Page last updated: 2024-10-21

urea and Argininosuccinate Synthase Deficiency Disease

urea has been researched along with Argininosuccinate Synthase Deficiency Disease in 22 studies

pseudourea: clinical use; structure
isourea : A carboximidic acid that is the imidic acid tautomer of urea, H2NC(=NH)OH, and its hydrocarbyl derivatives.

Research Excerpts

ExcerptRelevanceReference
"Citrullinemia type 1 (CTLN1) is a urea cycle disorder (UCD) caused by mutations of the ASS1 gene, which is responsible for production of the enzyme argininosuccinate synthetase (ASS), and classically presented as life-threatening hyperammonemia in newborns."7.85Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs. ( Kotaka, M; Nishikubo, T; Nomoto, K; Okamoto, S; Okita, K; Osafune, K; Soga, T; Takubo, N; Toyoda, T; Uemoto, S; Yasuchika, K; Yasuda, K; Yoshitoshi-Uebayashi, EY, 2017)
"We report the results of a 25-year, open-label, uncontrolled study of sodium phenylacetate and sodium benzoate therapy (Ammonul, Ucyclyd Pharma) in 299 patients with urea-cycle disorders in whom there were 1181 episodes of acute hyperammonemia."5.12Survival after treatment with phenylacetate and benzoate for urea-cycle disorders. ( Berry, GT; Berry, SA; Brusilow, SW; Enns, GM; Hamosh, A; Rhead, WJ, 2007)
"Citrullinemia type I (CTLN1) is a rare autosomal recessive disorder caused by mutations in the gene encoding argininosuccinate synthetase 1 (ASS1) that catalyzes the third step of the urea cycle."4.12Gene Therapy in Combination with Nitrogen Scavenger Pretreatment Corrects Biochemical and Behavioral Abnormalities of Infant Citrullinemia Type 1 Mice. ( Aldabe, R; Bazo, A; Bénichou, B; Combal, JP; Gonzalez-Aseguinolaza, G; Häberle, J; Lantero, A; Mauleón, I; Neri, L; Poms, M; Ricobaraza, A, 2022)
"The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive."3.85Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis. ( Garavelli, L; Ivanovski, A; Ivanovski, I; Ivanovski, P; Ješić, M, 2017)
"Citrullinemia type 1 (CTLN1) is a urea cycle disorder (UCD) caused by mutations of the ASS1 gene, which is responsible for production of the enzyme argininosuccinate synthetase (ASS), and classically presented as life-threatening hyperammonemia in newborns."3.85Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs. ( Kotaka, M; Nishikubo, T; Nomoto, K; Okamoto, S; Okita, K; Osafune, K; Soga, T; Takubo, N; Toyoda, T; Uemoto, S; Yasuchika, K; Yasuda, K; Yoshitoshi-Uebayashi, EY, 2017)
"Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) shows diverse metabolic abnormalities such as urea cycle dysfunction together with citrullinemia, galactosemia, and suppressed gluconeogenesis."3.75Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period. ( Hirano, K; Kobayashi, K; Miida, T; Momoi, T; Nagasaka, H; Ohura, T; Okano, Y; Saheki, T; Shigematsu, Y; Takayanagi, M; Tsukahara, H; Yorifuji, J; Yorifuji, T, 2009)
"One patient with OTC deficiency has had a liver transplant."1.35Hereditary urea cycle diseases in Finland. ( Keskinen, P; Salo, M; Siitonen, A, 2008)
"Urea cycle defect is an inborn error of ammonium metabolism caused by a deficient activity of the enzymes involved in urea synthesis."1.31Localized proton MR spectroscopy in infants with urea cycle defect. ( Choi, CG; Yoo, HW, 2001)

Research

Studies (22)

TimeframeStudies, this research(%)All Research%
pre-19901 (4.55)18.7374
1990's1 (4.55)18.2507
2000's12 (54.55)29.6817
2010's5 (22.73)24.3611
2020's3 (13.64)2.80

