Objectives: Forkhead box A2 (Foxa2) is a transcription factor that plays a key role in foregut, pancreatic and central nervous system development. Here, we describe a 7 years old boy whose phenotype is consistent with FOXA2 defect.
Case: A 3 months old boy was referred for recurrent hypoglycemic events. He was born to unrelated parents at term with a birth weight of 3690 gr. At 6 hours of life he had severe hypoglycemia (venous glucose= 5mg/dl). Shortly after discharge, he was re-admitted to emergency department with cardiovascular collapse with an undetectable blood glucose level. Other biochemical measurements were consistent with hypopituitarism (cortisol: 3mcg/dl, growth hormone: 0.6 mcg/L, b-hydroxybutyrate 0.3 mmol/L, insulin 1.2 mU/L). Hydrocortisone and growth hormone replacement was initiated. He also had central hypothyroidism (TSH: 7mU/L (1.12-8.21); fT4:0.61 ng/dl (0.71-1.96) ) and low prolactin levels (4.64 ng/ml). MRI of the pituitary gland revealed pituitary agenesis. On his initial examination height SDS was -1.19 (57cm), weight SDS was -1.56 (4.8kg). He was noted to have wide nasal bridge, bulbous nasal tip and smooth philtrum, bilateral cryptorchidism, micropenis and mild developmental delay. Abdominal ultrasonography revealed polysplenia. Abdominal MRI showed midline liver, situs inversus abdominalis, dorsal pancreatic agenesis, retroaortic left renal vein and inferior vena cava with azygos continuation. At two years old he was diagnosed with epilepsy and at 5 years with diabetes insipidus. At 5 years 8 months he developed postprandial glycemia and upper normal HbA1c (5.7%) with negative autoantibodies against GADA, IAA, ICA. The oral glucose tolerance test showed impaired glucose tolerance. FOXA2 mutation was considered in the etiology and the result of genetic testing for FOXA2 is pending.
Conclusions: To date, seven cases from six unrelated families were reported to have FOXA2 mutations. All of these patients exhibited dysfunction in the glucose regulation and pituitary hormone deficiencies with varying degrees of gastrointestinal and vascular abnormalities. One patient with a complete deletion of FOXA2 gene presented with an interrupted inferior vena cava (IVC), midline liver, biliary atresia and malrotation but without hypopituitarism. Our patient had hypopituitarism, IGT, vascular and intestinal abnormalities. Also our case and one case in the literature has a phenotype that shows a transition from neonatal hypoglycemia to early childhood hyperglycemia. Our patient had dorsal pancreatic agenesis which has not been described previously. Further description of these cases will highlight to the development of the pituitary and pancreas.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology