Novel mutations in five Japanese patients with 3-methylcrotonyl-CoA carboxylase deficiency

Mitsugu Uematsu, Osamu Sakamoto, Noriko Sugawara, Naonori Kumagai, Tetsuji Morimoto, Seiji Yamaguchi, Yuki Hasegawa, Hironori Kobayashi, Kenji Ihara, Makoto Yoshino, Yoriko Watanabe, Takahiro Inokuchi, Takato Yokoyama, Kohji Kiwaki, Kimitoshi Nakamura, Fumio Endo, Shigeru Tsuchiya, Toshihiro Ohura

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16 Citations (Scopus)


Isolated 3-methylcrotonyl-CoA carboxylase (MCC) deficiency appears to be the most frequent organic aciduria detected in tandem mass spectrometry (MS/MS) screening programs in the United States, Australia, and Europe. A pilot study of newborn screening using MS/MS has recently been commenced in Japan. Our group detected two asymptomatic MCC deficiency patients by the pilot screening and collected data on another three MCC deficiency patients to study the molecular bases of the MCC deficiency in Japan. Molecular analyses revealed novel mutations in one of the causative genes, MCCA or MCCB, in all five of the patients: nonsense and frameshift mutations in MCCA (c.1750C > T/c.901_902delAA) in patient 1, nonsense and frameshift mutations in MCCB (c.1054_1055delGG/c.592C > T) in patient 2, frameshift and missense mutations in MCCB (c.1625_1626insGG/c.653_654CA > TT) in patient 3, a homozygous missense mutation in MCCA (c.1380T > G/ 1380T > G) in patient 4, and compound heterozygous missense mutations in MCCB (c.569A > G/ c.838G > T) in patient 5. No obvious clinical symptoms were observed in patients 1, 2, and 3. Patient 4 had severe neurological impairment and patient 5 developed Reye-like syndrome. The increasing use of MS/MS newborn screening in Japan will further clarify the clinical and genetic heterogeneity among patients with MCC deficiency in the Japanese population.

Original languageEnglish
Pages (from-to)1040-1043
Number of pages4
JournalJournal of Human Genetics
Issue number12
Publication statusPublished - 2007 Dec


  • 3-Methylcrotonyl-CoA carboxylase
  • Carnitine
  • Hyperammonemia
  • Newborn screening
  • Tandem mass spectrometry


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