ODP372 A Rare Case Of Cornelia de Lange Syndrome With Hyperinsulinism And Hypopituitarism

Abstract

Abstract Background Cornelia de Lange syndrome (CdLS) is characterized by slow growth with short stature, intellectual disability with developmental delays, distinctive facial features, and limb defects. Various genetic mutations have been associated with CdLS, with approximately 60% of cases having a mutation in the NIPBL gene. There are few published reports of endocrine disorders in individuals affected by CdLS. Clinical Case A four month old female was admitted for hypoglycemic seizures. She had previously undergone workup for CHARGE syndrome. Physical exam was remarkable for acrocephaly, malar hypoplasia, hypertelorism with downslanting eyes, hirsutism, and bradydactyly. During her hospitalization, she remained persistently hypoglycemic despite repeated dextrose boluses, prompting a scheduled fasting test. Results indicated severe hypoglycemia (37 mg/dL) with inappropriate suppression of beta-hydroxybutyrate (0. 08 mmol/L) and negative urine ketones. Her glucagon stimulation test result showed an exaggerated increase of the glucose greater than 30 mg/dL after glucagon administration (glucose was 31 mg/dL at the start of the test; peak glucose was 77 mg/dL after receiving 0. 03 mg/kg of glucagon), indicating excessive glycogen stores. These findings were consistent with hyperinsulinism. Furthermore, she was found to have an undetectable cortisol (<1. 0 ug/dL) with hypoglycemia, prompting a low dose ACTH stimulation test with results consistent with central adrenal insufficiency (baseline ACTH: <5 pg/mL, baseline cortisol: <1. 0 ug/dL, peak cortisol after receiving 10 micrograms of cosyntropin was 1.1 ug/dL). Additional evaluation revealed a low free T4 (0.5 ng/dL). Interestingly, the initial TSH was 6.46 uIU/mL, which later became undetectable (<0. 05 uIU/mL), consistent with central hypothyroidism. Ultimately, a brain MRI showed sella turcica hypoplasia with absence of the dorsum sella as well as corpus callosum hypoplasia and a thin pituitary infundibulum. The child was treated with diazoxide, hydrocortisone, and levothyroxine with improvement in clinical course. Genetic testing eventually confirmed CdLS, showing a heterozygous variant mutation (c.8077_8079dupGAC: p. D2693dup) in exon 47 of NIPBL gene, classified as autosomal dominant. Conclusion There are very few clinical reports that mention either hyperinsulinism or hypopituitarism in an individual affected by CdLS. This patient is a rare documented case of CdLS presenting with both hyperinsulinism and hypopituitarism. Further understanding of the different genetic mutations seen with CdLS could help identify atypical forms of CdLS associated with endocrinopathies and more clearly direct unifying treatment. Presentation: No date and time listed