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Long-term outcome and intervention of urea cycle disorders in Japan

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Urea cycle disorders (UCDs) are one of the most frequently inherited metabolic diseases in Japan, with an estimated prevalence of 1 per 50,000 live births. Here, we investigated the clinical manifestations, treatment, and prognosis of 177 patients with UCDs who were evaluated and treated from January 1999 to March 2009. These included 77 cases of neonatal-onset UCDs and 91 cases of late-onset UCDs. The most common UCD was ornithine transcarbamylase deficiency (OTCD), which accounted for 116 out of 177 patients. This result is similar to a previous study performed between 1978 and 1995 in Japan: OTCD accounted for about two-thirds of the total number of UCD cases. We studied the relationship between prognosis and the peak blood ammonia level at the onset in 151 UCD patients. Compared with a previous survey conducted in Japan, we found that a greater number of patients survived without any mental retardation despite their peak blood ammonia levels being greater than 360 μmol/l. The 5-year survival rate of patients with OTCD improved to 86% for those with the neonatal-onset type and to 92% for those with the late-onset type. We hypothesize that the increased survival rate is due to early diagnosis and better treatments that are now available in Japan. It is very important to diagnose and treat UCDs, especially OTCD, when the blood ammonia levels in patients are low. The outcome in patients with low blood ammonia levels was better than that in patients with high blood ammonia levels.

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Acknowledgments

This study was supported in part by a Grant-in-Aid for the Global COE Program from the Japanese Society for the Promotion of Science and Ministry of Education, Culture, Sports, Science and Technology; a Grant-in-Aid for Pediatric Research from the Ministry of Health, Labor and Welfare; and a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology.

We thank all 668 institutions and, in particular, the 87 institutions that kindly provided us with useful clinical information on patients with urea cycle disorders. We are very grateful to Mari Kimura and Asuka Sakamoto for their help in survey analysis. We express our gratitude to Professor Takahiko Katoh at the Department of Public Health, Kumamoto University for critical analysis of the statistical methods.

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Authors and Affiliations

  1. Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto City, Kumamoto Prefecture, 860-8556, Japan

    Jun Kido, Kimitoshi Nakamura, Hiroshi Mitsubuchi & Fumio Endo

  2. Division of Pediatrics, Sendai City Hospital, Sendai, Japan

    Toshihiro Ohura

  3. Division of Emergency and General Medicine, Chiba Children’s Hospital, Chiba, Japan

    Masaki Takayanagi

  4. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

    Masafumi Matsuo

  5. Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan

    Makoto Yoshino

  6. School of Nursing, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193, Japan

    Yosuke Shigematsu

  7. Department of Pediatric Endocrinology and Metabolism, Children’s Medical Center, Osaka City General Hospital, Osaka, Japan

    Tohru Yorifuji

  8. Department of Transplantation Surgery, National Center for Child Health and Development, Tokyo, Japan

    Mureo Kasahara

  9. Department of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo, Japan

    Reiko Horikawa

Authors
  1. Jun Kido
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  2. Kimitoshi Nakamura
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  3. Hiroshi Mitsubuchi
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  4. Toshihiro Ohura
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  5. Masaki Takayanagi
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  6. Masafumi Matsuo
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  7. Makoto Yoshino
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  8. Yosuke Shigematsu
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  9. Tohru Yorifuji
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  10. Mureo Kasahara
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  11. Reiko Horikawa
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  12. Fumio Endo
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Corresponding author

Correspondence to Kimitoshi Nakamura.

Additional information

Communicated by: Claude Bachmann

Competing interest: None declared.

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Kido, J., Nakamura, K., Mitsubuchi, H. et al. Long-term outcome and intervention of urea cycle disorders in Japan. J Inherit Metab Dis 35, 777–785 (2012). https://doi.org/10.1007/s10545-011-9427-0

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  • DOI: https://doi.org/10.1007/s10545-011-9427-0

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