Effects of arginine treatment on nutrition, growth and urea cycle function in seven Japanese boys with late-onset ornithine transcarbamylase deficiency

Nagasaka, Hironori; Yorifuji, Tohru; Murayama, Kei; Kubota, Minoru; Kurokawa, Keiji; Murakami, Tomoko; Kanazawa, Masato; Takatani, Tomozumi; Ogawa, Atsushi; Ogawa, Emi; Yamamoto, Shozo; Adachi, Masanori; Kobayashi, Kunihiko; Takayanagi, Masaki

doi:10.1007/s00431-006-0143-y

Cited by 27 publications

(17 citation statements)

References 31 publications

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“…These intermediates become limiting particularly when they are massively excreted into the urine as in ASLD and to a lesser extent in ASSD. In these diseases, ASA and citrulline serve as vehicles for nitrogen removal via their excretion in the urine, and thus the provision of arginine reduces the frequency of hyperammonemic episodes . Fasting plasma arginine concentrations should be about 70 to 120 μmol/L .…”

Section: Long‐term Management Of Ucdsmentioning

confidence: 99%

Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision

Häberle

Burlina²,

Chakrapani

et al. 2019

J of Inher Metab Disea

335

478

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In 2012, we published guidelines summarizing and evaluating late 2011 evidence for diagnosis and therapy of urea cycle disorders (UCDs). With 1:35 000 estimated incidence, UCDs cause hyperammonemia of neonatal (~50%) or late onset that can lead to intellectual disability or death, even while effective therapies do exist. In the 7 years increased awareness among health professionals and patient families. However, underrecognition and delayed diagnosis of UCDs still appear widespread. It was therefore necessary to revise the original guidelines to ensure an up-to-date frame of reference for professionals and patients as well as for awareness campaigns. This was accomplished by keeping the original spirit of providing a trans-European consensus based on robust evidence (scored with GRADE methodology), involving professionals on UCDs from nine countries in preparing this consensus. We believe this revised guideline, which has been reviewed by several societies that are involved in the management of UCDs, will have a positive impact on the outcomes of patients by establishing common standards, and spreading and harmonizing good practices. It may also promote the identification of knowledge voids to be filled by future research.

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Section: Long‐term Management Of Ucdsmentioning

confidence: 99%

Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision

Häberle

Burlina²,

Chakrapani

et al. 2019

J of Inher Metab Disea

335

478

View full text Add to dashboard Cite

show abstract

“…Interestingly, the effect of Arg provision was greater for low-birth-weight piglets than for their normal-birth-weight littermates (Kim and Wu 2008), suggesting a lower rate of endogenous Arg synthesis in IUGR piglets. Similarly, oral administration of Arg (3 × 55–70 mg/kg body weight per day) for 3–18 months prevented ammonia toxicity and enhanced growth of infants with an inborn deficiency of Arg synthesis (Nagasaka et al 2006). …”

Section: Arginine and Neonatal Growthmentioning

confidence: 99%

Arginine metabolism and nutrition in growth, health and disease

et al. 2008

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L-Arginine (Arg) is synthesised from glutamine, glutamate, and proline via the intestinal-renal axis in humans and most other mammals (including pigs, sheep and rats). Arg degradation occurs via multiple pathways that are initiated by arginase, nitric-oxide synthase, Arg:glycine amidinotransferase, and Arg decarboxylase. These pathways produce nitric oxide, polyamines, proline, glutamate, creatine, and agmatine with each having enormous biological importance. Arg is also required for the detoxification of ammonia, which is an extremely toxic substance for the central nervous system. There is compelling evidence that Arg regulates interorgan metabolism of energy substrates and the function of multiple organs. The results of both experimental and clinical studies indicate that Arg is a nutritionally essential amino acid (AA) for spermatogenesis, embryonic survival, fetal and neonatal growth, as well as maintenance of vascular tone and hemodynamics. Moreover, a growing body of evidence clearly indicates that dietary supplementation or intravenous administration of Arg is beneficial in improving reproductive, cardiovascular, pulmonary, renal, gastrointestinal, liver and immune functions, as well as facilitating wound healing, enhancing insulin

