Abstract
Four disorders of proline metabolism are known: two in its catabolism (hyperprolinaemia type I, which is due to proline oxidase deficiency, and hyperprolinaemia type II, which is due to ∆-pyrroline 5-carboxylate dehydrogenase deficiency) and two in its synthesis (∆1-pyrroline 5-carboxylate synthase deficiency and ∆-pyrroline 5-carboxylate reductase deficiency). Hyperprolinaemia type I is generally considered a nondisease, while hyperprolinaemia type II appears to be associated with a disposition to recurrent seizures. The deficiency of the proline-synthesising enzyme, ∆-pyrroline 5-carboxylate synthase, which is also involved in ornithine synthesis, is described in ► Chapter 22.
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References
Scriver CR, Schafer IA, Efron ML (1961) New renal tubular amino acid transport system and a new hereditary disorder of amino acid metabolism. Nature 192:672
Aral B, Kamoun P (1997) The proline biosynthesis in living organisms. Amino Acids 13:189–217
Jacquet H, Raux G, Thibaut F et al. (2002) PRODH mutations and hyperprolinemia in a subset of schizophrenic patients. Hum Mol Genet 11:2243–2249
Bender HU, Almasham S, Steel G et al. (2005) Functional consequences of PRODH missense mutations. Am J Hum Genet 76:409–420
Jaeken J, Goemans N, Fryns J-P et al. (1996) Association of hyperprolinemia type I and heparin cofactor II deficiency with CATCH 22 syndrome: evidence for a contiguous gene syndrome locating the proline oxidase gene. J Inherit Metab Dis 19:275–277
Farrant RD, Walker V, Mills GA et al. (2000) Pyridoxal phosphate deactivation by pyrroline-5-carboxylic acid. Increased risk of vitamin B6 deficiency and seizures in hyperprolinemia type II. J Biol Chem 276:15107–15116
Clayton PT (2006) B6-Responsive disorders: a model of vitamin dependency. J Inherit Metab Dis 29:317–326
Geraghty MT, Vaughn D, Nicholson AJ et al. (1998) Mutations in the delta 1-pyrroline 5-carboxylate dehydrogenase gene cause type II hyperprolinemia. Hum Mol Genet 7:1411–1415
Guemsy DL, Jiang H, Evans SC et al. (2009) Mutation in pyrroline-5-carboxylate reductase 1 gene in families with cutis laxa type 2. Am J Med Genet 85:120–129
Reversade B, Escande-Beillard N, Dimopoulou A et al. (2009) Mutations in PYCR1 cause cutis laxa with progeroid features. Nat Genet 41:1016–1021
Jaeken J, Detheux M, Maldergem v L et al. (1996) 3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis. Arch Dis Child 74:542–545
Tabatabaie L, Klomp LW, Berger R, de Koning TJ (2010) l-Serine synthesis in the central nervous system: a review on serine deficiency disorders. Mol Genet Metab 99:256–262
Tabatabaie L, de Koning TJ, Geboers AJ et al. (2009) Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed throughout the protein and result in altered enzyme kinetics. Hum Mutat 30:749–756
Klomp LW, de Koning TJ, Malingre HE et al. (2000) Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency – a neurometabolic disorder associated with reduced l-serine biosynthesis. Am J Hum Genet 67:1389–1399
De Koning TJ, Klomp LW, van Oppen AC et al. (2004) Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency. Lancet 364:2221–2222
De Koning TJ, Jaeken J, Pineda M et al. (2000) Hypomyelination and reversible white matter attenuation in 3-phosphoglycerate dehydrogenase deficiency. Neuropediatrics 31:287–292
Hart CE, Race V, Achouri Y et al. (2007) Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway. Am J Hum Genet 80:931–937
Jaeken J, Detheux M, Fryns J-P et al. (1997) Phosphoserine phosphatase deficiency in a patient with Williams syndrome. J Med Genet 34:594–596
Veiga-da-Cunha M, Collet JF, Prieur B et al. (2004) Mutations responsible for 3-phosphoserine phosphatase deficiency. Eur J Hum Genet 12:163–166
De Klerk JB, Huijmans JGM, Catsman-Berrevoets CE et al. (1996) Disturbed biosynthesis of serine; a second phenotype with axonal polyneuropathy and ichthyosis. Abstracts of the annual meeting of the Erfelijke Stofwisselingsziekten Nederland, Maastricht, 13–15 Oct 1996
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Jaeken, J. (2012). Disorders of Proline and Serine Metabolism. In: Saudubray, JM., van den Berghe, G., Walter, J.H. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-15720-2_25
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DOI: https://doi.org/10.1007/978-3-642-15720-2_25
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