Research & Literature

Ornithine In Vivo Administration Disrupts Redox Homeostasis and Decreases Synaptic Na(+), K (+)-ATPase Activity in Cerebellum of Adolescent Rats: Implications for the Pathogenesis of Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) Syndrome.

Zanatta Â, Viegas CM, Hickmann FH, et al.

Cellular and molecular neurobiology 2015; (35(6)):797-806 doi:10.1007/s10571-015-0173-y.

Pathogenic potential of SLC25A15 mutations assessed by transport assays and complementation of Saccharomyces cerevisiae ORT1 null mutant.

Marobbio CM, Punzi G, Pierri CL, et al.

Molecular genetics and metabolism 2015; (115(1)):27-32.

The hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.

Martinelli D, Diodato D, Ponzi E, et al.

Orphanet journal of rare diseases 2015; (10()):29 doi:10.1186/s13023-015-0242-9.

[Diagnosis and treatment of urea cycle disorders in adult patients].

Maillot F, Blasco H, Lioger B, et al.

La Revue de medecine interne 2016; (37(10)):680-684 doi:10.1016/j.revmed.2016.02.011.

Ornithine and Homocitrulline Impair Mitochondrial Function, Decrease Antioxidant Defenses and Induce Cell Death in Menadione-Stressed Rat Cortical Astrocytes: Potential Mechanisms of Neurological Dysfunction in HHH Syndrome.

Zanatta Â, Rodrigues MD, Amaral AU, et al.

Neurochemical research 2016; (41(9)):2190-8 doi:10.1007/s11064-016-1933-x.

Improving long term outcomes in urea cycle disorders-report from the Urea Cycle Disorders Consortium.

Waisbren SE, Gropman AL, , Batshaw ML

Journal of inherited metabolic disease 2016; (39(4)):573-84 doi:10.1007/s10545-016-9942-0.

Efficacy and safety of i.v. sodium benzoate in urea cycle disorders: a multicentre retrospective study.

Husson MC, Schiff M, Fouilhoux A, et al.

Orphanet journal of rare diseases 2016; (11(1)):127 doi:10.1186/s13023-016-0513-0.

[Clinical diagnosis and treatment of three cases with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome].

Guan HZ, Ding Y, Li DX, et al.

Zhonghua er ke za zhi = Chinese journal of pediatrics 2017; (55(6)):428-433 doi:10.3760/cma.j.issn.0578-1310.2017.06.007.

The impact of ammonia levels and dialysis on outcome in 202 patients with neonatal onset urea cycle disorders.

Hediger N, Landolt MA, Diez-Fernandez C, et al.

Journal of inherited metabolic disease 2018; (41(4)):689-698 doi:10.1007/s10545-018-0157-4.

Hyperornithinemia, Hyperammonemia, and Homocitrullinuria Syndrome Causing Severe Neonatal Hyperammonemia.

Wild KT, Ganetzky RD, Yudkoff M, Ierardi-Curto L

JIMD reports 2019; (44()):103-107 doi:10.1007/8904_2018_132.

Late onset hyperornithinemia-hyperammonemia-homocitrullinuria syndrome - how web searching by the family solved unexplained unconsciousness: a case report.

Silfverberg T, Sahlander F, Enlund M, et al.

Journal of medical case reports 2018; (12(1)):274 doi:10.1186/s13256-018-1794-9.

Evaluation of dietary treatment and amino acid supplementation in organic acidurias and urea-cycle disorders: On the basis of information from a European multicenter registry.

Molema F, Gleich F, Burgard P, et al.

Journal of inherited metabolic disease 2019; (42(6)):1162-1175 doi:10.1002/jimd.12066.

Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment.

Molema F, Gleich F, Burgard P, et al.

Molecular genetics and metabolism 2019; (126(4)):397-405 doi:10.1016/j.ymgme.2019.02.003.

Hereditary Spastic Paraplegia Is a Common Phenotypic Finding in ARG1 Deficiency, P5CS Deficiency and HHH Syndrome: Three Inborn Errors of Metabolism Caused by Alteration of an Interconnected Pathway of Glutamate and Urea Cycle Metabolism.

Panza E, Martinelli D, Magini P, et al.

Frontiers in neurology 2019; (10()):131 doi:10.3389/fneur.2019.00131.

Chronic liver involvement in urea cycle disorders.

Ranucci G, Rigoldi M, Cotugno G, et al.

Journal of inherited metabolic disease 2019; (42(6)):1118-1127 doi:10.1002/jimd.12144.

Corticospinal tract damage in HHH syndrome: a metabolic cause of hereditary spastic paraplegia.

Olivieri G, Pro S, Diodato D, et al.

Orphanet journal of rare diseases 2019; (14(1)):208 doi:10.1186/s13023-019-1181-7.

Extracorporeal Ammonia Clearance for Hyperammonemia in Critically Ill Patients: A Scoping Review.

