Δ1‐Pyrroline‐5‐carboxylate synthetase deficiency: An emergent multifaceted urea cycle‐related disorder

@article{MarcoMarn20201Pyrroline5carboxylateSD,
  title={$\Delta$1‐Pyrroline‐5‐carboxylate synthetase deficiency: An emergent multifaceted urea cycle‐related disorder},
  author={Clara Marco-Mar{\'i}n and Juan M Escamilla-Honrubia and Jos{\'e} Luis Ll{\'a}cer and Marco Seri and Emanuele Panza and Vicente Rubio},
  journal={Journal of Inherited Metabolic Disease},
  year={2020},
  volume={43},
  pages={657 - 670}
}
The bifunctional homooligomeric enzyme Δ1‐pyrroline‐5‐carboxylate synthetase (P5CS) and its encoding gene ALDH18A1 were associated with disease in 1998. Two siblings who presented paradoxical hyperammonemia (alleviated by protein), mental disability, short stature, cataracts, cutis laxa, and joint laxity, were found to carry biallelic ALDH18A1 mutations. They showed biochemical indications of decreased ornithine/proline synthesis, agreeing with the role of P5CS in the biosynthesis of these… 
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9 Citations

9 Citations

Citation Type

Citation Type

SPG9A with the new occurrence of an ALDH18A1 mutation in a CMT1A family with PMP22 duplication: case report
TLDR
This is the first SPG9A family with a de novo mutation or the new occurrence of gonadal mosaicism of ALDH18A1, and further studies are required to clarify the relationship between the amino acid levels and clinical manifestations, which will reveal how P5CS deficiency influences disease phenotypes.
Interorgan amino acid interchange in propionic acidemia: the missing key to understanding its physiopathology.
TLDR
The amino acid profile detected during decompensation episodes suggests deficient anaplerosis from propionyl-CoA and its precursors, with implications in other metabolic pathways like synthesis of urea cycle amino acids and ammonia detoxification.
Structural basis of dynamic P5CS filaments
TLDR
Cryo-electron microscopy reveals that filamentation is crucial for the coordination between the GK and GPR domains, providing a structural basis for the catalytic function of P5CS filaments.
Structural basis of dynamic P5CS filaments
TLDR
A previously undescribed mechanism that filamentation is crucial for the coordination between GK and GPR domains is revealed, and insights into structural basis for catalysis function of P5CS filament are provided.
Endocrinological disorders in children with cutis-laxa syndromes
TLDR
An overview of the endocrinological disturbances reported in association with cutis laxa syndromes is provided, with short stature, osteoporosis and fractures being the most frequent.
Eye involvement in inherited metabolic disorders
  • J. Davison
  • Medicine
    Therapeutic advances in ophthalmology
  • 2020
TLDR
awareness of inherited metabolic disorders is important to facilitate early diagnosis and in some cases instigate early treatment if a patient presents with eye involvement suggestive of a metabolic disorder.
A neonate with ornithine aminotransferase deficiency; insights on the hyperammonemia-associated biochemical phenotype of gyrate atrophy
Disorders of Ammonia Detoxification
  • J. Häberle, V. Rubio
  • Medicine
    Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases
  • 2022
Tremor as an early sign of hereditary spastic paraplegia due to mutations in ALDH18A1

References

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TLDR
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TLDR
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TLDR
A paradoxical hyperammonemia with hypoprolinemia and hypoornithinemia associated to bilateral cataract, mental retardation, joint laxity and skin hyperelasticity is described and the first report of a P5C synthetase deficiency in human is reported.
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TLDR
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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.
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TLDR
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TLDR
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TLDR
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TLDR
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