KCNJ11 gene encodes Kir6.2, subunit of the β-cell ATP-dependent K-channel
(made up of 4 Kir6.2 and 4 sulfonylurea receptor 1 subunits); its heterozygous
activating mutation is a frequent cause of PNDM. Our 20y old pt was
the only child born from healthy unrelated parents (BW 2.3Kg, L 48cm). High
plasma glucose (PG) (10-16.7mmol/l) and glycosuria (no ketonuria) appeared
at 2d of life reaching 33.3mmol/l at 12d. Despite the progressive PG increase
and low fasting C-peptide (Cp) (149pmol/l at 12d, nv 178-680), she showed
good health conditions and regular weight gain until 35d old. Insulin (Ins) (1
IU/Kg/d) was started at 37d of life, because of ketonuria and failure to thrive
(PG 32mmol/l). Ins/Kg/d, progressively reduced, was stopped at 2.5y because
of good metabolic control and frequent hypoglycaemic events. Cp decreased
from 149pmol/l (at 12d) to undetectable value (8.5m old) with a subsequent
increase (119pmol/l, at 20m). At diagnosis anti-Ins and anti-β-cell antibodies
(AA) were negative. OGTT at 2.9y: normal fasting PG (4.5mmol/l) and Ins
(47.3pmol/l), impaired GT (8.4mmol/l at 120‘), blunted Ins peak (87.5pmol/
l). HbA1c constantly <7%. At 4.1y and 7.5y: PG at 120‘ 7.2 and 11.7mmol/l,
respectively. At 8y, Ins therapy was restored (0.8 U/kg/d) having high HbA1c
values (10.2-11.5%) and anti-gliadin AA were detected; asymptomatic celiac
disease was confirmed by biopsy. At 19.7y, IVGTT showed low basal
(231pmol/l, nv 281-1317pmol/l) and peak (265pmol/l) Cp. A transition G->A
at position 602, with a His->Arg at codon 201 (R201H), was identified in the KCNJ11 gene (mutation absent in parents). Ins was progressively reduced and
stopped within 11d and glibenclamide (Gl) administered (increasing dose:
after 3m 0.39mg/Kg/d, no HbA1c increase). After 4w on Gl, Cp raised to
1158pmol/l. This mutation is the most frequent genetic defect associated with
PNDM: no one of 9 described pts currently older than 3y experienced honey
moon, 8/9 being constantly Ins-treated (1 adult pt on tolbutamide since childhood).
Our data indicate that this mutation can confer a broad range of clinical
presentation and prompts the KCNJ11 gene analysis in all cases of ND