Is Spontaneous Hypoglycemia a Feature of XLID Type Nascimento?

Abstract

Introduction: X-linked intellectual disability (XLID) type Nascimento is a rare, under-diagnosed genetic disorder caused by intragenic mutations in the UBE2A gene. The syndrome was first described in 2006 by Nascimento et el. It is characterized by intellectual disability, dysmorphic facial features, skin anomalies, hypotonia, impaired speech, and seizures. To date, there is no literature to suggest that it affects glucose homeostasis.Case: A 63-year-old male with a history of XLID (mutation in UBE2A pL112P variant), seizures, dementia, stage II CKD, polycystic kidneys, and hyperkalemia presented to the emergency department with altered mental status and blood glucose (BG) of 22 mg/dL. Mental status improved after correction of hypoglycemia.He had multiple admissions for hypoglycemia, however, no history of diabetes mellitus, or use of hypoglycemia inducing medications. Home medications included Patiromer for hyperkalemia. Family history was remarkable for XLID type Nascimento in his brother and sister’s son. Imaging and laboratory studies conducted on prior admissions were inconclusive. Abdominal CT scan showed a 6mm cyst in the head of the pancreas, but no mass. A 72-hour fast after holding dextrose infusion did not yield a clear biochemical differential. BG 51 mg/dL, Insulin <0.5 (3.0–25 mU/L), C-peptide 0.6 (1.1–4.4 ng/mL), pro-insulin 3.2 (0.0–10.0 pmol/L), β-hydroxybutyrate 0.2 (<0.6 mmol/L). BG increased to greater than 25 mg/dL with 1 mg IV glucagon. Insulin antibody was negative (<5 uU/ml). IGF-1, IGF-2 were low at 17 (49–188 ng/mL) and 142 (333-967ng/mL) respectively. Thyroid function and ACTH stimulation test were within normal limits. Aldosterone <0.1(0.0–30 ng/dL), renin 0.195 (0.167–5.38 ng/mL/hr). Urine metabolic screen, urine amino acid screen, plasma amino acid screen and white cell lysosomal enzymes were normal for the nephew and not performed in our patient. The patient’s family requested not pursuing a repeat 72-hour fast, additional imaging or invasive procedures. Dexamethasone 0.5mg orally at bedtime was started which improved blood sugars and patient was discharged. He presented 2 weeks later with recurrent hypoglycemia. Dexamethasone was titrated to 1.5 mg with no improvement. Diazoxide 3mg/kg/day was subsequently started while dexamethasone was tapered and discontinued. Hypoglycemia did not recur.Conclusion: This is the first case report describing spontaneous hypoglycemia in an individual with XLID type Nascimento. Our patient also had hyporeninemic hypoaldosteronism which raises the question of endocrine abnormalities as a manifestation of XLID type Nascimento and if hypoglycemia is an inborn error of metabolism in this patient.