Diabetes mellitus: congenital neonatal

Prevalence is estimated at 1/400,000 newborns. 

Two subtypes:

-         transient neonatal diabetes: very early onset (first days) with significant hyperglycemia, often without ketoacidosis; insulin needs are low and gradually decrease but the reappearance of diabetes in childhood or adolescence is frequent. The majority of the cases is due to an abnormality in chromosome 6

-         final or permanent neonatal diabetes [MIM 606 176]: less frequent than the transient form, it is generally associated with a mutation or a syndrome; 30-50% of cases are due to a mutation of the gene coding for the potassium channel in the ß cell .

Genetic aspects: 

-         PLAGL1 or HYMAI gene (6q24): usually, only the paternal allele is expressed. Diabetes appears in case of  parental paternal disomy of chromosome 6 (41%), of duplication (6q24) of the paternal allele (29%) or hypomethylation of the maternal allele; presence of neonatal macroglossia, umbilical hernia.

-         KCNJ11 (potassium channel J11) and ABCC8 (ATP-binding cassette carrier - Cmember 8 subfamily) genes (11p15.1): autosomal dominant transmission: these mutations cause a defect of closure of the potassium channel Kir6.2 or SUR1 that allows discontinuation of insulin release. Sulfonylureas (tolbutamide) close this channel and allow discontinuation of insulin release

-         INS (insulin) (11p15.5) gene: mutation that causes a defect in the synthesis of insulin

-         GCK gene that codes for glucokinase (7p13) regulating the metabolism of glucose in the ß cell, and thus the amount of insulin released;  homozygous mutations (very rare) cause a complete deficiency while heterozygous mutations cause a mild intolerance to glucose and a MODY 2 (see this term)

-         agenesis or hypoplasia of the pancreas: IPF1A (10p12.2) [MIM 615 935], PDX1 (13q12.2) [MIM 260 370] or GATA6 (18q11.2) [MIM 601 656] genes

-         FOXP3 (forkhead homeobox P3) (Xp11.23) gene coding for scurfine: X-linked syndrome IPEX (acronym for Immune dysregulation Polyendocrinopathy, Enteropathy, X-linked) that combines exfoliative dermatitis, refractory diarrhea with villous atrophy, hemolytic anemia, thrombocytopenia, glomerulonephritis, and autoimmune thyroiditis. Presence of antibodies against  glutamic acid decarboxylase (GAD)

-         mitochondrial disease

-         Berardinelli-Seip syndrome: insulin resistance, see this term

-         Wolcott-Rallison syndrome (SLC19A2 gene): see this term

-         pancreatic hypoplasia with congenital heart disease [MIM 600 001]: GATA6 gene (18q11.2)

-         neonatal diabetes mellitus and cerebellar hypoplasia [MIM 609 069]: PTF1A gene (10p12.2)

   insulin secretion by  ß cell

Anesthetic implications: 

close monitoring of glycemia

References : 

-        Polak M, Busiah K, Cavé H.
Diabète néonatal : maladie de lempreinte génétique, mais pas seulement!
Métabolismes, Hormones, Diabètes et Nutrition ; 2006 ; X, 21-8.

-        Yafi M.
A case of neonatal diabetes: presentation, diagnosis and management.
Austin J Pediatr 2014; 1: 1004

-        Kamoun T, Chabchoub I, Ben Ameur S, Kmiha S et al.
Transient neonatal diabetes mellitus and activating mutation in the KCNJ11 gene in two siblings.
Arch Pédiatr 2017; 24: 453-6

Updated: May 2017