AB017. Gene panel study for target metabolic diseases of newborn screening in Japan
Newborn Screening, Inborn Errors of Metabolism

AB017. Gene panel study for target metabolic diseases of newborn screening in Japan

Hideo Sasai1, Ryoji Fujiki2, Osamu Ohara2, Yoko Nakajima3, Tetsuya Ito3, Masahisa Kobayashi4, Go Tajima5, Osamu Sakamoto6, Shiro Matsumoto7, Kimitoshi Nakamura7, Takashi Hamazaki8, Yuki Hasegawa9, Hironori Kobayashi9, Toshiyuki Fukao1

1Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan;2Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan;3Department of Pediatrics, School of Medicine, Fujita Health University, Toyoake, Japan;4Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan;5Division of Neonatal Screening, NCCHD, Tokyo, Japan;6Department of Pediatrics, Tohoku University School of Medicine, Miyagi, Japan;7Department of Pediatrics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;8Department of Pediatrics, Osaka City Graduate School of Medicine, Osaka, Japan;9Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Japan

Background: Newborn screening (NBS) using tandem mass spectrometry has been performed since 2014 in all over Japan and the target metabolic diseases (TMDs) increased from 4 to at least 17 diseases. Molecular diagnosis for TMDs is not commercially available in Japan and until recently such molecular analyses were mainly performed by pediatricians with “volunteer spirits”. To change the situation, we designed and conducted molecular diagnosis for TMDs using a gene panel.

Methods: We designed a gene panel, which consists of more than 60 genes covering the TMDs and the related diseases. This research was financially supported by Japan Agency for Medical Research and Development. DNA was purified from patients’ blood at Gifu University and the gene panel analysis was performed at Kazusa DNA Research Institute using the MiSeq or NextSeq (Illumina®). Sanger sequencing was performed to confirm the detected mutations. Pediatric coauthors in this study are experts responsible to make mutation reports.

Results: We analyzed 138 patients who were positively screened during three years (January 2014 to March 2017) and 44 patients who were diagnosed before that period. The number of patients with TMDs detected by NBS was as follows: propionic acidemia [35], hyperphenylalaninemia [19], methylmalonic acidemia [17], VLCAD deficiency [15], Maple syrup urine disease [13], methylcrotonylglycinuria [13], galactosemia [10], primary systemic carnitine deficiency [9], MCAD deficiency [8], and others [43]. In most cases, we could find the gene mutations in their corresponding genes and found some common mutations for some TMDs in a Japanese population.

Conclusions: Clinical course and severity may differ among patients in some TMDs. One major factor to determine clinical phenotype is of course genotype. Hence, it is important to follow up mutation-defined patients to evaluate efficacy of treatment and management. We will individualize clinical guidelines by genotypes in some TMDs soon.

Keywords: Newborn screening (NBS); target metabolic diseases (TMDs); gene panel

doi: 10.21037/atm.2017.s017

Cite this article as: Sasai H, Fujiki R, Ohara O, Nakajima Y, Ito T, Kobayashi M, Tajima G, Sakamoto O, Matsumoto S, Nakamura K, Hamazaki T, Hasegawa Y, Kobayashi H, Fukao T. Gene panel study for target metabolic diseases of newborn screening in Japan. Ann Transl Med 2017;5(Suppl 2):AB017. doi: 10.21037/atm.2017.s017

Article Options

Download Citation

Share