Diabetes mellitus: congenital neonatal
Prevalence is estimated at 1/400,000 newborns.
- 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 .
- 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)
- 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
close monitoring of glycemia
- Polak M, Busiah K, Cavé H.
Diabète néonatal : maladie de l’empreinte 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