Endocrine Abstracts

JOINT3285

Introduction: Cornelia de Lange syndrome (CdLS) is a rare genetic disorder characterized by growth and developmental delay, typical dysmorphic features, and genitourinary system anomalies. Diabetes mellitus (DM) has been rarely reported in CdLS, and its etiology remains unclear.

Case: A 4-year-old male presented with respiratory distress following a one-week history of fever, cough, vomiting, and fatigue. He was born at 32 weeks of gestation (BW 935 g) via cesarean section due to fetal distress. He remained in the neonatal intensive care unit for 4 months. Dysmorphic features (microcephaly, synophrys, hypoplastic external genitalia) led to a diagnosis of CdLS (NIPBL exon 37, c.6461T>C heterozygous mutation). He required gastrostomy at 4.5 months, developed epilepsy at 1 year, and a cochlear implant was placed for bilateral hearing loss at 14 months. On admission, the patient was lethargic, hypotensive, and tachypneic with dehydration. Height was 82 cm (-5.1SDS), and weight 9.8 kg (-5.7SDS). Laboratory revealed a blood glucose of 1693 mg/dL, sodium 162mEq/l, potassium 4.42mEq/l, creatinine 1.8mg/dL, BUN 79mg/dL, pH 7.28, HCO₃ 19 mmol/l, negative urine ketones. He was diagnosed with nonketotic hyperosmolar state. A bolus of isotonic saline (20 mL/kg) was followed by 5% dextrose and 0.45% saline infusion at a rate of 4 L/m²/day. Regular insulin infusion (0.025 U/kg/h) was initiated two hours after hydration. Persistent respiratory distress and hypotension required intubation and adrenaline infusion. Blood glucose gradually decreased, ketones remained negative. After 17 hours, the metabolic and clinical condition improved, insulin infusion was discontinued. However, hypernatremia persisted for 78 hours, necessitating free water supplementation. Pulmonary edema developed during this period, leading to a reduction in fluid intake. Further evaluation during hyperglycemia revealed low C-peptide (0.466ng/mL) and insulin (2.97mIU/l), an HbA1c of 9.3%, positive anti-GAD antibodies (15U/l). Basal insulin (0.4 U/kg/day) in two doses along with correction boluses was started. During follow-up, insulin was temporarily discontinued. However, hyperglycemia recurred five months later, requiring the re-initiation of basal insulin therapy (0.58 U/kg/day).

Conclusion: Diabetes has been rarely reported in CdLS, and this case represents the first well-documented pediatric Type 1 DM. Hyperosmolar state is an uncommon presentation of Type 1 DM in children. The syndromic condition may have contributed to the atypical clinical course of diabetes in this patient.

Keywords: Cornelia de Lange syndrome, Type 1 Diabetes Mellitus, Nonketotic Hyperosmolar State