P-218: Intermittent diabetes mellitus and hyperinsulinemic hypoglycemia in the patient with de novo KMT2D gene mutation and multiple other endocrine disorders and congenital abnormalities
K Kotlyarevska, N Kotlyarevska, S BoydAbstract
Introduction
Patients with KMT2D mutations can develop neonatal hyperinsulinemic hypoglycemia, and diabetes mellitus as well as other endocrine disorders hypoparathyroidism, hypothyroidism, growth hormone deficiency. Growth hormone treatment can trigger hyperglycemia.
Objectives
To describe a rare case of patient with de novo KMT2D gene mutation, multiple endocrine disorders including transient neonatal diabetes, hyperinsulinemic hypoglycemia, hypothyroidism, hypoparathyroidism, GH deficiency. DM returned with GH use.
Methods
Newborn at 37 weeks of gestation, IUGR, developed hyperglycemia after dexamethasone use. Blood glucose 600 mg/dl, received insulin, that was weaned. At 1 month developed intermittent hypoglycemia, started diazoxide, stopped at 3 months. Abdominal MRI showed only pancreatic head present. Developed hypoparathyroidism, calcium 6.4 mg/dl, started calcium carbonate, calcitriol. Brain MRI showed pituitary cyst. Developed hypothyroidism: TSH=8.2 UIU/ml, fT4=0.9 ng/dl, started levothyroxine. Other issues: choanal atresia, sensorineural hearing loss, hypoplastic kidneys, athelia. Chromosomal microarray normal. MODY panel normal. Other genetic testing showed de novo mutation in KMT2D gene c.10721 T>A p.13574N. At 4 years of age height was plotting at -3.26 SD. Failed GH stim test, started on GH therapy, improved growth velocity 10.6 cm/year. 6 months into GH therapy - hyperglycemia, HbA1C 8.7%, required insulin. GH therapy stopped. Antibodies for DM I negative. Hyperglycemia improved but not resolved.
Results
This is a rare case report of patient with de novo KMT2D gene mutation, multiple other endocrine disorders, developed intermittent DM on several occasions – in neonatal period with dexamethasone use and with GH use.
Conclusions
KMT2D gene mutation is a rare disorder associated with multiple endocrine disorders including diabetes mellitus that can develop at different times of life. Treatment of other endocrine deficiencies such as GH deficiency brings a challenge in management of hyperglycemia.