7884 Enigmatic Spontaneous Hypoglycemia During Prolonged Complete Remission in a Child with Autoantibody-Positive Diabetes: Possible Role of Coincidental GYS2 Heterozygous Mutation

Abstract Disclosure: S.S. Sundar: None. S. Shankar: None. M.S. Vaishnav: None. L. Lekkala: None. S.S. Srikanta: None. R.B. V: None. T.-. Kamala: None. C. Siddlingappa: None. C.D. Mandyam: None. P. Ravikumar: None. K. M: None. V. Nath: None. Introduction: Complete remission duration in type 1 diabetes is highly variable (few weeks to years, average 7 months in children). Non-diabetes hypoglycemia in children occurs due to metabolic/ endocrine/ congenital disorders [insulin-mediated (hyperinsulinism) or insulin-independent]. Clinical Case 2021 Sep T1D Diagnosis 13-year boy FTLSCS; 2.86 kg. Fatigue, sleepy, early morning headaches, weight loss, polyuria, polydipsia, headache. FPG 320 mg/dL; PPPG 596 mg/dL; Ketonuria++++; C Peptide fasting 0.42 ng/ml (1.1-4.4); TSH 2.44 (0.7-6.4); S Cortisol 27.2 mcg/dL (5-23); US abdomen normal. Treatment: IV fluids/ insulin; Regular 10 u tid; Glargine 20 u Family history: Diabetes adult onset++++; Hypothyroidism++ 2021 Oct T1D remission Hypoglycemia even with Glargine 2 U/day. Insulin discontinued. FPG 88; PPBG 159 2021 Dec Endocrinology work-up Weight 41.9 kg; Height 154 cm BMI 18.0 kg/m2 FPG 88; HbA1c 6.1 % (4.8-5.6); C-peptide fasting 1.26; Blood ketone 3.35 (0.2-2.8); TSH 2.66 Autoantibodies Islet cell IFL Positive; IA2 >280 IU/mL (<28); GAD65 0.5 U/mL (<10); TPO negative 2021-2023 T1D prolonged remission FPG 90; PPBG 140; HbA1c 5.5 2023 Nov 5 Hypoglycemia, coma and seizures Limited breakfast; skipped lunch; vomiting. 1.15 am: Unconscious seizures. CGM unable to record. Lab BG 39; Fingerstick BG 36. IV dextrose 25%. 4 am: Regained consciousness. BG 100 to 200; HbA1c 6.4%. Insulin fasting 8.9 µU/ml (2.6-24.9); Insulin post prandial 21.6; C Peptide fasting 2.0. S Cortisol 8 am 7.6. Imaging: MRI brain abdomen pelvis normal. EEG normal 2023 Nov 9 Hyperglycemia to hypoglycemia Holiday morning: BG unexpected 306 CGM. 8.30 pm: Symptomatic hypoglycemia with sweating and light headedness; BG 52 fingerstick. IV 25% dextrose. BG 140 “Coincidental” spontaneous hypoglycemia No intake of insulin/ oral hypoglycaemics / traditional medicines. 10 pm to 3 am low CGM BG upto 60; asymptomatic. FPG 103; PPPG 146; HbA1c 6.3 %; Insulin Fasting 2.85, 3.79; C-peptide fasting 1.18, 0.94; S Cortisol 8 am 12.5; TSH 2.66 Autoantibodies Islet cell IFL Positive; IA2 >280 IU/mL (<28); GAD65 0.5 U/mL (<10); ZnT8 50 AU/mL (<10); Insulin antibodies 3.7 (<10). TPO negative Whole genome sequencing No monogenic/ maturity onset/ mitochondrial diabetes mutations. Hepatic glycogen synthase 2 heterozygous mutation (c.1602+1G-T) detected (Glycogen Storage Disease Type 0 Autosomal recessive: Ketotic hypoglycemia after prolonged fasting and postprandial hyperglycemia and hyperlactatemia in infancy or early childhood). Clinical Lessons Coincidental double metabolic glucose dyshomeostasis pathology? Susceptibility of heterozygous carriers of GYS2 mutations to glucose metabolism abnormalities (hypoglycemia and hyperglycemia) has been reported. Presentation: 6/2/2024