Neonatal diabetes mellitus (NDM) is a disease that affects an infant and their body's ability to produce or use insulin.

Those with transient neonatal diabetes tend to have symptoms in the first few days or weeks of life, with affected children showing weight loss and signs of dehydration, along with high levels of sugar in the blood and urine.

[6] Neonatal diabetes is classified into three subtypes: permanent, transient, and syndromic; each with distinct genetic causes and symptoms.

[7] Despite the return of euglycemia, people with 6q24 overexpression are at high risk of developing diabetes later in life, as teenagers or adults.

[7] Many of the genetic variations that cause neonatal diabetes are inherited in an autosomal dominant manner, i.e. receiving a single copy of the disease-associated variant results in disease.

This is the case for the KATP genes KCNJ11 and ABCC8, and paternally inherited 6q24 amplifications, any of which have a 50% chance of being transmitted to each offspring of an affected individual.

Known genetic variants cause neonatal diabetes by five major mechanisms: Preventing the development of the pancreas or β cells, promoting β-cell death by autoimmunity or endoplasmic reticulum stress, preventing β cells from recognizing glucose or secreting insulin, or abnormal expression of the 6q24 region on chromosome 6.

[7] Disease-associated variants of either subunit of KATP, KCNJ11 and ABCC8, can result in a channel that is "stuck open", rendering the β cell unable to secrete insulin in response to high blood glucose.

[7] Children born with disease-associated KATP variants often have intrauterine growth restriction and resulting low birthweight.

Alternatively, inheriting a maternal copy of 6q24 with defective DNA methylation can result in similar over-expression of the locus.

[7][9] Similarly, variations in the transcription factors GLIS3, NEUROD1, NEUROG3, NKX2-2, or MNX1 can result in malformed or absent β cells that do not secrete insulin.

[10] EIF2AK3 variants can exacerbate ER stress causing β-cell death, skeletal issues, and liver dysfunction.

[7] Some variations in immune gene FOXP3 can cause IPEX syndrome, a severe and multifaceted disease that includes neonatal diabetes among its symptoms.

The previously listed genetic mechanisms result in twice the normal amount of these two genes and cause chromosome 6q24 TNDM.

[11] Other contributing factors are umbilical hernia and enlarged tongue, which are present in 9 and 30% of patients with chromosome 6q24 related TNDM.

In addition, molecular analysis of chromosomes 6 defects, KCNJ11 and ABCC8 genes (encoding Kir6.2 and SUR1) provide a way to identify PNDM in the infant stages.

Approximately 50% of PNDM are associated with the potassium channel defects which are essential consequences when changing patients from insulin therapy to sulfonylureas.

Microsatellites markers and polymerase chain reaction are used on the chromosomes of interest to test the DNA of the parent and child to identify the presence of uniparental disomy[14].

The most common mutations underlying neonatal diabetes – KCNJ11 and ABCC8 variants – can be treated with sulfonylureas alone, eventually transitioning off of insulin completely.