Neurological Features in KCNJ11 PNDM Reflect Expression of the KCNJ11 Gene in the Brain and Vary according to Genotype.
Impact of Sulphonylureas on the Neurological Phenotype in KCNJ11 PNDM and Generating Mechanistic Hypotheses from the Rodent Model.
Another possible reason for the incomplete CNS response to sulphonylurea treatment in people with KCNJ11 PNDM is that therapeutic concentrations of sulphonylurea are not achieved in the human CSF.
The patient was managed in between acute episodes with insulin for PNDM and pancreatic enzymes replacement therapy and daily oral prophylactic antibiotic.
She presented with PNDM and cyclic neutropenia at six-weeks of age.
WRS is the most common cause of PNDM in areas of high consanguinity.
The reason why certain mutations within the [K.sub.ATP] channel give rise to TNDM while others result in PNDM
is unknown, but changes in pancreatic beta cell turnover or compensation at the level of the beta cell or whole body that is able to overcome the effects of these genes may be possible explanations .
In summary, we present the cases of two Puerto Rican children, each with a de novo KCNJ/Kir6.2 activating mutation causing PNDM
. The children were able to stop insulin therapy and continue to thrive on SU.
The extent of membrane hyperpolarization caused by each mutation can explain the spectrum of variation of the clinical phenotype of the disease, ranging from TNDM (16) to PNDM
with neurological complications (developmental delay, epilepsy and neonatal diabetes syndrome) (15).
The PNDM is a group affecting 40-50% cases with no remission.7 Defining genetic etiology of this rare condition has not only given insights into clinical classification and disease mechanism, but has also influenced treatment.8 Mutations of the KCNJ11 gene have been identified as the most common genetic etiology in patients with PNDM.9 The KCNJ11 gene (present on chromosome 11) is comprised of 3409 base pairs and has a single exon flanked by two introns.10 There are 5 splice variants of this gene (ENSEMBL ID: ENSG00000187486).
Identification of genetic polymorphism in KCNJ11 gene is important in the diagnosis of NDM.11 Mutations in KCNJ11 and ABCC8 genes which encode the Kir6.2 and SUR1 subunits of the pancreatic ATP-sensitive potassium channel respectively have been implicated in the genesis of PNDM.9