Permanent neonatal diabetes mellitus

Patients with permanent neonatal diabetes (PNDM) are permanently hyperglycemic within three months after the birth. Hyperglycemia can also be temporary and glucose levels can be normalized after three months. However, some patients remain diabetic and need permanent medication. In some cases the patients have neurological symptoms (e.g. weakness in muscles, delayed development or epilepsy). Differential diagnosis between PNDM and type 1 diabetes on the basis of clinical findings is not simple, since both of these diseases are associated with hyperglycemia and ketoacidosis. PNDM is usually diagnosed at a very young age (< 6 months) among patients having no HLA risk alleles and no autoantibodies characteristic for type 1 diabetes.

Etiology of PNDM was unknown until 2004 when mutations in the ATP-dependent K-Channels (the Kir6.2 (ABCC8) gene) were shown to cause permanent neonatal diabetes (Gloyn AL et al., N Engl Med 350;18:20-31, 2004). So far several different Kir6.2 mutations have been reported which explain about 30-50% of the etiology of PNDM in different populations. The diagnosis of this disease is important because sulfonylurea treatment is effective in these patients, and insulin therapy can be stopped. Homozygous inactivating mutations in the glucokinase (GCK) gene explain a minor proportion of cases of PNDM (Njølstad PR et al. N Engl J Med, 344:1588-1592, 2001). Heterozygous mutations in GCK gene can cause MODY2, which can lead to hyperglycemia already at young age.

Genetic analysis of PNDM is recommended in situations where diabetes is diagnosed in a child whose age is < 6 months. It includes a sequencing of the coding regions of ABCC8 (SUR1), KCNJ11 (Kir6.2), GCK, INS and FOXP3 genes. If an infant is hyperglycemic or one of the parents of both have a diabetes, screening of the entire coding region of GCK gene is recommended.

The analysis is performed from a whole blood sample (EDTA). Instructions for storage and sending the sample as well as prices for DNA screening are given in the request form. The report and interpretation of the results are mailed to the address given in the order approximately four weeks after the arrival of the blood sample.

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