Published in:
01-01-2017 | Scientific Letter
Genetically Confirmed Neonatal Diabetes: A Single Centre Experience
Published in: Indian Journal of Pediatrics | Issue 1/2017
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To the Editor: Neonatal diabetes mellitus (NDM) is a rare form of monogenic disorder with onset usually within 6 mo of age [1]. Mutations in the potassium channel subunits encoding genes viz. KCNJ11 and ABCC8 among the 23 reported till recently (6q24, ABCC8, EIF2AK3, FOXP3, GATA4, GATA6, GCK, GLIS3, HNF1B, IER3IP1, INS, KCNJ11, MNX1, NEUROD1, NEUROG3, NKX2–2, PDX1, PTF1A, RFX6, SLC19A2, SLC2A2, STAT3 and ZFP57), the two commonly involved genes in NDM, have important therapeutic implications as sulfonylurea therapy might be effective in such patients [1, 2]. We describe the spectrum of genotypic and phenotypic characteristics of NDM patients referred to a single tertiary care centre (Table 1).
Table 1
Genotype and phenotype of NDM patients
|
Diagnosis
|
Age of onset (mo)
|
Presentation & associated features
|
Mutation identified
|
Before SU trial
|
After SU trial
|
Current treatment & glycemic control (last HbA1C)
|
|||
|---|---|---|---|---|---|---|---|---|---|
|
HbA1C (%)
|
C peptide (ng/ml)
|
HbA1C (%)
|
C peptide (ng/ml)
|
||||||
|
Case 1: Male
|
PNDM
|
2
|
DKA
|
E382V– Novel homozygous missense mutation in exon 7 of ABCC8 gene.
|
9
|
0.4
|
7.4
|
3.8
|
• On glibenclamide (0.07 mg/kg/d)
• HbA1c 5.9 %
|
|
Case 2: Female
|
PNDM
|
112
|
Osmotic symptoms with LRTI
|
E382V– Novel homozygous missense mutation in exon7 of ABCC8 gene.
|
8.2
|
0.2
|
6.8
|
3.5
|
• On glibenclamide (0.17 mg/kg/d)
• HbA1c 6.7 %
|
|
Case 3: Female
|
PNDM
|
2
|
• DKA
• Dysmorphic features & later delayed milestones
|
F1164 L– Novel homozygous missense mutation in exon 28 of ABCC8 gene
|
14.8
|
<0.1
|
Not available
|
• On glibenclamide (0.5 mg/kg/d)
• HbA1c 7.1 %
|
|
|
Case 4: Male
|
PNDM
|
9
|
DKA
|
p.R89c – Heterozygous missense mutation in exon 3 of INS gene
|
SU trial not applicable
|
• On insulin (0.5 IU/kg/d)
• HbA1c 9.0 %
|
|||
|
Case 5: Male
|
WRS
|
3
|
• DKA
• Later developed Developmental delay, Short stature, Dysmorphic features, Skeletal Spondyloepiphysiometaphyseal dysplasia, Exocrine pancreatic insufficiency, Chronic liver disease. (Had normal thyroid functions and no thyroid autoimmunity)
|
p.R1064x – Homozygous nonsense mutation in exon 17 of EIF2AK3 gene
|
SU trial not applicable
|
• On insulin (1.25 IU/kg/d) + pancreatic enzyme supplements + supportive management
• HbA1C- 10.3 %
|
|||
|
Case 6: Male
|
TNDM
|
1
|
DKA
|
G832D – Novel heterozygous missense mutation in exon 21 of ABCC8 gene
|
SU trial not given, was managed by insulin
|
Remission at 6 mo
|
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