Neonatal
Diabetes Mellitus.

Usually abbreviated to NDM.

There are two types, Permanent Neonatal Diabetes mellitus (PNDM) and Transient Neonatal Diabetes Mellitus (TNDM).

These types of diabetes are diagnosed in the first few months of a baby's life, fortunately in only around 1 of every 400,000 births. Like all forms of diabetes the levels of glucose in the blood goes too high, in this case because the pancreas fails to produce sufficient insulin. They are very rare form of the disease and not much is known about them. What is accepted is that they are not autoimmune diseases.

Symptoms include lethargy, dehydration, and breathing difficulties along with high levels of glucose in the blood and urine. Often, though not always, infants have a low birth weight.

It is not possible to tell the difference between the two types at initial diagnosis without complicated genetic testing - so it is just a case of wait and see.

Transient neonatal diabetes mellitus.
TNDM is, as it's name suggests, not permanent. It develops within days and can disappear in weeks or months. Usually insulin need only be given for around the first 3 months of life. There is the chance that Type 2 diabetes may reoccur during adolescence.

What causes TNDM is not yet known. It has been suggested that it is simply that the infant has immature beta-cells. Some studies have shown abnormalities of chromosome 6 in infants with TNDM which may be responsible for slowing down the maturation of the beta-cells. However that does not show up in all cases.

Permanent neonatal diabetes mellitus.
PNDM can also develop within days, but may take months and remains for life. Therefore if the diabetes persists beyond the first year it will be PNDM.

When these infants are tested for c-peptide levels they are non-existent, which indicates total failure of the beta-cells. It is very possible that the destruction occurred in utero.

Like MODY, PNDM is caused by a mutation in a gene, and not always the same gene.

Around half the cases have a mutation in the gene KCNJ11. This form of PNDM tends to develop later than other forms and can also be responsible for such complications as epilepsy or delayed motor development.

It does respond well to treatment by sulfonylurea drugs, which means there is still some form of pancreatic activity.

If the gene involved is the transcription factor insulin promoter factor (IPF)-1 or GCK there may be no beta-cell activity at all and insulin replacement therapy will be necessary.

In 2004 scientists from the Institute of Cancer Research in Sutton, UK found yet another gene that was responsible for PNDM in two UK families - PTF1A.
See affymetrix.com for details.

Genetic testing.
This can identify PNDM versus TNDM in new-borns and also identify which gene is responsible for the PNDM, which may help the doctor to choice the most appropriate therapy.

However, it is very expensive and considering the extreme rarity of this disease and the fact that the treatment is going to be given on the displayed symptoms, i.e. high blood sugar, anyway it is only for research purposes that it is ever done.

Hopefully enough will be known one day to make it worth while to screen all suspected carriers of the disease, so that if they have the gene they can make an informed decision as to whether to have children or not. Also the time may come when prenatal tests would show up the gene mutation in the foetus and it might be possible to treat it in utero.


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