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Interdisciplinary CompetenceMolecular Diagnostics
Know how in the analysis of genetic material.
For the benefit of patients.

IllnessDiabetes mellitus, neonatal; differential diagnosis


Short information

Comprehensive differential diagnostic panel for Aicardi-Goutières syndrome cotaining 24 guideline-curated core genes and altogether 40 curated genes according to the clinical signs

Number of genes
26 Accredited laboratory test
Examined sequence length
37,1 kb (Core-/Core-canditate-Genes)
40,6 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications




Gene panel

Selected genes

NameExon Length (bp)OMIM-GReferenz-Seq.Heredity
ABCC84746NM_000352.6AD, AR
GCK1398NM_000162.5AD, AR
INS333NM_000207.3AD, AR
ZFP571611NM_001109809.5AD, AR

Informations about the disease

Clinical Comment

Neonatal diabetes mellitus occurs in two different forms, permanent or transient. Permanent neonatal diabetes mellitus begins in the first six months of life and persists throughout life due to insulin deficiency. In these patients, intrauterine growth retardation occurs, and the infants suffer from dehydration and failure to thrive. In some cases, developmental delay and epilepsy are observed, and a few have pancreatic malformations. One third of these patients have mutations in the KCNJ11 gene, and 20% each show mutations in the ABCC8 or INS genes. If the disorder is caused by mutations in the KCNJ11 or INS genes, autosomal dominant inheritance is present. However, in 90% of cases, the disease arises from new mutations in these genes. When diabetes is caused by mutations in the ABCC8 gene, it can be either autosomal dominantl or recessively inherited. Less commonly, the disease is caused by mutations in other genes with autosomal recessive inheritance.

6q24-related transient neonatal diabetes mellitus is a form that occurs in infants, and it is also characterised by insulin deficiency hyperglycaemia. These patients suffer from severe intrauterine growth retardation, and the infants are usually dehydrated by the first week of life. Symptoms subside over time and generally disappear by 3-18 months of age. However, diabetes can recur, especially during childhood illness or during pregnancy, thus up to 50% of those affected will still develop permanent diabetes later in life. Other features of 6q24-related diabetes include macroglossia, umbilical hernias, brain, heart or kidney malformations, muscle hypotonia, deafness and developmental delay. This form of diabetes is caused by overexpression of genes in the affected chromosomal region due to disturbed genomic imprinting - including of the PLAGL1 gene. About 40% of cases are caused by paternal uniparental disomy, another 40% by paternal duplications and the remaining 20% by maternal hypomethylation, half of which are caused by mutations in the ZFP57 gene. Thus, most cases of 6q24-related transient neonatal diabetes are not inherited, yet ZFP57 mutations cause an autosomal recessive pattern. Since the overall DNA diagnostic yield is 80% together in permanent and transient neonatal diabetes, a negative molecular genetic result does not exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1447/



