Molecular and clinical features of 13 cases of ATP-sensitive potassium channel neonatal diabetes mellitus

Abstract

Objective To elucidate the clinical characteristics and genotype-phenotype relationships of Chinese patients with neonatal diabetes mellitus (NDM) caused by ATP-sensitive potassium channel (KATP) gene mutations (KATP-NDM). Methods Total of 23 suspected patients with NDM were recruited from Peking Union Medical College Hospital. Amplification and direct sequencing of all exons and exon-intron boundaries of the KCNJ11 and ABCC8 gene were done for molecular genetic diagnosis. Patients with a definite diagnosis of KATP-NDM were switched from insulin injection to oral glibenclamide. Results Thirteen patients with KATP-NDM were identified, including 9 cases of KCNJ11-NDM and 4 cases of ABCC8-NDM. Four novel mutations of KATP were identified: 1 in KCNJ11 (I182M) and 3 in ABCC8 (Q211R,I585F, R653W). Among 9 patients with KCNJ11-NDM, 2 were transient NDM (TNDM) and 7 were permanent NDM (PNDM), and 3 of which had intermediate developmental delay, neonatal diabetes (iDEND syndrome). Four patients with ABCC8-NDM were all PNDM, 2 of them had iDEND syndrome. Switching from insulin to glibenclamide monotherapy was successful in 9 patients (69.2%). Conclusions Different clinical severities and treatment responses to sulfonylureas exist even among patients with the same mutation or with different amino acids at the same mutation site. Early diagnosis of KATP-NDM and initiation of sulfonylureas are of great importance in the prevention of neurological abnormalities in patients with iDEND syndrome. Key words: Neonatal diabetes mellitus; Adenosine triphosphate-sensitive potassium channel; Sulfonylureas