Permanent neonatal diabetes mellitus (PNDM) is a newly identified and potentially treatable form of monogenic

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

. This type of

neonatal diabetes Neonatal diabetes mellitus (NDM) is a disease that affects an infant and their body's ability to produce or use insulin. NDM is a monogenic (controlled by a single gene) form of diabetes that occurs in the first 6 months of life. Infants do not pr ...

is caused by activating mutations of the ''

KCNJ11 Kir6.2 is a major subunit of the ATP-sensitive K+ channel, a lipid-gated inward-rectifier potassium ion channel. The gene encoding the channel is called KCNJ11 and mutations in this gene are associated with congenital hyperinsulinism. Structur ...

'' gene, which codes for the Kir6.2 subunit of the beta cell K_ATP channel. This disease is considered to be a type of

maturity onset diabetes of the young Maturity-onset diabetes of the young (MODY) refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production. MODY is often referred to as monogenic diabetes to disting ...

(MODY).

Cause

It can be associated with '' GCK'', ''

'', ''

INS INS or Ins or ''variant'', may refer to: Places * Ins, Switzerland, a municipality * Creech Air Force Base (IATA airport code INS) * Indonesia, ITF and UNDP code INS Biology *'' Ins'', a New World genus of bee flies * INS, the gene for the insul ...

'', and ''

ABCC8 ATP-binding cassette transporter sub-family C member 8 is a protein that in humans is encoded by the ''ABCC8'' gene. ''ABCC8'' orthologs have been identified in all mammals for which complete genome data are available. The protein encoded by this ...

''.

Diagnosis

This results in congenital impairment of insulin release, although in the past, this was always being thought to be unusually early

type 1 diabetes mellitus Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...

. The insulin deficiency results in

intrauterine growth retardation Intrauterine growth restriction (IUGR), or fetal growth restriction, refers to poor growth of a fetus while in the womb during pregnancy. IUGR is defined by clinical features of malnutrition and evidence of reduced growth regardless of an infant's ...

with birth weight small for gestational age. The diabetes is usually diagnosed in the first 3 months of life due to continuing poor weight gain, polyuria, or

diabetic ketoacidosis Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion and occasionally loss of ...

. Rare cases have been recognized as late as 6 months of age.

Treatment

Remarkably, this type of diabetes often responds well to sulfonylureas and insulin may not be necessary. More severe mutations in the KCNJ11 gene can cause early-onset diabetes which does not respond to the sulfonylurea drugs, as well as a syndrome of developmental delay and neurological features called the DEND syndrome. These forms of diabetes are very rare conditions, appearing in about 1/100,000 to 1/200,000 live births, and accounting for about 1/1000 of type 1 diabetes cases. Fewer than 5% of the cases assumed to exist have been diagnosed, and most diabetes clinics around the world are checking for KCNJ11 mutations in any persons who developed apparent insulin-dependent diabetes without the typical type 1 antibodies before 6 months of age. At least some of these people have been able to change from insulin to

sulfonylurea Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...

pills after decades of injections.

References

External links

GeneReviews/NCBI/NIH/UW entry on Permanent Neonatal Diabetes Mellitus

DiabetesGenes - Information about diagnosis, testing and treatment of neonatal diabetes
{{Diabetes Diabetes Neonatology

Cause

Diagnosis

Treatment

See also

References

External links