Novel mutations in five Japanese patients with 3-methylcrotonyl-CoA carboxylase deficiency.
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.
Uematsu
Mitsugu
M
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
Sakamoto
Osamu
O
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
Sugawara
Noriko
N
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
Kumagai
Naonori
N
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
Morimoto
Tetsuji
T
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
Yamaguchi
Seiji
S
Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, Japan.
Hasegawa
Yuki
Y
Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, Japan.
Kobayashi
Hironori
H
Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, Japan.
Ihara
Kenji
K
Department of Pediatrics, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan.
Yoshino
Makoto
M
Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Japan.
Watanabe
Yoriko
Y
Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Japan.
Inokuchi
Takahiro
T
Research Institute of Medical Mass Spectrometry, Kurume University School of Medicine, 67 Asahimachi, Kurume, Japan.
Yokoyama
Takato
T
Department of Pediatrics, St Mary's Hospital, 422 Tsubukuhonmachi, Kurume, Japan.
Kiwaki
Kohji
K
Department of Pediatrics, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, Japan.
Nakamura
Kimitoshi
K
Department of Pediatrics, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, Japan.
Endo
Fumio
F
Department of Pediatrics, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, Japan.
Tsuchiya
Shigeru
S
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
Ohura
Toshihiro
T
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan. tohura@mail.tains.tohoku.ac.jp.
D019735:Carbon-Carbon Ligases / Q000172:deficiency / Q000235:genetics*; D016368:Frameshift Mutation; D006801:Humans; D007231:Infant, Newborn; D007564:Japan; D009154:Mutation; D020125:Mutation, Missense; D015997:Neonatal Screening / Q000379:methods*; D053719:Tandem Mass Spectrometry
D019735:Carbon-Carbon Ligases; C021573:methylcrotonoyl-CoA carboxylase