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Journal of Inherited Metabolic Disease

, Volume 36, Issue 4, pp 613–619 | Cite as

An update on serine deficiency disorders

  • S. N. van der Crabben
  • N. M. Verhoeven-Duif
  • E. H. Brilstra
  • L. Van Maldergem
  • T. Coskun
  • E. Rubio-Gozalbo
  • R. Berger
  • T. J. de KoningEmail author
Original Article

Abstract

Serine deficiency disorders are caused by a defect in one of the three synthesising enzymes of the L-serine biosynthesis pathway. Serine deficiency disorders give rise to a neurological phenotype with psychomotor retardation, microcephaly and seizures in newborns and children or progressive polyneuropathy in adult patients. There are three defects that cause serine deficiency of which 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, the defect affecting the first step in the pathway, has been reported most frequently. The other two disorders in L-serine biosynthesis phosphoserine aminotransferase (PSAT) deficiency and phosphoserine phosphatase (PSP) deficiency have been reported only in a limited number of patients. The biochemical hallmarks of all three disorders are low concentrations of serine in cerebrospinal fluid and plasma. Prompt recognition of affected patients is important, since serine deficiency disorders are treatable causes of neurometabolic disorders. The use of age-related reference values for serine in CSF and plasma can be of great help in establishing a correct diagnosis of serine deficiency, in particular in newborns and young children.

Keywords

Infantile Spasm West Syndrome Phosphoserine Phosphatase Phosphoserine Aminotransferase Congenital Microcephaly 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Conflict of interest

