Permanent Neonatal Diabetes Mellitus: Same Mutation, Different Glycemic Control with Sulfonylurea Therapy on Long-Term Follow-up

Abstract Objective. Mutations of the KCNJ11 gene are the most common cause of the permanent neonatal diabetes mellitus (PNDM). Majority of people with KNCJ11-PNDM have a de-novo mutation. We aimed to compare diabetes phenotype in two children and their mothers with PNDM carrying the same sulfonylurea-sensitive KCNJ11 variants. Methods. We have compared glibenclamide (sulfonylurea) dose, C-peptide, and HbA1c serum levels in two children and their mothers with PNDM up to 5.5-year follow-up. All of them were carrying a heterozygous activating KCNJ11 pathogenic variant (p.R201H in Family 1 or p.H46Y in Family 2). The mothers were initially treated with insulin and successfully switched to sulfonylurea at the age of 24 and 11 years, respectively. Both children were treated with sulfonylurea since the diagnosis of PNDM. Results. Glibenclamide dose was similar in both children (0.02–0.03 mg/kg/day), but lower compared to their mothers (0.1–0.4 mg/kg/day) (p<0.002). Fasting serum C-peptide levels were also lower in children (70–210 pmol/l) than in their mothers (263–720 pmol/l) (p<0.002), but no significant differences were observed in postprandial C-peptide levels. HbA1c was lower only in the son of SVK4 (Family 2) compared to his mother, as she had poor adherence to the sulfonylurea therapy during the first years after the sulfonylurea switch. Conclusions. Evaluation of the treatment in people with sulfonylurea-sensitive KNCJ11-PNDM should respect the age of patients together with the type of mutation and duration of diabetes at therapy start and may differ within one family.

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Long-term follow-up of a child with Wolcott-Rallison syndrome

BMJ Case Reports ◽

10.1136/bcr-2021-242376 ◽

2021 ◽

Vol 14 (5) ◽

pp. e242376

Author(s):

Nikhil Shah ◽

Madhura Bharat Karguppikar ◽

Vaman Khadilkar ◽

Anuradha Khadilkar

Keyword(s):

Diabetes Mellitus ◽

South Asia ◽

Poor Prognosis ◽

Neonatal Diabetes ◽

Permanent Neonatal Diabetes ◽

Common Cause ◽

Long Term Follow Up ◽

Basal Bolus

Wolcott-Rallison syndrome (WRS), the most common cause of permanent neonatal diabetes mellitus (DM) in consanguineous families, has a poor prognosis, with a mean survival of 5.8 years. Majority of children with WRS succumb to the disease in the first decade of life. We present the long-term follow-up of an 8-year-2-month-old girl with genetically proven WRS who was born to a non-consanguineous parentage. She is on basal bolus regimen of insulin therapy for DM. In addition, she was noted to have features of skeletal dysplasia at 3 years and 3 months of age, which has led to her short stature. Surprisingly, she has had no episodes of hepatitis or liver dysfunction so far, which is frequently seen in children with WRS. To the best of our knowledge, she is the oldest surviving patient with WRS reported in India and South Asia.

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