Islet-Specific Antibody Seroconversion in Patients With Long Duration of Permanent Neonatal Diabetes Caused by Mutations in the KCNJ11 Gene
- Agnieszka Gach, MD1,
- Krystyna Wyka, PHD1,
- Maciej T. Malecki, MD, PHD2,
- Anna Noczynska, MD, PHD3,
- Jan Skupien, MD2,
- Joanna Nazim, MD, PHD4,
- Mieczyslaw Szalecki, MD, PHD5,
- Jerzy Bodalski, MD, PHD1,
- Jacek Sieradzki, MD, PHD2 and
- Wojciech Mlynarski, MD, PHD1
- 1Department of Pediatrics, Medical University of Lodz, Lodz, Poland
- 2Department of Metabolic Diseases, Jagiellonian University, Krakow, Poland
- 3Department of Endocrinology and Diabetology for Children and Adolescents, Medical University, Wroclaw, Poland
- 4Department of Pediatric Endocrinology, Polish-American Children Hospital, Krakow, Poland
- 5Diabetes Outpatient Clinic, Children's Hospital, Kielce, Poland
- Address correspondence and reprint requests to Wojciech Mlynarski, MD, PhD, Department of Pediatrics, Medical University of Lodz, 38/50 Sporna St., 91-738 Lodz, Poland. E-mail: wojciech.mlynarski{at}joslin.harvard.edu
Heterozygous activating mutations in the KCNJ11 gene are a common cause of permanent neonatal diabetes (PNDM) (1,2). In contrast to the autoimmune type 1 diabetes, patients with KCNJ11 mutations do not have serological markers of autoimmune β-cell destruction at disease onset (1,3–5). In such patients, hyperglycemia does not result from insulin-secreting cell destruction but rather from impaired insulin secretion. In addition, the majority of cases can be corrected with sulfonylurea therapy (2,6). Here, we report that carriers of the KCNJ11 mutation that are immunonegative at onset may show presence of islet antibodies in the further course of the disease.
RESEARCH DESIGN AND METHODS—
We sought to evaluate the clinical and genetic characteristics of patients with neonatal diabetes in Poland, using the Nationwide Registry, which was established in 2005 (7,8). Automatic sequencing of the KCNJ11 gene allowed identification of 15 patients with heterozygous mutations that cause neonatal diabetes. Sera from 11 carriers of the KCNJ11 gene mutation were available for the present study. None of the patients had a family history of type 1 diabetes. Informed consent was obtained from all subjects or their parents. The study was conducted in accordance with the Declaration of Helsinki (revised in 2000) and accepted by the local ethics committee in Lodz, Poland.
β-Cell antibody analysis
At diabetes onset.
Available data on …
