Van gen naar ziekte; neonatale diabetes mellitus en het KCNJ11-gen

- Neonatal diabetes mellitus (DM) is by definition diagnosed within the first 3 months of life and can be either transient (TNDM) or permanent (PNDM). Recently, activating mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the K_ATP channel, have been identified as a cause of TNDM, the main cause of PNDM, and the cause of a new syndrome: developmental delay, epilepsy and neonatal diabetes. Patients with neonatal DM are normally dependent on life-long insulin injections, but patients with neonatal DM due to a KCNJ11 mutation are able to achieve control with sulphonylurea tablets. The mutations are predominantly spontaneous but have also been described as due to autosomal dominant inheritance and paternal mosaicism. Mutations at codon 201 and 59 are thus far the most prevalent. Because mutated K_ATP channels do not close in response to ATP, the β-cell membrane is hyperpolarised and insulin secretion does not occur. Mutated K_ATP channels in muscle, nerve and brain are responsible for the neurological symptoms.

Ned Tijdschr Geneeskd. 2005;149:2732-6