Citrulline for urea cycle disorders in Japan

Tanaka, Kenichi; Nakamura, Kimitoshi; Matsumoto, Shirou; Kido, Jun; Mitsubuchi, Hiroshi; Ohura, Toshihiro; Endo, Fumio

doi:10.1111/ped.13163

Cited by 10 publications

(17 citation statements)

References 16 publications

(31 reference statements)

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“…Furthermore, patients with clinically asymptomatic OTCD showed mildly elevated hepatic enzyme levels and International Normalized Ratio. In a most recent Japanese cohort of 33 OTCD patients, mean transaminase levels were mildly elevated (AST 47.6 and 58.5 IU/L and ALT 38.1 and 70.9 IU/L in males and females, respectively), which suggests chronic liver dysfunction (Tanaka et al 2016).…”

Section: Ornithine Transcarbamylase Deficiency (Otcd)mentioning

confidence: 97%

Liver involvement in urea cycle disorders: a review of the literature

Bigot¹,

Tchan²,

Thoreau³

et al. 2017

J of Inher Metab Disea

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Urea cycle disorders (UCDs) are inborn errors of metabolism of the nitrogen detoxification pathway and encompass six principal enzymatic deficiencies. The aging of UCD patients leads to a better knowledge of the long-term natural history of the condition and to the reporting of previously unnoticed manifestations. Despite historical evidence of liver involvement in UCDs, little attention has been paid to this organ until recently. Hence, we reviewed the available scientific evidence on acute and chronic liver dysfunction and liver carcinogenesis in UCDs and discuss their pathophysiology. Overall, liver involvement, such as acute liver failure or steatotic-like disease, which may evolve toward cirrhosis, has been reported in all six main UCDs. Excessive glycogen storage is also a prominent histologic feature, and hypoglycemia has been reported in citrin deficiency. Hepatocarcinomas seem frequent in some UCDs, such as in citrin deficiency, and can sometimes occur in non-cirrhotic patients. UCDs may differ in liver involvement according to the enzymatic deficiency. Ornithine transcarbamylase deficiency may be associated more with acute liver failure and argininosuccinic aciduria with chronic liver failure and cirrhosis. Direct toxicity of metabolites, downstream metabolic deficiencies, impaired tricarboxylic acid cycle, oxidative stress, mitochondrial dysfunction, energy deficit, and putative toxicity of therapies combine in various ways to cause the different liver diseases reported.

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Section: Ornithine Transcarbamylase Deficiency (Otcd)mentioning

confidence: 97%

Liver involvement in urea cycle disorders: a review of the literature

Bigot¹,

Tchan²,

Thoreau³

et al. 2017

J of Inher Metab Disea

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“…9 Citrulline is effective in treating patients with OTC and CPS1 deficiency (OTCD and CPSD), because it is lacking in these patients and acts as a supplier of arginine in the urea cycle. 10,11 In metabolic crises, hemodialysis or hemodiafiltration are more effective than peritoneal dialysis for rapidly eliminating blood ammonia. 12,13 Liver transplantation (LT) is the most effective treatment to prevent further hyperammonemic crises and to improve the quality of life.…”

Section: Introductionmentioning

confidence: 99%

“…Arginine is an important therapy in all UCDs except ARG1 deficiency (ARGD), because of impaired arginine biosynthesis in these individuals 9 . Citrulline is effective in treating patients with OTC and CPS1 deficiency (OTCD and CPSD), because it is lacking in these patients and acts as a supplier of arginine in the urea cycle 10,11 . In metabolic crises, hemodialysis or hemodiafiltration are more effective than peritoneal dialysis for rapidly eliminating blood ammonia 12,13 .…”

Section: Introductionmentioning

confidence: 99%

Long‐term outcome of urea cycle disorders: Report from a nationwide study in Japan

Kido

Matsumoto

Häberle

et al. 2021

J of Inher Metab Disea

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Urea cycle disorders (UCDs) are inherited metabolic disorders with impaired nitrogen detoxification caused by defects in urea cycle enzymes. They often manifest with hyperammonemic attacks resulting in significant morbidity or death. We performed a nationwide questionnaire-based study between January 2000 and March 2018 to document all UCDs in Japan, including diagnoses, treatments, and outcomes. A total of 229 patients with UCDs were enrolled in this study: 73 males and 53 females with ornithine transcarbamylase deficiency (OTCD), 33 patients with carbamoylphosphate synthetase 1 deficiency, 48 with argininosuccinate synthetase deficiency, 14 with argininosuccinate lyase deficiency, and 8 with arginase deficiency. Survival rates at 20 years of age of male and female patients with late-onset OTCD were 100% and 97.7%, respectively. Blood ammonia levels and time of onset had a significant impact on the neurodevelopmental outcome (P < .001 and P = .028, respectively). Hemodialysis and liver transplantation did not prevent poor neurodevelopmental outcomes.While treatment including medication, hemodialysis, and liver transplantation may aid in decreasing blood ammonia and/or preventing severe hyperammonemia, a blood ammonia level ≥ 360 μmol/L was found to be a significant indicator for a poor neurodevelopmental outcome. In conclusion,

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“…Enhanced citrulline suggests uric acid failure, which may correlate with liver cirrhosis or hepatic coma. The urea cycle is related to the citric acid cycle through fumaric acid . In liver cells, citrulline is transported from mitochondria to the cytoplasm and then reacts with aspartic acid to produce argininosuccinic acid.…”

Section: Discussionmentioning

confidence: 99%