N -carbamoylglutamate-responsive carbamoyl phosphate synthetase 1 (CPS1) deficiency: A patient with a novel CPS1 mutation and an experimental study on the mutation's effects

JIMD Reports
Sufin YapVicente Rubio

Abstract

N-carbamoyl-l-glutamate (NCG), the N-acetyl-l-glutamate analogue used to treat N-acetylglutamate synthase deficiency, has been proposed as potential therapy of carbamoyl phosphate synthetase 1 deficiency (CPS1D). Previous findings in five CPS1D patients suggest that NCG-responsiveness could be mutation-specific. We report on a patient with CPS1D, homozygous for the novel p.(Pro1211Arg) CPS1 mutation, who presented at 9 days of life with hyperammonemic coma which was successfully treated with emergency measures. He remained metabolically stable on merely oral NCG, arginine, and modest protein restriction. Ammonia scavengers were only added after poor dietary compliance following solid food intake at age 1 year. The patient received a liver transplantation at 3.9 years of age, having normal cognitive, motor, and quality of life scores despite repeated but successfully treated episodes of hyperammonemia. Studies using recombinantly produced mutant CPS1 confirmed the partial nature of the CPS1D triggered by the p.(Pro1211Arg) mutation. This mutation decreased the solubility and yield of CPS1 as expected for increased tendency to misfold, and reduced the thermal stability, maximum specific activity (Vmax; ~2-fold reduction), and app...Continue Reading

References

Jan 1, 1981·Enzyme·V Rubio, S Grisolia
Aug 6, 1981·Nature·V Rubio, S Grisolía
Aug 30, 2005·The Journal of Pediatrics·Nathalie GuffonChristine Vianey-Saban
Dec 3, 2005·Molecular Genetics and Metabolism·Ljubica CaldovicMendel Tuchman
Mar 27, 2007·Cellular Microbiology·Daniel E Voth, Robert A Heinzen
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Oct 13, 2011·Molecular Systems Biology·Fabian SieversDesmond G Higgins
May 31, 2012·Orphanet Journal of Rare Diseases·Johannes HäberleCarlo Dionisi-Vici
Apr 1, 2014·Nature Methods·Jana Marie SchwarzDominik Seelow
Aug 20, 2016·Orphanet Journal of Rare Diseases·Caroline UnsinnJohannes Häberle
Mar 11, 2017·Expert Opinion on Therapeutic Targets·Carmen Diez-Fernandez, Johannes Häberle
Jul 26, 2017·Journal of Clinical Pharmacy and Therapeutics·E KoseY Ozturk

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Citations

Oct 11, 2020·Orphanet Journal of Rare Diseases·Aileen Kenneson, Rani H Singh
Dec 16, 2020·Molecular Genetics and Metabolism·Matthew Nitzahn, Gerald S Lipshutz

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Methods Mentioned

BETA
electrophoresis

Software Mentioned

Clustal
PedsQL
GraphPad Prism
Multi Gauge
Pymol
PolyPhen
GraphPad

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