Δ1-pyrroline-5-carboxylate synthase deficiency: neurodegeneration, cataracts and connective tissue manifestations combined with hyperammonaemia and reduced ornithine, citrulline, arginine and proline

@article{Baumgartner20051pyrroline5carboxylateSD,
  title={$\Delta$1-pyrroline-5-carboxylate synthase deficiency: neurodegeneration, cataracts and connective tissue manifestations combined with hyperammonaemia and reduced ornithine, citrulline, arginine and proline},
  author={Matthias R. Baumgartner and Daniel Rabier and Marie-C{\'e}cile Nassogne and Jean Louis Dufier and Jean Paul Padovani and Pierre P Kamoun and David Valle and Jean Marie Saudubray},
  journal={European Journal of Pediatrics},
  year={2005},
  volume={164},
  pages={31-36}
}
AbstractΔ1-pyrroline-5-carboxylate synthase (P5CS) catalyses the reduction of glutamate to Δ1-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine. Recently, we reported a newly recognised inborn error due to deficiency of P5CS in two sibs, one presenting at birth with hypotonia, dysmorphic signs, pes planus and clonic seizures. Both developed progressive neurodegeneration and peripheral neuropathy, joint laxity, skin hyperelasticity and bilateral… 
Understanding pyrroline-5-carboxylate synthetase deficiency: clinical, molecular, functional, and expression studies, structure-based analysis, and novel therapy with arginine
TLDR
Morphological and functional studies of fibroblast mitochondria show that P5CS deficiency is not associated with the mitochondrial alterations observed in Δ1-pyrroline-5-carboxylate reductase deficiency (another proline biosynthesis defect presenting cutis laxa and neurological alterations).
Defect in proline synthesis: pyrroline-5-carboxylate reductase 1 deficiency leads to a complex clinical phenotype with collagen and elastin abnormalities
TLDR
Additional six patients from four Iranian families with clinical manifestations of a wrinkly skin disorder are described, adding information on the natural course of PYCR1 deficiency and sheds light on the pathophysiology of this disorder.
Δ1‐Pyrroline‐5‐carboxylate synthetase deficiency: An emergent multifaceted urea cycle‐related disorder
TLDR
It is concluded that two neurocutaneous syndromes (recessive and dominant cutis laxa 3, abbreviated ARCL3A and ADCL3, respectively) and two SPG9 syndrome are caused by essentially different spectra of ALDH18A1 mutations, which represent a continuum of increasing severity.
Disorders of Ornithine Metabolism
TLDR
In the hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome there is a wide spectrum of clinical manifestations, most of which are related to the toxicity of hyper ammonemia.
Further expansion of the phenotypic spectrum associated with mutations in ALDH18A1, encoding Δ1‐pyrroline‐5‐carboxylate synthase (P5CS)
TLDR
The findings presented here emphasize the pleiotropic presentation of this group of conditions and suggest that multiple components of the extracellular matrix are perturbed in these disorders.
A missense mutation in ALDH18A1, encoding Δ1-pyrroline-5-carboxylate synthase (P5CS), causes an autosomal recessive neurocutaneous syndrome
TLDR
In an in vivo assay of flux through this metabolic pathway using dermal fibroblasts obtained from an affected individual, proline and ornithine biosynthetic activity of P5 CS was not affected by the H784Y substitution, suggesting that P5CS may possess additional uncharacterised functions that affect connective tissue and central nervous system function.
Compound heterozygous mutations in two different domains of ALDH18A1 do not affect the amino acid levels in a patient with hereditary spastic paraplegia
TLDR
This young man has spastic paraplegia with onset in childhood and temporal lobe epilepsy, but normal levels of proline, ornithine and arginine, which is the first case with compound heterozygous mutations affecting both P5CS domains, where levels of plasma amino acids have been reported.
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TLDR
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