Platform for conformation and screening of BCKDK deficiency; potentially treatable form of autism with epilepsy

• Project/Area Number: 25461532
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: Sakamoto Osamu 東北大学, 医学(系)研究科(研究院), 准教授 (20333809)
• Co-Investigator(Kenkyū-buntansha): OHURA Toshihiro 東北大学, 医学系研究科, 非常勤講師 (10176828) ; UEMATSU Mitsugu 東北大学病院, 講師 (90400316)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 分岐鎖アミノ酸・ / 自閉症 / 新生児マススクリーニング / 分岐鎖アミノ酸 / アミノ酸代謝異常症 / てんかん

Outline of Final Research Achievements

Autism spectrum disorders are a genetically heterogeneous. Reentry inactivating mutations in the BCKDK gene, which codes for the kinase responsible for the negative regulation of the branched-chain α-keto acid dehydrogenase complex (BCKD), have been associated with a form. These patients and bckdk knockout mice showed abnormal plasma amino acid profiles (reduced BCAA values). These facts suggest that BCKDK deficiency might be screened biochemically. So we planned to establish the platform for conformation and screening of BCKDK deficiency.
Mutation analysis was performed to a case who showed slightly reduced BCAA values and marginal mental retardation. No substitution was found in BCKDK gene.
More than 130,000 newborns in Miyagi, Aomori and Yamagata prefecture were checked by newborn mas-screening among three years. The number of cases showed the low value of isoleucine + leucine (<45 nmlo/L) was three. All of them was very low weight infants and showed normal value by second tests.

Research Products

• [Journal Article] Phenotypic Variability and Newly Identified Mutations of the <i>IVD </i>Gene in Japanese Patients with Isovaleric Acidemia (2015)
  • Author(s): Sakamoto O, Arai-Ichinoi N, Mitsubuchi H, Chinen Y, Haruna H, Maruyama H, Sugawara H, Kure S.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 236 Issue: 2 Pages: 103-106
  • DOI: 10.1620/tjem.236.103
  • NAID: 130005072136
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] タンデムマスによる新生児マススクリーニングで発見されたコバラミン代謝異常症C型(CblC)の一例 (2015)
  • Author(s): 坂本修、市野井那津子、呉繁夫
  • Journal Title: 日本マススクリーニング学会誌 Volume: 25 Pages: 83-87
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] シトリン欠損による新生児肝内うっ滞症(Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency, NICCD)の診断と治療 (2015)
  • Author(s): 大浦敏博、坂本修
  • Journal Title: 日本マススクリーニング学会誌 Volume: 25 Pages: 11-15
• [Journal Article] Clinical characteristics and mutation analysis of propionic acidemia in Thailand (2014)
  • Author(s): Vatanavicharn N, Liammongkolkul S, Sakamoto O, Kamolsilp M, Sathienkijkanchai A, Wasant P.
  • Journal Title: World Journal of Pediatrics Volume: 10 Issue: 1 Pages: 64-68
  • DOI: 10.1007/s12519-014-0454-4
  • Peer Reviewed
• [Journal Article] Early replacement therapy in a first Japanese case with autosomal recessive guanosine triphosphate cyclohydrolase I deficiency with a novel point mutation (2014)
  • Author(s): Hiroki Sato, Mitsugu Uematsu, Wakaba Endo, Tojo Nakayam, Tomoko Kobayashi, Naomi Hino-Fukuyo, Osamu Sakamoto, Haruo Shintaku, Shigeo Kure
  • Journal Title: Brain Dev. Volume: 36 Issue: 3 Pages: 268-271
  • DOI: 10.1016/j.braindev.2013.04.003
  • Peer Reviewed
• [Journal Article] Successful treatment of cardiac failure due to cardiomyopathy in propionic acidemia by cardiac resynchronization therapy and hemodialysis in a young adult. (2014)
  • Author(s): Kimura M, Wakayama Y, Sakamoto O, Kawano K, Ohura T, Kure S.
  • Journal Title: Open Journal of Pediatrics Volume: 4 Issue: 01 Pages: 79-83
  • DOI: 10.4236/ojped.2014.41011
  • Peer Reviewed / Open Access
• [Journal Article] Reduction in Glutamine/Glutamate Levels in the Cerebral Cortex after Adrenocorticotropic Hormone Therapy in Patients with West Syndrome (2014)
  • Author(s): Munakata M, Togashi N, Sakamoto O, Haginoya K, Kobayashi Y, Onuma A, Iinuma K, Kure S.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 232 Issue: 4 Pages: 277-283
  • DOI: 10.1620/tjem.232.277
  • NAID: 130004460120
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] Interstitial lung disease in two brothers with novel compound heterozygous ABCA3 mutations (2013)
  • Author(s): Kitazawa H, Moriya K, Niizuma H, Kawano K, Saito-Nanjo Y, Uchiyama T, Rikiishi T, Sasahara Y, Sakamoto O, Setoguchi Y, Kure S
  • Journal Title: Eur J Pediatr Volume: 172(7) Issue: 7 Pages: 953-7
  • DOI: 10.1007/s00431-013-1977-8
  • Peer Reviewed
• [Journal Article] 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. (2013)
  • Author(s): Imataka G, Sakamoto O, Yamanouchi H, Yoshihara S, Omura-Hasegawa Y, Tajima G, Arisaka O
  • Journal Title: Cell Biochem Biophys Volume: 67(1) Issue: 1 Pages: 185-7
  • DOI: 10.1007/s12013-013-9532-9
  • Peer Reviewed
• [Presentation] タンデムマスによる新生児マススクリーニングで発見されたコバラミン代謝異常症C型(CblC)の一例 (2015)
  • Author(s): 坂本修、市野井那津子、呉繁夫
  • Organizer: 第57回日本先天代謝異常学会
  • Place of Presentation: 大阪（大阪国際会議場）
  • Year and Date: 2015-11-12