal levels, and a diagnosis of gyrate atrophy, due to ornithine aminotransferase deficiency was made. The patient was refractory to any form of therapy and her clinical lesions spread rapidly in both eyes, showing both centrifugal and centripetal spread in her right eye. A rapid deterioration in her psychophysical tests was also seen over the 28 months follow-up. The presence of cobblestone-like peripheral lesions in a child should alert the clinician to the possibility of gyrate atrophy, and the rapid spread of the chorioretinal lesions coupled with non-recordable single flash ERGs, in a young patient may suggest a much poorer prognosis.

Child, Preschool↗

PubMed1978

Gyrate atrophy of the choroid and retina with reticular pigmentary dystrophy and ornithine-ketoacid-transaminase deficiency.

A 10 year old white girl is presented with gyrate atrophy of the choroid and retina (atrofia gyrata). She also showed reticular pigmentations at the level of the retinal pigment epithelium temporal to both maculas. A generalized hyperornithinaemia was demonstrated in this patient and cultured fibroblasts established the underlying ornithine-keto-acid-transaminase (OKT) deficiency for the first time. Pharmacologic doses of vitamin B6 nor restriction of dietary protein resulted in a significant decrease of the serum ornithine concentration. It is probable that hyperornithinaemia in itself is not the cause of the gyrate atrophy.

Adult↗

PubMed1983

[Gyrate atrophy of the choroid and retina with hyperornithinemia in an African family].

The authors report on a Kenyan family in which 4 of the 5 siblings were suffering from gyrate atrophy of the choroid and retina with hyperornithinemia. All the affected members of the family had myopia, hemeralopia, loss of vision and constricted visual fields but no cataract. To the authors' knowledge this is the first African family with gyrate atrophy to be reported.

Adolescent↗

PubMed1999

Muscle creatine phosphate in gyrate atrophy of the choroid and retina with hyperornithinaemia--clues to pathogenesis.

BACKGROUND: In gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), inherited deficiency of ornithine-o-aminotransferase leads to progressive fundus destruction and atrophy of type II skeletal muscle fibres. Because high ornithine concentrations inhibit creatine biosynthesis, the ensuing deficiency of high-energy creatine phosphate may mediate the pathogenesis. MATERIALS AND METHODS: Relative concentrations of inorganic phosphate (Pi), creatine phosphate (PCr) and ATP in resting calf muscle were recorded in 23 GA patients and 33 control subjects using 31P-magnetic resonance spectroscopy (MRS). Eight patients with autosomal recessive retinitis pigmentosa with matched control subjects constituted an additional reference group. RESULTS: The PCr/Pi and PCr/ATP ratios (means +/- SD) were lower for the GA patients than for healthy control subjects [4.66 +/- 0.37 vs. 9.75 +/- 2.17 (P < 0.0001) and 2.85 +/- 0.37 vs. 3.70 +/- 0.50 (P < 0.05) respectively]. In retinitis pigmentosa the respective values were 9.12 +/- 2.57 and 4.25 +/- 0.45. Age and stage of the disease had no effect. CONCLUSION: Muscle 31P-MRS spectra were markedly abnormal in all GA patients.

Adenosine Triphosphate↗