Diagnosis and treatment of neonatal diabetes: a United States experience.
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.
Støy
Julie
J
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Greeley
Siri Atma W
SA
Paz
Veronica P
VP
Ye
Honggang
H
Pastore
Ashley N
AN
Skowron
Kinga B
KB
Lipton
Rebecca B
RB
Cogen
Fran R
FR
Bell
Graeme I
GI
Philipson
Louis H
LH
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D048909:Diabetes Complications; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005905:Glyburide / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000235:genetics* / Q000627:therapeutic use; D007859:Learning Disabilities / Q000209:etiology; D008297:Male; D010375:Pedigree; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D014481:United States / Q000453:epidemiology; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D005905:Glyburide; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel