Arginase Deficiency With New Phenotype and a Novel Mutation: Contemporary Summary

Tsang, Jane Pui Ki; Poon, Wai Lun; Luk, Ho Ming; Fung, Cheuk Wing; Ching, Chor Kwan; Mak, Chloe Miu; Lam, Ching Wan; Siu, Tak Shing; Tam, Sidney; Wong, Virginia

doi:10.1016/j.pediatrneurol.2012.06.012

Cited by 32 publications

(37 citation statements)

References 29 publications

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“…Besides the neurologic involvement, extraneurological symptoms are also present and the liver is the main affected organ. Hepatic involvement in argininemia can vary from mild hepatocellular injury with transient elevations of liver transaminases to coagulation abnormalities and hepatic failure as in other UCD [7-9, 12]. …”

Section: Discussionmentioning

confidence: 99%

“…Classic clinical manifestations of the disease are spastic paraparesis, mental retardation, failure to thrive, and episodic hyperammonemia, mostly starting in early childhood [2, 6]. Uncommon presentations of ARG1D with neonatal cholestasis or cirrhosis have been reported [7, 8, 9]. Transient elevations of liver transaminases and coagulopathy have been reported during episodes of hyperammonemia, but a permanent coagulopathy has never been reported [1, 2, 6].…”

Section: Introductionmentioning

confidence: 99%

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Coagulation Disturbances in Patients with Argininemia

et al. 2018

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Background: Argininemia is an autosomal recessive urea cycle disorder (UCD). Unlike other UCD, hyperammonemia is rarely seen. Patients usually present in childhood with neurological symptoms. Uncommon presentations like neonatal cholestasis or cirrhosis have been reported. Although transient elevations of liver transaminases and coagulopathy have been reported during hyperammonemia episodes, a permanent coagulopathy has never been reported. Methods: In this retrospective study, coagulation disturbances are examined in 6 argininemia patients. All of the patients were routinely followed up for hepatic involvement due to argininemia. Laboratory results, including liver transaminases, albumin, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and clotting factor levels, were assessed in all of the patients. Results: All of the patients had a prolonged PT and an increased INR, while none of the patients had a prolonged aPTT. Five patients had slightly elevated liver transaminases. A liver biopsy was performed in 1 patient but neither cirrhosis nor cholestasis was documented. Five of the 6 patients had low factor VII and factor IX levels, while other clotting factors were normal. Conclusions: Argininemia patients should be investigated for coagulation disorders even if there is no apparent liver dysfunction or major bleeding symptoms.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Coagulation Disturbances in Patients with Argininemia

et al. 2018

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“…Mild hepatic dysfunction with transient elevation of liver transaminases and coagulation abnormalities during catabolic episodes has been observed in a few patients with an otherwise typical neurological picture, and cases of persistent coagulopathy have been reported ( Scaglia and Lee 2006;Crombez and Cederbaum 2005;Brusilow 2001;Carvalho et al 2012b). Furthermore, a patient with liver cirrhosis and hepatocellular carcinoma without any other risk factors has been reported (Tsang et al 2012). Variable degrees of hepatic cirrhosis also occur in other UCDs (LaBrecque et al 1979;Mori et al 2002), and increased levels of l-arginine have been observed in patients with liver cirrhosis with progressive loss of renal function (Kayali et al 2009).…”

Section: Clinical Characteristicsmentioning

confidence: 99%

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature

et al. 2015

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Hyperargininemia is caused by deficiency of arginase 1, which catalyzes the hydrolysis of L-arginine to urea as the final enzyme in the urea cycle. In contrast to other urea cycle defects, arginase 1 deficiency usually does not cause catastrophic neonatal hyperammonemia but rather presents with progressive neurological symptoms including seizures and spastic paraplegia in the first years of life and hepatic pathology, such as neonatal cholestasis, acute liver failure, or liver fibrosis. Some patients have developed hepatocellular carcinoma. A usually mild or moderate hyperammonemia may occur at any age. The pathogenesis of arginase I deficiency is yet not fully understood. However, the accumulation of L-arginine and the resulting abnormalities in the metabolism of guanidine compounds and nitric oxide have been proposed to play a major pathophysiological role. This article provides an update on the first patients ever described, gives an overview of the distinct clinical characteristics, biochemical as well as genetical background and discusses treatment options.

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“…It is well known that Arg-I is mainly expressed in hepatocytes and is an essential enzyme involved in hepatic urea cycle for detoxification of ammonia (Crombez and Cederbaum, 2005; Tsang et al, 2012). In contrast, Arg-II is highly expressed in kidney (Yang and Ming, 2014).…”

Section: Introductionmentioning

confidence: 99%

Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity

et al. 2016

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Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II−/−) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II−/− mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II−/− mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II−/− mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

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Arginase Deficiency With New Phenotype and a Novel Mutation: Contemporary Summary

Cited by 32 publications

References 29 publications

Coagulation Disturbances in Patients with Argininemia

Coagulation Disturbances in Patients with Argininemia

Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature

Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity

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