Zusammenfassung
Hyperornithinaemia due to ornithine aminotransferase (OAT) deficiency results in gyrate atrophy of the choroid and retina (GA) and leads to progressive visual loss. Treatment includes an arginine-restricted diet and a trial of pyridoxine (vitamin B6) which, in some patients, can slow visual loss and chorioretinal degeneration. Rarely, neonates with OAT-deficiency present with hyperammonaemia and require treatment with arginine supplementation. In the hyperornithinaemia, hyperammonaemia, and homocitrullinuria (HHH) syndrome clinical manifestations are variable and may be related to intermittent episodes of hyperammonaemia. Progressive spastic paraparesis is often a late complication. Deficient transport of ornithine into the mitochondria impairs the urea cycle and results in episodic hyperammonaemia, hyperornithinaemia and increased urinary excretion of homocitrulline and orotic acid. Treatment includes protein restriction, citrulline or arginine supplementation and in some cases ammonia scavengers. P5C synthetase (P5CS) deficiency is a rare recessive neurocutaneous syndrome with cutis laxa, developmental delay, joint laxity and cataracts, but mutations affecting specific residues may also cause autosomal dominant cutis laxa as well as adult onset autosomal dominant spastic paraplegia. The metabolic phenotype includes mild hyperammonaemia, hypoornithinaemia, hypocitrullinaemia, hypoargininaemia and hypoprolinaemia. Deficiency of P5C reductase (P5CR) associated to mutations in PYCR1 causes autosomal recessive cutis laxa with progeroid features, while mutations in PYCR2, a paralog of PYCR1, cause microcephaly and hypomyelination. Both disorders show no apparent metabolic phenotype. The phenotypic consequences of Hyperprolinaemia type I are uncertain, while Hyperprolinaemia type II appears to be associated with a disposition to recurrent seizures. Prolidase deficiency causes skin lesions and recalcitrant ulceration in addition to other features, such as impaired psychomotor development and recurrent infections. The severity of clinical expression is highly variable.
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Baumgartner, M.R., Valle, D., Dionisi-Vici, C. (2016). Disorders of Ornithine and Proline Metabolism. In: Saudubray, JM., Baumgartner, M., Walter, J. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-49771-5_21
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