Lysine in Treatment of Hyperornithinemia

Giordano, Claudio; Santo, Natale G. De; Pluvio, M; Santinelli, R; Stoppoloni, G

doi:10.1159/000181428

Cited by 16 publications

(7 citation statements)

References 11 publications

(19 reference statements)

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“…Unfortunately, the long term consequences of pyridoxine treatment in these patients have not been described. Several other experimental treatments, including supplementation with creatine or proline, failed to show unequivocal efficacy (21)(22)(23)(24). Attempts at correcting ornithine accumulation by dietary reduction of its precursor, arginine, have been described in several studies (Fig.…”

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confidence: 99%

Correction of ornithine accumulation prevents retinal degeneration in a mouse model of gyrate atrophy of the choroid and retina

Wang

Steel

Milam

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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Deficiency of ornithine-␦-aminotransferase (OAT) in humans results in gyrate atrophy of the choroid and retina (GA), an autosomal recessive disorder characterized by ornithine accumulation and a progressive chorioretinal degeneration of unknown pathogenesis. To determine whether chronic, systemic reduction of ornithine can prevent this form of retinal degeneration, we used an argininerestricted diet to maintain long term reduction of ornithine in a mouse model of OAT-deficiency (Oat ؊͞؊ ) produced by gene targeting. We evaluated the mice over a 12-month period by measurement of plasma amino acids, electroretinograms, and retinal histologic and ultrastructural studies. We found that an argininerestricted diet substantially reduces plasma ornithine levels and completely prevents retinal degeneration in Oat ؊͞؊ . This result indicates that ornithine accumulation is a necessary factor in the pathophysiology of the retinal degeneration in GA and that restoration of OAT activity in retina is not required for effective treatment of GA.

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confidence: 99%

Correction of ornithine accumulation prevents retinal degeneration in a mouse model of gyrate atrophy of the choroid and retina

Wang

Steel

Milam

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…Care must also be taken to avoid negative nitrogen balance, which occurred in one child when the daily protein intake was 1 g/kg or less (11). Addition of non-essential nitrogen to the diet corrected this problem.…”

Section: Restriction Of Diefary Substrates or Precursorsmentioning

confidence: 99%

“…Glutamate, proline and lysine supplements have been suggested as possible treatment for gyrate atrophy although only the last has been tried (11,13,16,57). Acute lysine loads increase plasma lysine levels and the excretion of lysine and ornithine in the urine.…”

Section: Replacement Of Dejicient Productsmentioning

confidence: 99%

“…In one study five patients were given 4 g/day of lysine in addition to their regular diets over a period of one month with no effect on plasma ornithine concentrations (57). In a second study, a 4 year old girl was given lysine supplementation (2.5-5 g/day) intermittently over a nine month period during which her protein intake was gradually decreased (11). Her plasma ornithine level dropped each time she was given lysine with the lowest values occurring when she was on the lowest protein diet (0.4-0.8 g/kg per day).…”

Section: Replacement Of Dejicient Productsmentioning

confidence: 99%

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Gyrate atrophy of the choroid and retina

1981

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Gyrate atrophy of the choroid and retina is caused by deficient activity of ornithine ketoacid aminotransferase, a pyridoxal phosphate dependent enzyme. Besides the typical eye findings, abnormalities have been found on muscle biopsy, electro-encephalography, electromyography and electrocardiography, establishing this as a generalized disorder. Ornithine is markedly elevated in plasma and other body fluids. Plasma lysine, glutamate, glutamine and creatine are reduced. The possible contributions of these biochemical disturbances to the pathogenesis of gyrate atrophy are discussed. The disease is one of the few examples of an inherited chorioretinal dystrophy whose underlying biochemical defect is known. It therefore offers a unique opportunity to develop and test rational approaches to therapy. These include lowering of the abnormally high ornithine by dietary restriction of its precursor arginine, facilitation of ornithine excretion by administration of alpha-aminoisobutyric acid, replacement of deficient products such as lysine or creatine, or increasing residual enzyme activity by high levels of cofactor (vitamin B6). The results of several studies employing such approaches to therapy are presented as well as preliminary indications of possible benefit in a few patients.

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“…Lysine and the nonmetabolizable amino acid a-aminoisobutyric acid (AIB) have both been reported to increase renal excretion of the dibasic amino acids (15)(16)(17) and might be useful in GA. Recently, Giordano et al (18) have reported that lysine supplementation diminished plasma ornithine significantly in a child with GA.…”

Section: Introductionmentioning

confidence: 99%