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“…13 In most cases, arginine and sodium benzoate are given, and a low-protein diet is supplied. [16][17][18][19][20][21] Only a few patients were given citrulline and sodium phenylbutyrate because in 2007 citrulline was registered as a food and not as a medicine. Sodium phenylbutyrate was registered as medicine in 2013.…”

Section: Treatmentmentioning

confidence: 99%

Diagnosis and treatment of urea cycle disorder in Japan

Nakamura

Kido

Mitsubuchi

et al. 2014

Pediatrics International

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Urea cycle disorder (UCD) is an inborn error of the metabolic pathway producing urea from ammonia, which occurs primarily in the liver. Decreased excretion of nitrogen in the urea cycle due to deficiency of carbamoyl phosphate synthase I (CPSI), ornithine transcarbamylase (OTC), argininosuccinate synthase (ASS), argininosuccinate lyase (ASL), and N-acetyl glutamate synthase (NAGS) causes hyperammonemia. We examined the clinical manifestations, treatment, and prognosis of 177 patients with UCD from January 1999 to March 2009 in Japan. Compared with a previous study conducted in Japan, a larger number of patients survived without mental retardation, even when the peak blood ammonia was >360 μmol/L. In those with peak blood ammonia >360 μmol/L, an indicator of poor prognosis, the frequency of convulsions, mental retardation, brain abnormality on magnetic resonance imaging, hemodialysis, liver transplantation, and intake of non-protein formulas was significantly higher than in those with peak blood ammonia <360 μmol/L. In this article, we have reported the current state of UCD to evaluate prognosis and its relationship with peak blood ammonia and hemodialysis.Key words carbamoyl phosphate synthase I deficiency, hemodialysis, hyperammonemia, liver transplantation, ornithine transcarbamylase deficiency.The urea cycle is a pathway by which urea is produced from ammonia primarily in the liver (Fig. 1). 1 It is composed of four amino acids, namely ornithine, citrulline, argininosuccinic acid, and arginine. Citrulline is composed of ornithine and carbamoyl phosphate, and argininosuccinic acid is composed of citrulline and aspartic acid. Argininosuccinic acid is decomposed into fumaric acid and arginine, and arginine is disassembled into ornithine and urea. Ammonia is detoxified during the urea cycle to produce urea. Two nitrogen atoms in urea originate from aspartic acid and carbamoyl phosphate. Urea cycle disorder (UCD) is an inborn error of this metabolic pathway. Decreased excretion of nitrogen in the urea cycle due to deficiency of carbamoyl phosphate synthase (CPSI), ornithine transcarbamylase (OTC), argininosuccinate synthase (ASS), argininosuccinate lyase (ASL), arginase (ARG) and N-acetyl glutamate synthase (NAGS) causes hyperammonemia.1-3 Additionally, N-acetyl glutamic acid is essential to the activity of CPSI. Decrease in N-acetyl glutamic acid secondary to abnormality of NAGS results in UCD, which causes hyperammonemia. CPSI and OTC are found in the mitochondria, and other enzymes are located outside of it. In citrin deficiency and lysinuric protein intolerance, the activity of the urea cycle decreases to cause hyperammonemia.There are many reports on the long-term prognosis of UCD patients in Japan and other countries, [3][4][5][6][7][8][9][10][11][12] including one by us on long-term prognosis and treatment of UCD patients. 13 As with the previous studies, we found that the prognosis and neurological symptoms of UCD patients improved with early treatment. Furthermore, hemodialysis was performed in UC...

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Effects of arginine treatment on nutrition, growth and urea cycle function in seven Japanese boys with late-onset ornithine transcarbamylase deficiency

Abstract: Arginine treatment is able to reduces attacks of hyperammonemia in boys with late-onset OTCD and to increase their growth.

Cited by 27 publications

References 31 publications

Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision

Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision

Arginine metabolism and nutrition in growth, health and disease

Diagnosis and treatment of urea cycle disorder in Japan

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