Transient neonatal diabetes mellitus is associated with a recurrent (R201H) KCNJ11 (KIR6.2) mutation

Sulfonylurea treatment outweighs insulin therapy in short-term metabolic control of patients with permanent neonatal diabetes mellitus due to activating mutations of the KCNJ11 (KIR6.2) gene

“…The discovery that activating mutations of KCJN11 causing permanent or transient neonatal diabetes can respond to sulfonylureas [1, 2, 4-8] opened the possibility of treating patients who have this genetic defect with oral hypoglycaemic agents. In previous studies [4,9], this report and in unpublished observations (F. Barbetti), the Italian Study Group of Early-Onset Diabetes has identified 16 unrelated subjects with eight different KCNJ11 mutations. To date, one subject with KCNJ11-related transient/relapsing neonatal diabetes [4] and ten patients from the Italian cohort of KCNJ11-related permanent neonatal diabetes mellitus have been successfully transferred from insulin to sulfonylurea.…”

“…In previous studies [4,9], this report and in unpublished observations (F. Barbetti), the Italian Study Group of Early-Onset Diabetes has identified 16 unrelated subjects with eight different KCNJ11 mutations. To date, one subject with KCNJ11-related transient/relapsing neonatal diabetes [4] and ten patients from the Italian cohort of KCNJ11-related permanent neonatal diabetes mellitus have been successfully transferred from insulin to sulfonylurea. In regard to the five patients still receiving insulin therapy, three were only recently diagnosed, whilst the parents of the other two refused the sulfonylurea trial.…”

“…Cases with various KCNJ11 mutations (V59M, R201H [x 4], R201L, V333I) [1,2,[4][5][6][7][8] who were transferred to glibenclamide or other sulfonylureas have been previously published as single-case reports [2,[6][7][8], or as small-group (three patients) reports [5]. Our experience is valuable for at least three aspects.…”

Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype

“…The most common mutation, R201H, has now been reported in 20 patients [6,8,10,16], with none of the patients having neurological features. In contrast, of the 13 patients with the V59M mutation, ten (77%) have intermediate DEND syndrome [1,4,6,10].…”

“…These patients had mutations not seen in patients with isolated diabetes. Only three of 16 probands with a mutation at residue R201 had neurological symptoms, and all three patients had the less common R201C mutation [1,4,6,7,9,10,13,15,16]. Some patients with the V59M mutation have permanent neonatal diabetes with developmental delay but no epilepsy (intermediate DEND [I-DEND] syndrome) [1,4,6,10], whereas others have no reported neurological features [1,4].…”