TY - JOUR
T1 - Novel c.2216T > C (p.I739T) Mutation in Exon 13 and c.1481T > A (p.L494X) Mutation in Exon 8 of MUT Gene in a Female with Methylmalonic Acidemia
AU - Imataka, George
AU - Sakamoto, Osamu
AU - Yamanouchi, Hideo
AU - Yoshihara, Shigemi
AU - Omura-Hasegawa, Yuki
AU - Tajima, Go
AU - Arisaka, Osamu
PY - 2013/9
Y1 - 2013/9
N2 - We report herein a 1.5-year-old girl with methylmalonic acidemia (MMA) in whom two missense mutations were found: a novel I739T mutation located in exon 13 and the L494X mutation in exon 8. The results of organic acid test showed a pronounced increase in methylmalonate excretion with increased methylcitrate and 3-OH-propionate excretion, leading to a diagnosis of MMA, and Vitamin B12 administration was started. Analysis of the mut gene confirmed a T-to-A substitution at nucleotide position 1481 in exon 8 and a T-to-C substitution at nucleotide position 2216 in exon 13, leading to the amino acid isoleucine at position 739 being changed to threonine, resulting in c.2216T > C (p.I739T). The patient has now been on high-dose oral administration of Vitamin B12 and carnitine therapy (900 mg of levocarnitine chloride) for 5 years without experiencing further attacks, and her cognitive and motor development is normal. Further tests on residual enzyme activity, as well as experience with more cases, may shed light on the relationship between gene mutations and phenotypes in MMA.
AB - We report herein a 1.5-year-old girl with methylmalonic acidemia (MMA) in whom two missense mutations were found: a novel I739T mutation located in exon 13 and the L494X mutation in exon 8. The results of organic acid test showed a pronounced increase in methylmalonate excretion with increased methylcitrate and 3-OH-propionate excretion, leading to a diagnosis of MMA, and Vitamin B12 administration was started. Analysis of the mut gene confirmed a T-to-A substitution at nucleotide position 1481 in exon 8 and a T-to-C substitution at nucleotide position 2216 in exon 13, leading to the amino acid isoleucine at position 739 being changed to threonine, resulting in c.2216T > C (p.I739T). The patient has now been on high-dose oral administration of Vitamin B12 and carnitine therapy (900 mg of levocarnitine chloride) for 5 years without experiencing further attacks, and her cognitive and motor development is normal. Further tests on residual enzyme activity, as well as experience with more cases, may shed light on the relationship between gene mutations and phenotypes in MMA.
KW - Methylmalonic acidemia
KW - Vitamin B12
KW - l-Methylmalonyl-CoA mutase
UR - http://www.scopus.com/inward/record.url?scp=84883458878&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883458878&partnerID=8YFLogxK
U2 - 10.1007/s12013-013-9532-9
DO - 10.1007/s12013-013-9532-9
M3 - Article
C2 - 23479330
AN - SCOPUS:84883458878
VL - 67
SP - 185
EP - 187
JO - Cell Biochemistry and Biophysics
JF - Cell Biochemistry and Biophysics
SN - 1085-9195
IS - 1
ER -