This case emphasises the importance of correct diagnosis, family screening and early treatment in GA of the choroid as it slows down the progression of retinal degeneration and prevents complications of the disease. Human hereditary deficiency of ornithine aminotransferase activity is transmitted as an autosomal recessive trait,3
and results in a 10-fold to 20-fold increased level of plasma ornithine and is shown to be associated with GA.4
The initial complaint of decreasing visual acuity and night vision is followed by the appearance of sharply demarcated, circular areas of chorioretinal atrophy with hyper pigmented margins in the mid periphery of the fundus. This appears through the first three decades of life and leads to blindness in the fourth to seventh decades. Myopia, posterior subcapsular cataracts and vitreous opacities may also be present.5
GA is a genetic disorder with increased frequency in the Finnish population with an incidence of one case per 50 000 individuals in Finland.5
Valle and Simell in a review in 2001 revealed that among over 150 biochemically documented cases of GA, about one-third of them were from Finland and only 7 of them (less than 5%) had been responsive to treatment with vitamin B6
We report rare cases of GA, in which the patient's high level of serum ornithine was responsive to treatment with a vitamin B6
dietary supplement. Weleber and Kennaway in a clinical trial of vitamin B6
for GA reported that three out of seven patients responded to oral B6
supplementation with over 50% reduction of serum ornithine.7
Among approximately 70 Finnish GA cases reported to date, none has been responsive to vitamin B6
Of the remaining studies reported worldwide (from USA, Canada, Japan, Italy, Germany, The Netherlands and Israel) only seven have been reported to have responded to vitamin B6
McCulloch and Marliss demonstrated that ornithine was being released from many organ systems and suggested multisystem involvement.10
Takki first reported that abnormal EEG recordings and borderline low intellectual function were common in GA.11
One of our patients also had abnormal EEG with no muscle wasting; thus, favouring multisystem involvement in GA of the choroid. Long-term treatment with certain anticonvulsants (phenytoin, succinimide) cause reduced plasma levels of pyridoxine,12
but our patient was on sodium valproate which itself does not cause pyridoxine deficiency. Our patients fulfil the diagnostic criteria of GA of the choroid, which include: typical gyrate retinal and choroidal lesions, early cataract, high myopia with marked astigmatism, hyperornithinaemia and autosomal recessive inheritance pattern.
The visual fields coincide fairly well with the remaining area of healthy appearing retina (about 15–50 °) with an enlarged blind spot corresponding to the peri papillary lesion if present. Our patients showed constricted visual fields in both their eyes. GA of the choroid has been reported in patients around the world of different ethnic origin.13 14
Our patients belong to a Thakali community (one of the ethnic groups in Nepal). The proposed treatment for GA is to correct one or more metabolic alterations like hyperornithinaemia, creatine deficiency, lysine deficiency and P5C/proline deficiency. The administration of pharmacological doses of pyridoxine in a disorder caused by decreased activity of a B6
-dependent enzyme is an established procedure.15
The advantage of pyridoxine supplementation is that it is an easy treatment and, consequently, patient compliance is good. In addition, Weleber and co-workers reported that B6
-responsive patients typically have a milder course of disease compared to B6
non-responsive patient in terms of visual function as well as less extensive lesions.16
By controlling the arginine intake in the diet, a desired plasma ornithine level can be achieved. One protocol called for 0.5 g protein/kg/day with 0.3–0.5 g Essential Amino Acids (EAA)/kg/day.17
The major reported risk in arginine-restriction treatment is that if the arginine restriction is carried to excess, both arginine and ornithine levels may become depleted with resultant impairment of urea cycle function and consequent hyperammonaemia.18
Both our patients responded well to pyridoxine intake and tolerated a restricted protein diet. Correction of lysine deficiency, creatine deficiency and proline deficiency is also recommended but clinical results of such treatment over the long-term are needed.
- Early diagnosis and treatment of GA of the choroid prevents the visual and life-threatening complications of disease.
- Confusion in diagnosis is primarily due to the rarity of the disease. Correct clinical diagnosis with confirmation by biochemical investigations of this rare disease should be done.
- Screening of the family members is important as GA of the choroid follows an autosomal recessive inheritance pattern.