Inherited hyperornithinemia is characterised by mitochondrial ornithine aminotransferase deficiency. Onset may occur in neonatal period with hyperammonemic coma; however, normal ammonemia levels are rapidly and definitely restored soon after. The main clinical manifestation of the disease is gyrate atrophy of the choroid and retina that begins during childhood with myopia and night blindness, followed by concentric shrinking of the visual field (tunnel vision) and a peculiar aspect of retinopathy on the funduscopy. The electroretinogram soon goes flat. Patients often develop subcapsular posterior cataract between the ages of 10 and 20 and become virtually blind between the ages of 40 and 50. Most have normal intelligence, although some may be moderately retarded and exhibit proximal muscular disorders. It is transmitted as an autosomal recessive trait. Mitochondrial ornithine aminotransferase is involved in the transamination of ornithine and alpha ketoglutarate into delta-I-pyroline-5-carboxylate and has vitamin B6 for a cofactor. Two genetic forms have been described: a pyridoxine responsive form and a pyridoxine unresponsive form. Diagnosis is made by demonstrating major plasmatic and urinary hyperornithinemia on the chromatography of aminoacids, and confirmed by measuring enzymatic activity in lymphocytes or cultured fibroblasts. Patients are all tested for pyridoxine sensitivity during 2 weeks by receiving 500 mg to 1g of pyridoxine daily. As a result, ornithine-sensitive patients demonstrate normal plasmatic and urinary ornithinemia and should receive lifelong ornithine supplements. Ornithine-resistant patients should follow a diet with limited protein intake and may be supplemented with proline, although its efficiency is still controversed.
Last update: March 2004