Authors

AuthorsStudies
Siri, B1
Olivieri, G1
Angeloni, A1
Cairoli, S1
Carducci, C1
Cotugno, G1
Di Michele, S1
Giovanniello, T1
La Marca, G1
Lepri, FR1
Novelli, A1
Rossi, C1
Semeraro, M1
Dionisi-Vici, C2
Bazo, A2
Lantero, A2
Mauleón, I2
Neri, L2
Poms, M2
Häberle, J3
Ricobaraza, A2
Bénichou, B2
Combal, JP2
Gonzalez-Aseguinolaza, G2
Aldabe, R2
Yau, WW1
Chen, GB1
Zhou, J1
Francisco, JC1
Thimmukonda, NK1
Li, S1
Singh, BK1
Yen, PM1
Herrera Sanchez, MB1
Previdi, S1
Bruno, S1
Fonsato, V1
Deregibus, MC1
Kholia, S1
Petrillo, S1
Tolosano, E1
Critelli, R1
Spada, M1
Romagnoli, R1
Salizzoni, M1
Tetta, C1
Camussi, G1
Ivanovski, I1
Ješić, M1
Ivanovski, A1
Garavelli, L1
Ivanovski, P1
Saheki, T5
Moriyama, M4
Kuroda, E1
Funahashi, A1
Yasuda, I1
Setogawa, Y1
Gao, Q1
Ushikai, M2
Furuie, S1
Yamamura, KI1
Takano, K1
Nakamura, Y2
Eto, K1
Kadowaki, T1
Sinasac, DS3
Furukawa, T1
Horiuchi, M4
Tai, YH1
Posset, R1
Garcia-Cazorla, A1
Valayannopoulos, V1
Teles, EL1
Brassier, A1
Burlina, AB1
Burgard, P1
Cortès-Saladelafont, E1
Dobbelaere, D1
Couce, ML1
Sykut-Cegielska, J1
Lund, AM1
Chakrapani, A1
Schiff, M1
Walter, JH1
Zeman, J1
Vara, R1
Kölker, S1
Yoshitoshi-Uebayashi, EY1
Toyoda, T1
Yasuda, K1
Kotaka, M1
Nomoto, K1
Okita, K1
Yasuchika, K1
Okamoto, S1
Takubo, N1
Nishikubo, T1
Soga, T1
Uemoto, S1
Osafune, K1
Tuchman, M1
Lee, B3
Lichter-Konecki, U1
Summar, ML1
Yudkoff, M1
Cederbaum, SD1
Kerr, DS1
Diaz, GA1
Seashore, MR1
Lee, HS1
McCarter, RJ1
Krischer, JP1
Batshaw, ML1
Keskinen, P1
Siitonen, A1
Salo, M1
Nagasaka, H1
Okano, Y1
Tsukahara, H1
Shigematsu, Y1
Momoi, T1
Yorifuji, J1
Miida, T1
Ohura, T1
Kobayashi, K4
Hirano, K1
Takayanagi, M1
Yorifuji, T1
MCMURRAY, WC1
MOHYUDDIN, F1
RATHBUN, JC1
Jalil, MA2
Begum, L2
Li, MX3
Iijima, M3
Robinson, BH1
Tsui, LC2
Lu, YB1
Tabata, A1
Hsiao, KJ1
Yang, Y1
Scaglia, F1
Carter, S1
O'Brien, WE1
Mandel, H1
Levy, N1
Izkovitch, S1
Korman, SH1
Singh, RH1
Rhead, WJ2
Smith, W1
Sniderman King, L1
Summar, M1
Kannan, Y1
Tanaka, M1
Enns, GM1
Berry, SA1
Berry, GT1
Brusilow, SW1
Hamosh, A1
Saudubray, JM1
Touati, G1
Delonlay, P1
Jouvet, P1
Narcy, C1
Laurent, J1
Rabier, D1
Kamoun, P1
Jan, D1
Revillon, Y1
Matsumura, R1
Choi, CG1
Yoo, HW1

Clinical Trials (2)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Longitudinal Study of Urea Cycle Disorders[NCT00237315]1,009 participants (Anticipated)Observational2006-02-28Recruiting
A Phase 2, Open-Label, Switch-Over, Dose-Escalation Study of the Safety and Tolerability of HPN-100 Compared to Buphenyl® (Sodium Phenylbutyrate) in Patients With Urea Cycle Disorders[NCT00551200]Phase 214 participants (Actual)Interventional2007-10-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Number of Subjects Experienced Adverse Events

(NCT00551200)
Timeframe: during the period on 100% Buphenyl (up to 4 weeks) or HPN-100 (up to 10 weeks)

Interventionparticipants (Number)
Buphenyl7
HPN-1005

Number of Subjects Experienced Serious Adverse Events

(NCT00551200)
Timeframe: during the period subjects on 100% Buphenyl (up to 4 weeks) or HPN-100 (up to 10 weeks)

Interventionparticipants (Number)
Buphenyl1
HPN-1000

Drug Preference for HPN-100 or Buphenyl® (as Assessed by Global Preference Question)

(NCT00551200)
Timeframe: End of Study

Interventionparticipants (Number)
prefer Buphenylprefer HPN-100
Buphenyl to HPN-10019

