Presented By:

1,2Hideo Sasai M.D.,Ph.D., 1Yasuhiko Ago M.D.,1Hideki Matsumoto M.D., 1,2,3Hiroki Otsuka M.D., 4Junichi Hosokawa M.D.,Ph.D., 4Ryoji Fujiki Ph.D., 4Osamu Ohara Ph.D., 5Yoko Nakajima M.D.,Ph.D., 5Tetsuya Ito M.D.,Ph.D., 6Keiichi Hara M.D.,Ph.D., 7Masahisa Kobayashi M.D.,Ph.D., 8Go Tajima M.D.,Ph.D., 9Osamu Sakamoto M.D.,Ph.D., 10Jun Kido M.D., Ph.D., 10Shirou Matsumoto M.D.,Ph.D., 10Kimitoshi Nakamura M.D.,Ph.D., 11Takashi Hamazaki M.D.,Ph.D., 12Hironori Kobayashi M.D.,Ph.D., 12Yuki Hasegawa M.D.,Ph.D., 1,2Toshiyuki Fukao M.D.,Ph.D.

1Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
2Division of Clinical Genetics, Gifu University Hospital, Gifu, Japan.
3Department of Neonatal Medicine, Gifu Prefectural General Medical Center, Gifu, Japan;
4Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan.
5Department of Pediatrics, School of Medicine, Fujita Health University, Toyoake, Japan.
6Department of Pediatrics, Kure Medical Center, Kure, Japan.
7Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
8Division of Neonatal Screening, NCCHD, Tokyo, Japan.
9Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
10Department of Pediatrics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
11Department of Pediatrics, Faculty of Medicine, Osaka City University, Osaka, Japan.
12Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Japan.

Corresponding author: Hideo Sasai, Department of Pediatrics, Graduate School of Medicine, Gifu University; 1-1

Yanagido, Gifu, 501-1194, Japan; Tel +81-58-230-6386; FAX +81-58-230-6387; E-mail:

Background: Public newborn screening (NBS) using tandem mass was initiated nationwide in Japan in 2014. Since then we have been conducting a follow-up study with identification of gene mutations using a gene panel for NBS target inherited metabolic diseases (TMD) for 5 years. TMD included fatty acid oxidation defects (FAODs) as follow: VLCAD deficiency, MCAD deficiency, primary systemic carnitine deficiency, Glutaric acidemia type 2, CPT2 deficiency, CPT1 deficiency, TFP deficiency and CACT deficiency. The purpose of this study is to accumulate phenotype-genotype correlation for TMD in Japan and to individualize clinical guidelines in relation with their mutations.

Methods: We designed a gene panel covering the TMDs and the related diseases. Gene panel analysis was performed at Kazusa DNA Research Institute. Informed consents for gene analysis and approval for participation of follow-up study were obtained from parents. This research was supported by Japan Agency for Medical Research and Development.

Results: More than 340 cases were enrolled in this gene panel study for five years (January 2014 to March 2019). Among them, the number of patients with TMDs detected by NBS were 260 cases in total, 65 cases of FAODs: VLCAD deficiency (19), MCAD deficiency (16), primary systemic carnitine deficiency (12), Glutaric acidemia type 2 (9), CPT2 deficiency (5), CPT1 deficiency (3), TFP deficiency (1). In most cases, we could find the gene mutations in their corresponding genes. We have also been conducting clinical follow-up studies.

Discussion: In some TMDs, clinical course and severity may vary from patient to patient. One major factor determining the clinical phenotype is, of course, the genotype. It is therefore important to follow up patients with defined mutations to evaluate the effectiveness of treatment and management. In the near future, we plan to personalize clinical guidelines by genotyping of several TMDs.

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