Precision medicine for a man presented with diabetes at 2-month old

A 22-year-old man was referred for continuation of diabetes mellitus treatment. He was first diagnosed with diabetes mellitus 2 months after birth, when he failed to thrive and showed symptoms of diabetic ketoacidosis. There was no family history of diabetes mellitus. The patient did not exhibit the...

Full description

Saved in:
Bibliographic Details
Published in:European journal of human genetics : EJHG 2019-06, Vol.27 (6), p.989-993
Main Authors: Ang, Su Fen, Tan, Clara Si Hua, Fong, Jessie Choi Wan, Lim, Su Chi
Format: Article
Language:English
Subjects:
Adult
Amino Acid Substitution
Brief Communication
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - therapy
Diabetic ketoacidosis
Diagnosis
Epilepsy
Genetic screening
Glibenclamide
Health risk assessment
Humans
Hypertrophy
Hypoglycemia
Infant
Insulin
KCNJ11 gene
Ketoacidosis
Male
Mutation, Missense
Neonates
Potassium channels (inwardly-rectifying)
Potassium Channels, Inwardly Rectifying - genetics
Precision Medicine
Titration
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A 22-year-old man was referred for continuation of diabetes mellitus treatment. He was first diagnosed with diabetes mellitus 2 months after birth, when he failed to thrive and showed symptoms of diabetic ketoacidosis. There was no family history of diabetes mellitus. The patient did not exhibit the full set of features to be qualified for any developmental delay, epilepsy and neonatal diabetes mellitus (DEND) syndrome. Insulin replacement therapy was initiated; however, management was challenged by wide glycemic excursion, hypoglycemic unawareness and insulin-associated cutaneous lipo-hypertrophy. Re-evaluation, including genetic testing, revealed a heterozygous missense p.Arg201Cys variation in the KCNJ11 gene encoding the potassium channel subunit Kir6.2. Successful treatment conversion from insulin to glibenclamide was achieved over an extended period of 2 months (up-titrating to a dose of 1.0 mg/kg) in this patient despite his long diabetes duration of 27 years with elimination of hypoglycemia unawareness and achievement of excellent glycemic control sustained over more than 5 years. This case highlights the importance of after having secured a firm genetic diagnosis, to undertake conversion to sulphonylurea with careful dose titration and perseverance over months. Confirmation of variants with functional implications by genetic testing in patients suspected of neonatal diabetes is important for accurate molecular diagnosis and precision-treatment strategy with optimal outcome.
ISSN:1018-4813
1476-5438
DOI:10.1038/s41431-019-0371-z