ArticleJournal of inherited metabolic disease2012
Understanding pyrroline-5-carboxylate synthetase deficiency: clinical, molecular, functional, and expression studies, structure-based analysis, and novel therapy with arginine.
Article in Journal of inherited metabolic disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 59 citations in OpenAlex.
- Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment.Journal of human genetics · 2018Trial
- Transhepatic Gradients Reveal Selective Hepatic Processing Defects With Systemic Consequences in Cirrhosis.Comprehensive physiology · 2026Article
- Novel Compound-Heterozygous Variants in PYCR1 Expand the Variant Spectrum of Autosomal Recessive Cutis Laxa.Genes · 2026Article
- [Decreased plasma citrulline is a biochemical marker in newborn screening forZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Review
- Inborn Errors of Amino Acid Metabolism Revisited: Clinical Implications and Insights into Current Therapies.Journal of clinical medicine · 2025Review
- Successful pre-implantation genetic testing for autosomal recessive cutis laxa: clinical utility of a multidisciplinary team approach.Journal of assisted reproduction and genetics · 2025Article
- The aldehyde dehydrogenase superfamilies: correlations and deviations in structure and function.Applied microbiology and biotechnology · 2025Review
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- Single amino acid exchanges affect the substrate preference of an acetaldehyde dehydrogenase.Applied microbiology and biotechnology · 2025Article
- Quo vadis ureagenesis disorders? A journey from 90 years ago into the future.Journal of inherited metabolic disease · 2024Review
- Confirming the enzymatic activity and neurodevelopmental trajectory of PYCR1 mutation in one child with autosomal-recessive cutis laxa type 2.Molecular genetics and genomics : MGG · 2024Article
- [Expert consensus on the diagnosis and treatment of neonatal hyperammonemia].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Article
- Creatine Deficiency Disorders: Phenotypes, Genotypes, Diagnosis, and Treatment Outcomes.Turkish archives of pediatrics · 2023Article
- Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment.Neurogenetics · 2022Review
- Interorgan amino acid interchange in propionic acidemia: the missing key to understanding its physiopathology.Amino acids · 2022Observational
- Arterial dissections: Common features and new perspectives.Frontiers in cardiovascular medicine · 2022Review
- Clinical and Molecular Delineation of Cutis Laxa Syndromes: Paradigms for Homeostasis.Advances in experimental medicine and biology · 2021Review
- Urine creatine metabolite panel as a screening test in neurodevelopmental disorders.Orphanet journal of rare diseases · 2020Article
- Inborn errors of enzymes in glutamate metabolism.Journal of inherited metabolic disease · 2020Review
- Corticospinal tract damage in HHH syndrome: a metabolic cause of hereditary spastic paraplegia.Orphanet journal of rare diseases · 2019Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Δ(1)-Pyrroline-5-carboxylate synthetase (P5CS) catalyzes the first two steps of ornithine/proline biosynthesis. P5CS deficiency has been reported in three families, with patients presenting with cutis/joint laxity, cataracts, and neurodevelopmental delay. Only one family exhibited metabolic changes consistent with P5CS deficiency (low proline/ornithine/citrulline/arginine; fasting hyperammonemia). Here we report a new P5CS-deficient patient presenting the complete clinical/metabolic phenotype and carrying p.G93R and p.T299I substitutions in the γ-glutamyl kinase (γGK) component of P5CS. The effects of these substitutions are (1) tested in mutagenesis/functional studies with E.coli γGK, (2) rationalized by structural modelling, and (3) reflected in decreased P5CS protein in patient fibroblasts (shown by immunofluorescence). Using optical/electron microscopy on skin biopsy, we show collagen/elastin fiber alterations that may contribute to connective tissue laxity and are compatible with our angio-MRI finding of kinky brain vessels in the patient. MR spectroscopy revealed decreased brain creatine, which normalized after sustained arginine supplementation, with improvement of neurodevelopmental and metabolic parameters, suggesting a pathogenic role of brain creatine decrease and the value of arginine therapy. Morphological and functional studies of fibroblast mitochondria show that P5CS deficiency is not associated with the mitochondrial alterations observed in Δ(1)-pyrroline-5-carboxylate reductase deficiency (another proline biosynthesis defect presenting cutis laxa and neurological alterations).
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