Permanent neonatal diabetes by a new mutation in KCNJ11: unsuccessful switch to sulfonylurea.
Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (KATP). Sulfonylureas promote KATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene - KCNJ11:c1001G>7 (p.Gly334Val) - and confirmed the diagnosis of PNDM. Therefore it was attempted to switch from insulin therapy to sulfonylurea. During glibenclamide institution C-peptide levels increased, however the suboptimal glycemic control lead us to restart an intensive insulin scheme. This new variant of KCNJ11 mutation had a phenotypic lack of response to sulfonylurea therapy. Age, prior poor metabolic control and functional change of KATP channel induced by this specific mutation may explain the observed unsuccessful switch to sulfonylurea. Interestingly, C-peptide levels raise during glibenclamide administration support some degree of improvement in insulin secretory capacity induced by the treatment. Understanding the response to sulfonylurea is crucial as successful treatment may be life-changing in these patients.
Instituto de Investigação e Inovação em Saúde, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Eva
E
Lau
Departamento de Pediatria, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Cintia
C
Correia
Instituto de Investigação e Inovação em Saúde, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Paula
P
Freitas
Departamento de Endocrinologia, Diabetes e Metabolismo, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Claúdia
C
Nogueira
Departamento de Endocrinologia, Diabetes e Metabolismo, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Maria
M
Costa
Departamento de Endocrinologia, Diabetes e Metabolismo, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Ana
A
Saavedra
Departamento de Pediatria, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Carla
C
Costa
Instituto de Investigação e Inovação em Saúde, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Davide
D
Carvalho
Departamento de Pediatria, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Manuel
M
Fontoura
D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000235:genetics*; D057915:Drug Substitution; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D017211:Treatment Failure; D055815:Young Adult; D000099161:Kcnj11 Channel
D001786:Blood Glucose; D002096:C-Peptide; D005905:Glyburide; D007004:Hypoglycemic Agents; D024661:Potassium Channels, Inwardly Rectifying; D013453:Sulfonylurea Compounds; D000099161:Kcnj11 Channel