Amino acid synthesis deficiencies

T. J. de Koning*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

19 Citations (Scopus)
435 Downloads (Pure)

Abstract

In recent years the number of disorders known to affect amino acid synthesis has grown rapidly. Nor is it just the number of disorders that has increased: the associated clinical phenotypes have also expanded spectacularly, primarily due to the advances of next generation sequencing diagnostics. In contrast to the "classical" inborn errors of metabolism in catabolic pathways, in which elevated levels of metabolites are easily detected in body fluids, synthesis defects present with low values of metabolites or, confusingly, even completely normal levels of amino acids. This makes the biochemical diagnosis of this relatively new group of metabolic diseases challenging. Defects in the synthesis pathways of serine metabolism, glutamine, proline and, recently, asparagine have all been reported. Although these amino acid synthesis defects are in unrelated metabolic pathways, they do share many clinical features. In children the central nervous system is primarily affected, giving rise to (congenital) microcephaly, early onset seizures and varying degrees of mental disability. The brain abnormalities are accompanied by skin disorders such as cutis laxa in defects of proline synthesis, collodion-like skin and ichthyosis in serine deficiency, and necrolytic erythema in glutamine deficiency. Hypomyelination with accompanying loss of brain volume and gyration defects can be observed on brain MRI in all synthesis disorders. In adults with defects in serine or proline synthesis, spastic paraplegia and several forms of polyneuropathy with or without intellectual disability appear to be the major symptoms in these late-presenting forms of amino acid disorders. This review provides a comprehensive overview of the disorders in amino acid synthesis.

Original languageEnglish
Pages (from-to)609-620
Number of pages12
JournalJournal of Inherited Metabolic Disease
Volume40
Issue number4
DOIs
Publication statusPublished - Jul-2017
EventAnnual Symposium of the Society-for-the-Study-of-Inborn-Errors-of-Metabolism (SSIEM) - Rome, Italy
Duration: 6-Sep-20169-Sep-2016

Keywords

  • 3-PHOSPHOGLYCERATE DEHYDROGENASE-DEFICIENCY
  • ENCODING DELTA(1)-PYRROLINE-5-CARBOXYLATE SYNTHASE
  • ASPARAGINE SYNTHETASE DEFICIENCY
  • SERINE BIOSYNTHESIS PATHWAY
  • RECESSIVE CUTIS LAXA
  • NEU-LAXOVA SYNDROME
  • GLUTAMINE-SYNTHETASE
  • INTELLECTUAL DISABILITY
  • MUTATIONS CAUSE
  • INBORN-ERRORS

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