IMPE Abstracts

BLSS, male, second child of young, healthy, non-consanguineous parents, no family history of comorbidities. He was born by cesarean delivery due to polyhydramnios, 41 weeks of gestational age, with adequate weight and length. Apgar 7/9. Identified at birth micropenis: 1.5cm, bilateral auricular pit, sacral pit and 2mm atrial septal defect. At 4 days of life, he presented persistent neonatal jaundice (indirect bilirubin: 16.6mg/dL, direct bilirubin: 0.6mg/dL) and hypoglycemia (serum glucose of 27mg/dL), requiring a maximum glucose infusion of 9mg/kg /min. A karyotype was performed (20 cells analyzed): 46, XY. Abdominal ecography, cranial tomography, quantitative dosage of amino acids and funduscopy without alterations. Neuromotor delay was observed: no cephalic support, visual contact or reaction to sound stimuli. At 2 months old: laboratorial data colected during hypoglicemia showed: growth hormone deficiency, central hypothyroidism, central hypocortisolsm and hyperinsulinism: Serum glucose: 51mg/dL, GH: 0.22mg/dL, ACTH 15 pg/ml, cortisol: 1.4 mg/dL, TSH: 5.88 mIU/L, Free T4: 0.53 ng/dL, Insulin 9.2 mg/dL. Second sample was colected: serum glucose of 32mg/dL, insulin: 4.8 mg/dL and ketonemia: 0.1 mg/dL. He also had low LH: 0.07mIU/ml and FSH: 0.82 mIU/ml and total testosterone: 13 ng/dL Cranial MRI: pituitary hypoplasia with ectopic neurohypophysis. Hydrocortisone 10mg/m²/day, levothyroxine 10mg/kg/day, diazoxide 15mg/kg/day, hydrochlorothiazide 7mg/kg/day and somatropin 0.1UI/kg/day, testosterone 25mg/monthly were started. At 4 months, he developed septic shock and died despite therapeutic interventions. In literature review, reports of similar cases associated with FOXA2 gene mutation were found. Patient's genome was collected and a deletion of approximately 3.8 Mb was detected in the chromosomal region 20p11.23-20p11.21, involving 13 protein-coding genes, 12 related to OMIM phenotype. Among them, FOXA2 is highlighted and related to hyperinsulinism and hypopituitarism. The coexistence of these two conditions is uncommon, with few case reports in the literature. This phenotype associated with a mutation in Forkhead box A2 (FOXA2), a transcription factor critical for multiple tissues function, including pancreatic beta cells, and pituitary development, is described. In some of the reports, involvement of other systems is described: gastrointestinal, pulmonary, cardiovascular, hepatic. Similar to the case above, an adequate therapeutic response to diazoxide and hormonal replacements are described.

Conclusion: An adequate and early diagnosis is crucial for proper treatment and reduction of sequelae. We emphasize the importance of the genetic study for etiological elucidation. This research was made possible through access to the data and findings generated by the Rare Genomes Project; http://www.genomasraros.com