Molecular and clinical analyses of Japanese patients with carbamoylphosphate synthetase 1 (CPS1) deficiency

J Hum Genet. 2007;52(4):349-354. doi: 10.1007/s10038-007-0122-9.

Keiji Kurokawa ¹, Tohru Yorifuji ², Masahiko Kawai ¹, Toru Momoi ³, Hironori Nagasaka ⁴, Masaki Takayanagi ⁴, Keiko Kobayashi ⁵, Makoto Yoshino ⁶, Tomoki Kosho ⁷, Masanori Adachi ⁸, Harumi Otsuka ⁹, Shigenori Yamamoto ¹⁰, Toshiaki Murata ¹¹, Akihito Suenaga ¹², Tsutomu Ishii ¹³, Kihei Terada ¹⁴, Naoto Shimura ¹⁵, Kohji Kiwaki ¹⁶, Haruo Shintaku ¹⁷, Masaru Yamakawa ¹⁸, Hiroki Nakabayashi ¹⁹, Yosuke Wakutani ²⁰, Tatsutoshi Nakahata ¹

Affiliations

1 Department of Pediatrics, Kyoto University Hospital, 54 Shogoin Sakyo, Kyoto, 606-8507, Japan.
2 Department of Pediatrics, Kyoto University Hospital, 54 Shogoin Sakyo, Kyoto, 606-8507, Japan. [email protected].
3 Department of Pediatrics, Japanese Red Cross Society, Wakayama Medical Center, Wakayama, Japan.
4 Division of Metabolism, Chiba Children's Hospital, Chiba, Japan.
5 Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
6 Department of Pediatrics, Kurume University School of Medicine, Kurume, Japan.
7 Division of Clinical and Molecular Genetics, Shinshu University Hospital, Matsumoto, Japan.
8 Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
9 Department of Neonatology, Chiba Municipal Kaihin Hospital, Chiba, Japan.
10 Department of Pediatrics, Shimoshizu National Hospital, Chiba, Japan.
11 Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
12 Department of Internal Medicine, Kitakyushu Municipal Yahata Hospital, Kitakyushu, Japan.
13 Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
14 Department of Pediatrics, Kawasaki Medical School, Kurashiki, Japan.
15 Department of Pediatrics, Dokkyo University School of Medicine, Tochigi, Japan.
16 Department of Pediatrics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
17 Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan.
18 Department of Pediatrics, Kobe City General Hospital, Kobe, Japan.
19 Department of Pediatrics, Nihon University Surugadai Hospital, Tokyo, Japan.
20 Department of Neurology, Institute of Neurological Sciences, Tottori University, Yonago, Japan.

PMID: 17310273 DOI: 10.1007/s10038-007-0122-9

Abstract

Carbamoylphosphate synthetase I deficiency (CPS1D) is a urea-cycle disorder characterized by episodes of life-threatening hyperammonemia. Correct diagnosis is crucial for patient management, but is difficult to make from clinical presentation and conventional laboratory tests alone. Enzymatic or genetic diagnoses have also been hampered by difficult access to the appropriate organ and the large size of the gene (38 exons). In this study, in order to address this diagnostic dilemma, we performed the largest mutational and clinical analyses of this disorder to date in Japan. Mutations in CPS1 were identified in 16 of 18 patients with a clinical diagnosis of CPS1D. In total, 25 different mutations were identified, of which 19 were novel. Interestingly, in contrast to previous reports suggesting an extremely diverse mutational spectrum, 31.8% of the mutations identified in Japanese were common to more than one family. We also identified two common polymorphisms that might be useful for simple linkage analysis in prenatal diagnosis. The accumulated clinical data will also help to reveal the clinical presentation of this rare disorder in Japan.

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