Pharmacokinetics (Plasma and Urine PK Parameters of Study Drugs and Their Metabolites)

measured AUC0-24 (Area under the curve from time 0 (pre-dose) to 24 hours) for each metabolite in plasma. Data were collected at 30 minutes and 1, 2, 4, 5, 6, 8, 10, 12, and 24 hours post-first dose. (NCT00551200)
Timeframe: At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone)

,
Interventionμg*h/mL (Mean)
AUC0-24 PBA (phenylbutyrate) in plasmaAUC0-24 PAA (phenylacetate) in plasmaAUC0-24 PAGN (phenylacetylglutamine) in plasma
HPN-100 Steady State5405751098
NaPBA Steady State7405961133

Venous Ammonia Levels at the Peak and Mean TNUAC Time-normalized Area Under the Curve)

Data were collected at pre-first dose and at 30 minutes and 1, 2, 4, 5, 6, 8, 10, 12, and 24 hours post first dose. (NCT00551200)
Timeframe: At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone), and at steady state (1 week) after each dose escalation

,
Interventionμmol/L (Mean)
in peakin TNAUC (time-normalized area under the curve)
HPN-100 Steady State56.326.5
NaPBA Steady State79.138.4

Reviews

3 reviews available for urea and Argininosuccinate Synthase Deficiency Disease

ArticleYear
Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle.
    Molecular genetics and metabolism, 2004, Volume: 81 Suppl 1

    Topics: Adult; Calcium-Binding Proteins; Citrullinemia; Female; Gene Frequency; Hepatitis; Humans; Infant, N

2004
Nutritional management of urea cycle disorders.
    Critical care clinics, 2005, Volume: 21, Issue:4 Suppl

    Topics: Acute Disease; Adolescent; Adult; Amino Acid Metabolism, Inborn Errors; Child; Child, Preschool; Chr

2005
[Disorders of the urea cycle].
    Ryoikibetsu shokogun shirizu, 2000, Issue:29 Pt 4

    Topics: Amino Acid Metabolism, Inborn Errors; Ammonia; Arginine; Argininosuccinic Acid; Citrullinemia; Human

2000

Trials

1 trial available for urea and Argininosuccinate Synthase Deficiency Disease

ArticleYear
Survival after treatment with phenylacetate and benzoate for urea-cycle disorders.
    The New England journal of medicine, 2007, May-31, Volume: 356, Issue:22

    Topics: Adolescent; Adult; Age Factors; Age of Onset; Amino Acid Metabolism, Inborn Errors; Ammonia; Carbamo

2007

Other Studies

18 other studies available for urea and Argininosuccinate Synthase Deficiency Disease

ArticleYear
The diagnostic challenge of mild citrulline elevation at newborn screening.
    Molecular genetics and metabolism, 2022, Volume: 135, Issue:4

    Topics: Citrulline; Citrullinemia; Humans; Infant, Newborn; Neonatal Screening; Urea; Urea Cycle Disorders,

2022
Gene Therapy in Combination with Nitrogen Scavenger Pretreatment Corrects Biochemical and Behavioral Abnormalities of Infant Citrullinemia Type 1 Mice.
    International journal of molecular sciences, 2022, Nov-29, Volume: 23, Issue:23

    Topics: Ammonia; Animals; Argininosuccinate Synthase; Citrullinemia; Genetic Therapy; Mice; Nitrogen; Urea

2022
Gene Therapy in Combination with Nitrogen Scavenger Pretreatment Corrects Biochemical and Behavioral Abnormalities of Infant Citrullinemia Type 1 Mice.
    International journal of molecular sciences, 2022, Nov-29, Volume: 23, Issue:23

    Topics: Ammonia; Animals; Argininosuccinate Synthase; Citrullinemia; Genetic Therapy; Mice; Nitrogen; Urea

2022
Gene Therapy in Combination with Nitrogen Scavenger Pretreatment Corrects Biochemical and Behavioral Abnormalities of Infant Citrullinemia Type 1 Mice.
    International journal of molecular sciences, 2022, Nov-29, Volume: 23, Issue:23

    Topics: Ammonia; Animals; Argininosuccinate Synthase; Citrullinemia; Genetic Therapy; Mice; Nitrogen; Urea

2022
Gene Therapy in Combination with Nitrogen Scavenger Pretreatment Corrects Biochemical and Behavioral Abnormalities of Infant Citrullinemia Type 1 Mice.
    International journal of molecular sciences, 2022, Nov-29, Volume: 23, Issue:23

    Topics: Ammonia; Animals; Argininosuccinate Synthase; Citrullinemia; Genetic Therapy; Mice; Nitrogen; Urea

2022
Nicotinamide riboside rescues dysregulated glycolysis and fatty acid β-oxidation in a human hepatic cell model of citrin deficiency.
    Human molecular genetics, 2023, 05-18, Volume: 32, Issue:11

