J Korean Med Sci.  2017 Jun;32(6):1042-1045. 10.3346/jkms.2017.32.6.1042.

DEND Syndrome with Heterozygous KCNJ11 Mutation Successfully Treated with Sulfonylurea

• Cho JH
• Kang E
• Lee BH
• Kim GH
• Choi JH
• Yoo HW

• KMID: 2377737
• DOI: http://doi.org/10.3346/jkms.2017.32.6.1042

Abstract

Permanent neonatal diabetes mellitus (PNDM) is caused by mutations in the ATP-sensitive potassium channel (K(ATP) channel) subunits. Developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome is the most severe form of PNDM and is characterized by various neurologic features. We report on a patient with DEND syndrome following initial misdiagnosis with type 1 DM, who was successfully switched from insulin to sulfonylurea therapy. A 50-day-old male presented with fever and seizure, complicated by persistent hyperglycemia. Insulin therapy was initiated. At 10 months of age, the patient was unable to hold his head up and make eye contact with others. At 17.9 years of age, direct sequencing of KCNJ11 identified a heterozygous mutation of c.602G>A (p.R201H). Since then, treatment with gliclazide was initiated and the insulin dose was gradually reduced. Following 3 months, insulin was discontinued with a gliclazide dose of 2.4 mg/kg. The patient continued to have excellent glycemic control with a glycated hemoglobin (HbA1c) level of 5.8% after 5 months. However, the patient's psychomotor retardation did not improve. This study reports the first case of DEND syndrome in Korea caused by a KCNJ11 mutation and emphasizes the necessity to screen mutations in KATP channel genes in patients with neonatal diabetes.

Keyword

DEND Syndrome; KCNJ11; Neonatal Diabetes; Sulfonylurea

MeSH Terms

Diabetes Mellitus
Diagnostic Errors
Epilepsy
Fever
Gliclazide
Head
Hemoglobin A, Glycosylated
Humans
Hyperglycemia
Insulin
Korea
Male
Potassium Channels
Seizures
Gliclazide
Insulin
Potassium Channels

Figure

• 

  Fig. 1 MRI of the brain at 21 months of age. The brain MRI demonstrates symmetric high signal intensity of periventricular white matter on T2-weighted and FLAIR images, suggesting hypoxic anoxic encephalopathy or metabolic encephalopathy. Myelination and migration of the underlying brain is normal. No other structural abnormalities including ventricle dilatation or encephalomalatic change are detected. MRI = magnetic resonance imaging, FLAIR = fluid-attenuated inversion recovery.

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  Fig. 2 Direct sequencing of the KCNJ11 gene. Partial sequences of KCNJ11 demonstrate a heterozygous mutation of c.602G>A (p.R201H).

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  Fig. 3 The clinical course of the patient with DEND syndrome. The insulin dose was tapered over 3 months and successfully switched to sulfonylurea (2.4 mg/kg/day). Serum C-peptide was undetectable (< 0.5 ng/mL) prior to sulfonylurea therapy. At 18.7 years of age, HbA1c was found to be 5.8%, indicating a well-controlled status following the switch to sulfonylurea. DEND = developmental delay, epilepsy, and neonatal diabetes, HbA1c = glycated hemoglobin.

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