  • Alias: Neonatal diabetes mellitus (NDM)
  • Allelic: Cataract 41 (WFS1)
  • Allelic: Deafness, AD 6/14/38 (WFS1)
  • Allelic: Diabetes mellitus, gestational (GCK)
  • Allelic: Diabetes mellitus, insulin-dependent (HNF1A)
  • Allelic: Diabetes mellitus, insulin-dependent, 2 (INS)
  • Allelic: Diabetes mellitus, insulin-dependent, 20 (HNF1A)
  • Allelic: Diabetes mellitus, noninsulin-dependent (ABCC8, HNF1B, HNF4A, SLC2A2)
  • Allelic: Diabetes mellitus, noninsulin-dependent, 2 (HNF1A)
  • Allelic: Diabetes mellitus, noninsulin-dependent, association with (WFS1)
  • Allelic: Diabetes mellitus, noninsulin-dependent, late onset (GCK)
  • Allelic: Diabetes mellitus, type 1 (INS)
  • Allelic: Diabetes mellitus, type 2, susceptibility to (KCNJ11)
  • Allelic: Diabetes mellitus, type II, susceptibility to (PDX1)
  • Allelic: Diarrhea 4, malabsorptive, congenital (NEUROG3)
  • Allelic: Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young (HNF4A)
  • Allelic: Hepatic adenoma, somatic (HNF1A)
  • Allelic: Hyper-IgE recurrent infection syndrome (STAT3)
  • Allelic: Hyperinsulinemic hypoglycemia, familial, 1 (ABCC8)
  • Allelic: Hyperinsulinemic hypoglycemia, familial, 2 (KCNJ11)
  • Allelic: Hyperinsulinemic hypoglycemia, familial, 3 (GCK)
  • Allelic: Hypoglycemia of infancy, leucine-sensitive (ABCC8)
  • Allelic: MODY, type II (GCK)
  • Allelic: MODY, type III (HNF1A)
  • Allelic: MODY, type IV (PDX1)
  • Allelic: MODY, type VI (NEUROD1)
  • Allelic: MODY, type X (INS)
  • Allelic: Neuropathy, distal hereditary motor, type VC (BSCL2)
  • Allelic: Silver spastic paraplegia syndrome (BSCL2)
  • Allelic: Thiamine-responsive megaloblastic anemia syndrome (SLC19A2)
  • Allelic: Vissers-Bodmer syndrome (CNOT1)
  • Allelic:MODY, type I (HNF4A)
  • Asphyxiating thoracic dystrophy syndrome + infantile‐onset diabetes [panelapp] (PDIA6)
  • Autoimmune disease, multisystem, infantile-onset, 1 (STAT3)
  • Congenital generalised lipodystrophy, severe insulin resistance + diabetes [panelapp] (BSCL2)
  • Currarino syndrome (MNX1)
  • Diabetes mellitus, neonatal, with congenital hypothyroidism (GLIS3)
  • Diabetes mellitus, permanent neonatal (ABCC8, GCK, INS)
  • Diabetes mellitus, permanent neonatal, with neurologic features (KCNJ11)
  • Diabetes mellitus, transient neonatal (KCNJ11)
  • Diabetes mellitus, transient neonatal 2 (ABCC8)
  • Diabetes, mellitus, insulin-dependent, susceptibility to, 10 (IL2RA)
  • Diabetes, permanent neonatal (KCNJ11)
  • Encephalopathy, progressive, with/-out lipodystrophy (BSCL2)
  • Fanconi-Bickel syndrome (SLC2A2)
  • Holoprosencephaly 12, with or without pancreatic agenesis (CNOT1)
  • Immunodeficiency 41 with lymphoproliferation + autoimmunity (IL2RA)
  • Immunodysregulation, polyendocrinopathy, enteropathy, XL, IPEX (FOXP3)
  • Leukoencephalopathy with vanishing white matter 1, +/- ovarian failure (EIF2B1)
  • Lipodystrophy, congenital generalized, type 1 (AGPAT2)
  • Lipodystrophy, congenital generalized, type 2 (BSCL2)
  • MEHMO [Mental retard., Epilepsy, Hypogonadism/-genitalism, Microcephaly, Obesity] syndrome (EIF2S3)
  • Microcephaly, epilepsy + diabetes syndrome (IER3IP1)
  • Microcephaly, epilepsy + diabetes syndrome 2 (YIPF5)
  • Mitchell-Riley syndrome, includes neonatal diabetes (RFX6)
  • Neonatal diabetes + generalised lipodystrophy [panelapp] (BSCL2)
  • Neonatal diabetes mellitus [MONDO:0016391, panelapp] (ONECUT1)
  • Neonatal diabetes mellitus [MONDO:0016391, panelapp] (ZNF808)
  • Neonatal diabetes mellitus [MONDO:0016391] (IL2RA)
  • Neonatal diabetes, pancreatic agenesis and/or congenital heart defects (GATA4)
  • ONECUT1-associated neonatal diabetes [panelapp] (ONECUT1)
  • Pancreatic agenesis 1 (PDX1, PTF1A)
  • Pancreatic agenesis [MONDO:0009832, panelapp] (ZNF808)
  • Pancreatic agenesis and congenital heart defects (GATA6)
  • Renal cell carcinoma (HNF1A, HNF1B)
  • Renal cysts and diabetes syndrome (HNF1B)
  • Wolcott-Rallison syndrome (EIF2AK3)
  • Wolfram syndrome 1 (WFS1)
  • Wolfram-like syndrome, AD (WFS1)
Heredity, heredity patterns etc.
  • AD
  • AR
  • Meth
  • XLR
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatics and clinical interpretation

No text defined