None

References

  1. De Klerk JB, Huijmans JGM, Catsman-Berrevoets CE, et al Disturbed biosyn- thesis o(1f serine: a second phenotype with axonal polyneuropathy and ichthyosis. Abstracts of the annual meeting of the Erfelijke Stofwisselingsziekten Nederland; October 13, 1996; Masstricht, the NetherlandsGoogle Scholar
  2. de Koning TJ (2012) Serine synthesis defects and epilepsy (chapter 18) In: Pearl P (ed) Inherited metabolic epilepsies. Demos Medical Publishing, New York.Google Scholar
  3. de Koning TJ, Duran M, Dorland L et al (1998) Beneficial effects of L-serine and glycine in the management of seizures in 3-phosphoglycerate dehydrogenase deficiency. Ann Neurol 44(2):261–265PubMedCrossRefGoogle Scholar
  4. de Koning TJ, Jaeken J, Pineda M, Van ML, Poll-The BT, van der Knaap MS (2000) Hypomyelination and reversible white matter attenuation in 3-phosphoglycerate dehydrogenase deficiency. Neuropediatrics 31(6):287–292PubMedCrossRefGoogle Scholar
  5. de Koning TJ, Duran M, Van ML et al (2002) Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. J Inherit Metab Dis 25(2):119–125PubMedCrossRefGoogle Scholar
  6. de Koning TJ, Klomp LW, van Oppen AC et al (2004) Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency. Lancet 364:2221–2222PubMedCrossRefGoogle Scholar
  7. Hart CE, Race V, Achouri Y et al (2007) Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway. Am J Hum Genet 80:931–937PubMedCrossRefGoogle Scholar
  8. Hausler MG, Jaeken J, Monch E, Ramaekers VT (2001) Phenotypic heterogeneity and adverse effects of serine treatment in 3-phosphoglycerate dehydrogenase deficiency: report on two siblings. Neuropediatrics 32(4):191–195PubMedCrossRefGoogle Scholar
  9. Jaeken J, Detheux M, Van Maldergem L, Frijns JP, Alliet P, Foulon M, Carchon H, Van Schaftingen E (1996a) 3-Phosphoglycerate dehydrogenase deficiency and 3-phosphoserine phosphatase deficiency: inborn errors of serine biosynthesis. J Inherit Metab Dis 19:223–226PubMedCrossRefGoogle Scholar
  10. Jaeken J, Detheux M, Van ML, Foulon M, Carchon H, Van SE (1996b) 3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis. Arch Dis Child 74(6):542–545PubMedCrossRefGoogle Scholar
  11. Jaeken J, Detheux M, Fryns JP et al (1997) Phosphoserine phosphatase deficiency in a patient with Williams syndrome. J Med Genet 34:594–596PubMedCrossRefGoogle Scholar
  12. Keularts IM, Leroy PL, Rubio-Gozalbo EM, Spaapen LJ, Weber B, Dorland B, de Koning TJ, Verhoeven-Duif NM (2010) Fatal cerebral edema associated with serine deficiency in CSF. J Inherit Metab Dis doi: 10.1007/s10545-010-9067-9
  13. Méneret A, Wiame E, Marelli C, Lenglet T, Van Schaftingen E, Sedel F (2012) A serine synthesis defect presenting with a charcot-marie-tooth-like polyneuropathy. Arch Neurol 69(7):908-11Google Scholar
  14. Moat SJ, Carling R, Nix B, Henderson M, Briddon A, Prunty H, Talbot R, Powell A, Wright K, Fuchs SA, de Koning TJ (2010) Multicentre age related reference intervals for cerebrospinal fluid serine: Implications for the diagnosis and follow-up of serine biosynthesis disorders. Mol Genet Metab 101:149–152PubMedCrossRefGoogle Scholar
  15. Pind S, Slominski E, Mauthe J et al (2002) V490M, a common mutation in 3-phosphoglycerate dehydrogenase deficiency, causes enzyme deficiency by decreasing the yield of mature enzyme. J Biol Chem 277(9):7136–7143PubMedCrossRefGoogle Scholar
  16. Pineda M, Vilaseca MA, Artuch R et al (2000) 3-phosphoglycerate dehydrogenase deficiency in a patient with West syndrome. Dev Med Child Neurol 42(9):629–633PubMedCrossRefGoogle Scholar
  17. Surtees R, Bowron A, Leonard J (1997) Cerebrospinal fluid and plasma total homocysteine and related metabolites in children with cystathionine beta-synthase deficiency: the effect of treatment. Pediatr Res 42:577–582PubMedCrossRefGoogle Scholar
  18. Tabatabaie L, de Koning TJ, Geboers AJ (2009) van dB, I, Berger R, Klomp LW. Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed throughout the protein and result in altered enzyme kinetics. Hum Mutat 30(5):749–756PubMedCrossRefGoogle Scholar
  19. Tabatabaie L, Klomp LWJ, Rubio-Gozalbo ME, Spaapen LJM, Haagen AAM, Dorland L, de Koning TJ (2011) Expanding the Clinical Spectrum of 3-Phosphoglycerate Dehydrogenase Deficiency. J Inherit Metab Dis 34(1):181–184PubMedCrossRefGoogle Scholar
  20. Veiga-da-Cunha M, Collet JF, Prieur B et al (2004) Mutations responsible for 3-phosphoserine phosphatase deficiency. Eur J Hum Genet 12:163–166PubMedCrossRefGoogle Scholar
  21. Visser WF, Verhoeven-Duif NM, Ophoff R, Bakker S, Klomp LW, Berger R, de Koning TJ (2011) A sensitive and simple ultra-high-performance-liquid chromatography-tandem mass spectrometry based method for the quantification of D-amino acids in body fluids. J Chromatogr A 1218:7130–7136PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • S. N. van der Crabben
    • 1
  • N. M. Verhoeven-Duif
    • 2
  • E. H. Brilstra
    • 1
  • L. Van Maldergem
    • 3
  • T. Coskun
    • 4
  • E. Rubio-Gozalbo
    • 5
  • R. Berger
    • 6
  • T. J. de Koning
    • 7
    Email author
  1. 1.Department of Medical GeneticsUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Department of Metabolic DiseasesUniversity Medical Center UtrechtUtrechtthe Netherlands
  3. 3.Centre de Génétique HumaineUniversité de Franche-ComtéBesançonFrance
  4. 4.Department of Metabolic DiseasesHacettepe University Faculty of MedicineAnkaraTurkey
  5. 5.Department of PediatricsMaastricht University Medical CentreMaastrichtThe Netherlands
  6. 6.Division of Analytical Biosciences, Netherlands Metabolomics Centre, LACDRLeiden UniversityLeidenThe Netherlands
  7. 7.Departments of Genetics and NeurologyUniversity of Groningen, HP CB 50, University Medical Center GroningenGroningenThe Netherlands

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