Diagnosis and treatment of neonatal diabetes: a United States experience

Abstract

Background/objective: Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50% of patients diagnosed with diabetes before 6 months of age and in a small fraction of those diagnosed between 6 and 12 months. The aim of this study was to identify the genetic cause of diabetes in 77 consecutive patients referred to the University of Chicago with diabetes diagnosed before 1 yr of age.

Methods: We used Oragene DNA Self-Collection kit to obtain a saliva sample for DNA. We sequenced the protein-coding regions of KCNJ11, ABCC8, and INS using standard methods.

Results: We enrolled 32 patients diagnosed with diabetes before 6 months of age and 45 patients diagnosed between 6 and 12 months. We identified a mutation in KCNJ11 in 14 patients from 12 families and in INS in 7 patients from 4 families. Three of the patients with an INS mutation were diagnosed with diabetes between 6 and 12 months of age. Finally, we found that two patients had an abnormality of chromosome 6q24 associated with transient neonatal diabetes mellitus.

Conclusions: We were able to establish a genetic cause of diabetes in 63% of patients diagnosed with diabetes before 6 months of age and in 7% of patients diagnosed between 6 and 12 months. Genetic testing, which is critical for guiding appropriate management, should be considered in patients diagnosed with diabetes before 1 yr of age, especially if they are autoantibody negative, although the presence of autoantibodies does not rule out a monogenic cause.

Fig. 1

Partial pedigrees of 12 families with neonatal diabetes mellitus because of a mutation in KCNJ11. Circles represent females and squares represent males. Black symbols represent individuals with diabetes. A slash through the symbol indicates that the family member is deceased. The genotype is indicated under the symbols. Amino acid change/N, one mutated and one normal allele; N/N, two normal alleles; NA, not available for testing. The arrow indicates the proband.

Fig. 2

Plasma glucose values by date for patient with transient neonatal diabetes mellitus (BP90) because of a methylation defect of 6q24. The patient was discharged from hospital at 6 wk of age without insulin supplement. The values were obtained from the patient’s mother who was told to monitor plasma glucose daily. This graph demonstrates the gradual normalization of glucose values as the patient enters remission. Red lines on the x-axis indicate days when the patient had a fever or other illness.