    Topics: Aspartic Acid; Citrullinemia; Fatty Acids; Glycolysis; Hepatocytes; Humans; Hyperammonemia; Malates;

2023
Extracellular vesicles from human liver stem cells restore argininosuccinate synthase deficiency.
    Stem cell research & therapy, 2017, 07-27, Volume: 8, Issue:1

    Topics: Argininosuccinate Synthase; Citrullinemia; Extracellular Vesicles; Hepatocytes; Humans; Liver; Stem

2017
Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis.
    World journal of gastroenterology, 2017, Nov-28, Volume: 23, Issue:44

    Topics: Ammonia; Central Nervous System; Citrullinemia; Enterobacter; Fatal Outcome; Hepatocytes; Humans; Hy

2017
Pivotal role of inter-organ aspartate metabolism for treatment of mitochondrial aspartate-glutamate carrier 2 (citrin) deficiency, based on the mouse model.
    Scientific reports, 2019, 03-12, Volume: 9, Issue:1

    Topics: Amino Acids; Ammonia; Ammonium Chloride; Animals; Aspartic Acid; Citrulline; Citrullinemia; Disease

2019
Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders.
    Journal of inherited metabolic disease, 2016, Volume: 39, Issue:5

    Topics: Adolescent; Amino Acid Metabolism, Inborn Errors; Ammonium Compounds; Argininosuccinate Synthase; Ch

2016
Modelling urea-cycle disorder citrullinemia type 1 with disease-specific iPSCs.
    Biochemical and biophysical research communications, 2017, 05-06, Volume: 486, Issue:3

    Topics: Animals; Arginine; Argininosuccinate Synthase; Base Sequence; Cell Differentiation; Citric Acid Cycl

2017
Cross-sectional multicenter study of patients with urea cycle disorders in the United States.
    Molecular genetics and metabolism, 2008, Volume: 94, Issue:4

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Metabolism, Inborn Errors; Amino Acids; Child

2008
Hereditary urea cycle diseases in Finland.
    Acta paediatrica (Oslo, Norway : 1992), 2008, Volume: 97, Issue:10

    Topics: Adolescent; Adult; Amino Acid Metabolism, Inborn Errors; Argininosuccinic Aciduria; Carbamoyl-Phosph

2008
Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period.
    Molecular genetics and metabolism, 2009, Volume: 97, Issue:1

    Topics: Amino Acids; Apolipoproteins; Asian People; Biomarkers; Carbohydrates; Child; Child, Preschool; Citr

2009
CITRULLINURIA.
    Revista de neuro-psiquiatria, 1964, Volume: 27

    Topics: Amino Acid Metabolism, Inborn Errors; Citrulline; Citrullinemia; Clinical Enzyme Tests; Humans; Infa

1964
Slc25a13-knockout mice harbor metabolic deficits but fail to display hallmarks of adult-onset type II citrullinemia.
    Molecular and cellular biology, 2004, Volume: 24, Issue:2

    Topics: Amino Acids; Ammonia; Animals; Argininosuccinate Synthase; Aspartic Acid; Base Sequence; Citrullinem

2004
Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients.
    Molecular genetics and metabolism, 2004, Volume: 81 Suppl 1

    Topics: Adolescent; Adult; Amino Acid Metabolism, Inborn Errors; Amino Acids, Branched-Chain; Citrullinemia;

2004
Elevated plasma citrulline and arginine due to consumption of Citrullus vulgaris (watermelon).
    Journal of inherited metabolic disease, 2005, Volume: 28, Issue:4

    Topics: Adult; Arginine; Citrulline; Citrullinemia; Citrullus; Developmental Disabilities; Diet; Female; Hum

2005
Pyruvate ameliorates the defect in ureogenesis from ammonia in citrin-deficient mice.
    Journal of hepatology, 2006, Volume: 44, Issue:5

    Topics: Amino Acids; Ammonia; Animals; Anticoagulants; Aspartic Acid; Calcium-Binding Proteins; Citric Acid;

2006
Liver transplantation in urea cycle disorders.
    European journal of pediatrics, 1999, Volume: 158 Suppl 2

    Topics: Amino Acid Metabolism, Inborn Errors; Carbamoyl-Phosphate Synthase I Deficiency Disease; Child; Chil

1999
Localized proton MR spectroscopy in infants with urea cycle defect.
    AJNR. American journal of neuroradiology, 2001, Volume: 22, Issue:5

    Topics: Amino Acid Metabolism, Inborn Errors; Citrullinemia; Female; Humans; Infant; Infant, Newborn; Magnet

2001
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