TY - JOUR
T1 - Molecular and clinical features of KATP-channel neonatal diabetes mellitus in Japan
AU - Hashimoto, Yukiko
AU - Dateki, Sumito
AU - Hirose, Masakazu
AU - Satomura, Kenichi
AU - Sawada, Hirotake
AU - Mizuno, Haruo
AU - Sugihara, Shigetaka
AU - Maruyama, Koichi
AU - Urakami, Tatsuhiko
AU - Sugawara, Hidenori
AU - Shirai, Kenji
AU - Yorifuji, Tohru
N1 - Funding Information:
We thank the patients and their families who participated in the study and the physicians throughout Japan who referred those patients for this study. We also thank Drs Azumi Sakakibara, Rie Kawakita, Yuki Hosokawa, Rika Fujimaru (Osaka City General Hospital), Hideo Takatsuka (Nara Prefecture Western Medical Center), Chutaro Yamanaka (Tenri Hospital), Etsuo Igarashi (Ohara General Hospital), Yuko Nagaoki (St. Luke's International Hospital), Rika Usuda (Toyama Prefectural Central Hospital), Akihiko Miyauchi (Jichi University), Mitsukazu Mamada (Japanese Red Cross Society Wakayama Medical Center), Keiji Kurokawa (Shimada Municipal Hospital), and Toshiro Nakamura (Kumamoto Chuo Hospital) for helpful discussions. This work was supported in part by a Grant-in-Aid for Scientific Research to TY (15K09636) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. None of the authors has any potential conflicts of interest associated with this research.
Funding Information:
We thank the patients and their families who participated in the study and the physicians throughout Japan who referred those patients for this study. We also thank Drs Azumi Sakakibara, Rie Kawakita, Yuki Hosokawa, Rika Fujimaru (Osaka City General Hospital), Hideo Takatsuka (Nara Prefecture Western Medical Center), Chutaro Yamanaka (Tenri Hospital), Etsuo Igarashi (Ohara General Hospital), Yuko Nagaoki (St. Luke's International Hospital), Rika Usuda (Toyama Prefectural Central Hospital), Akihiko Miyauchi (Jichi University), Mitsukazu Mamada (Japanese Red Cross Society Wakayama Medical Center), Keiji Kurokawa (Shimada Municipal Hospital), and Toshiro Nakamura (Kumamoto Chuo Hospital) for helpful discussions. This work was supported in part by a Grant-in-Aid for Scientific Research to TY (15K09636) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Publisher Copyright:
© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2017/11
Y1 - 2017/11
N2 - Background: There are few reports pertaining to Asian patients with neonatal diabetes mellitus (NDM) caused by activating mutations in the ATP-sensitive potassium channel genes (KATP-NDM). Objectives: To elucidate the characteristics of Japanese patients with KATP-NDM. Methods: By the amplification and direct sequencing of all exons and exon-intron boundaries of the KCNJ11 and ABCC8 genes, 25 patients with KATP-NDM were identified from a total of 70 patients with NDM. Clinical data were collected from the medical charts. Results: Sixteen patients had mutations in KCNJ11 and nine in ABCC8. Eight novel mutations were identified; two in KCNJ11 (V64M, R201G) and six in ABCC8 (R216C, G832C, F1176L, A1263V, I196N, T229N). Interestingly, V64M caused DEND (developmental delay, epilepsy, neonatal diabetes) syndrome in our patient, while mutation of the same residue (V64G) had been reported to cause congenital hyperinsulinism. Mutations in ABCC8 were associated with TNDM (4/9) or isolated PNDM (5/9), whereas those in KCNJ11 were associated with more severe phenotypes, including DEND (3/16), iDEND (intermediate DEND, 4/16), or isolated PNDM (6/16). Switching from insulin to glibenclamide monotherapy was successful in 87.5% of the patients. Neurological improvement was observed in two patients, one with DEND (T293N) and one with iDEND (R50P) syndrome. Three others with iDEND mutations (R201C, G53D, and V59M) remained neurologically normal at 5, 1, and 4 years of age, respectively, with early introduction of sulfonylurea. Conclusion: Overall, clinical presentation of KATP-NDM in Japanese patients was similar to those of other populations. Early introduction of sulfonylurea appeared beneficial in ameliorating neurological symptoms.
AB - Background: There are few reports pertaining to Asian patients with neonatal diabetes mellitus (NDM) caused by activating mutations in the ATP-sensitive potassium channel genes (KATP-NDM). Objectives: To elucidate the characteristics of Japanese patients with KATP-NDM. Methods: By the amplification and direct sequencing of all exons and exon-intron boundaries of the KCNJ11 and ABCC8 genes, 25 patients with KATP-NDM were identified from a total of 70 patients with NDM. Clinical data were collected from the medical charts. Results: Sixteen patients had mutations in KCNJ11 and nine in ABCC8. Eight novel mutations were identified; two in KCNJ11 (V64M, R201G) and six in ABCC8 (R216C, G832C, F1176L, A1263V, I196N, T229N). Interestingly, V64M caused DEND (developmental delay, epilepsy, neonatal diabetes) syndrome in our patient, while mutation of the same residue (V64G) had been reported to cause congenital hyperinsulinism. Mutations in ABCC8 were associated with TNDM (4/9) or isolated PNDM (5/9), whereas those in KCNJ11 were associated with more severe phenotypes, including DEND (3/16), iDEND (intermediate DEND, 4/16), or isolated PNDM (6/16). Switching from insulin to glibenclamide monotherapy was successful in 87.5% of the patients. Neurological improvement was observed in two patients, one with DEND (T293N) and one with iDEND (R50P) syndrome. Three others with iDEND mutations (R201C, G53D, and V59M) remained neurologically normal at 5, 1, and 4 years of age, respectively, with early introduction of sulfonylurea. Conclusion: Overall, clinical presentation of KATP-NDM in Japanese patients was similar to those of other populations. Early introduction of sulfonylurea appeared beneficial in ameliorating neurological symptoms.
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U2 - 10.1111/pedi.12447
DO - 10.1111/pedi.12447
M3 - Article
C2 - 27681997
AN - SCOPUS:84994717913
VL - 18
SP - 532
EP - 539
JO - Pediatric Diabetes
JF - Pediatric Diabetes
SN - 1399-543X
IS - 7
ER -