Naorungroj T, Yanase F, Eastwood GM, et al.

Blood purification 2021; (50(4-5)):453-461 doi:10.1159/000512100.

Successful liver transplantation in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome: Case report.

De Bruyne P, Verloo P, Van Hove JLK, et al.

Pediatric transplantation 2021; (25(6)):e13943 doi:10.1111/petr.13943.

Role of early management of hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome in pregnancy.

Billingham MJ, Rizk R

BMJ case reports 2021; (14(7)) doi:10.1136/bcr-2020-241424.

Reversible Leukoencephalopathy in a Man with Childhood-onset Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome.

Hoshino Y, Kodaira M, Matsuno A, et al.

Internal medicine (Tokyo, Japan) 2022; (61(4)):553-557 doi:10.2169/internalmedicine.7843-21.

Characteristics of continuous venovenous hemodiafiltration in the acute treatment of inherited metabolic disorders.

Eminoğlu FT, Öncül Ü, Kahveci F, et al.

Pediatric nephrology (Berlin, Germany) 2022; (37(6)):1387-1397 doi:10.1007/s00467-021-05329-9.

Multisite Retrospective Review of Outcomes in Renal Replacement Therapy for Neonates with Inborn Errors of Metabolism.

Ames EG, Powell C, Engen RM, et al.

The Journal of pediatrics 2022; (246()):116-122.e1 doi:10.1016/j.jpeds.2022.03.043.

Immune Alterations in a Patient With Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome: A Case Report.

Silvera-Ruiz SM, Gemperle C, Peano N, et al.

Frontiers in immunology 2022; (13()):861516 doi:10.3389/fimmu.2022.861516.

Clinical heterogeneity of hyperornithinemia-hyperammonemia-homocitrullinuria syndrome in thirteen palestinian patients and report of a novel variant in the SLC25A15 gene.

Dweikat I, Khalaf-Nazzal R

Frontiers in genetics 2022; (13()):1004598 doi:10.3389/fgene.2022.1004598.

Urea cycle disorders in critically Ill adults.

Long MT, Kruser JM, Quinonez SC

Current opinion in clinical nutrition and metabolic care 2024; (27(2)):184-191 doi:10.1097/MCO.0000000000000992.

Hyperornithinemia-hyperammonemia-homocitrullinuria: a rare neurometabolic disorder in two siblings.

Rizkallah D, Daher RT, Haddad L, Karam PE

Metabolic brain disease 2024; (39(5)):909-913 doi:10.1007/s11011-024-01366-z.

Postoperative hyperammonemic encephalopathy due to unexpected constipation in a patient with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome: a case report.

Tachibana H, Ohashi N, Okumura G, et al.

JA clinical reports 2024; (10(1)):42 doi:10.1186/s40981-024-00726-z.

A Novel Mutation of ORNT1 Detected in a Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome Child by Clinical Whole-Exome Sequencing.

Laochareonsuk W, Osatakul S, Intusoma U, et al.

Journal of pediatric genetics 2024; (13(3)):205-210 doi:10.1055/s-0041-1742247.

Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome in Vietnamese Patients.

Nguyen KN, Tran VK, Nguyen NL, et al.

Medicina (Kaunas, Lithuania) 2024; (60(11)) doi:10.3390/medicina60111877.

Urea cycle defects in adulthood: clinical presentation, diagnosis and treatment in genetically encoded hepatic metabolic disorders with a potential for encephalopathy.

Das AM

Metabolic brain disease 2025; (40(5)):192 doi:10.1007/s11011-025-01619-5.

Hyperammonemia in urea cycle disorders: A toxic metabolite for the brain.

Kido J, Nakamura K

Pediatrics international : official journal of the Japan Pediatric Society 2025; (67(1)):e70121 doi:10.1111/ped.70121.

Liver transplantation can prevent the progression of neurological damage in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome and maintain long-term metabolic stability - The largest single-center experience.

Ju H, Wang J, Wang X, et al.

Orphanet journal of rare diseases 2025; (20(1)):532 doi:10.1186/s13023-025-04077-5.

Rebound hyperammonemia triggered by interruption of renal replacement therapy in adolescent ornithine transcarbamylase deficiency.

Nakano Y, Otani S, Terazawa M, et al.

The journal of medical investigation : JMI 2025; (72(3.4)):443-446 doi:10.2152/jmi.72.443.

Severe Neurological Sequelae and Radiological Findings in a Lost-to-Follow-Up Case of Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome.

Mohamed AS, Gupta A, Zakzouk RS

Cureus 2025; (17(10)):e93690 doi:10.7759/cureus.93690.

Biochemical testing and pathology reveal rare cause of pediatric acute liver failure: Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.

Mosher TL, Czepiel KS, Neu MB, et al.

JPGN reports 2026; doi:10.1002/jpr3.70206.