Successful Treatment of Hypoglycemia With Alpelisib in Pediatric Patients With PIK3CA-Related Overgrowth Spectrum

Activating mutations in the PIK3CA gene, causing phosphoinositide 3-kinase (PI3K) hyperactivation, are rare causes of hypoglycemia. We report the novel use of alpelisib (a PI3K inhibitor) for the treatment of hypoketotic, hypoinsulinemic hypoglycemia in 2 children with PIK3CA-related overgrowth spectrum (PROS). Patient 1 was a 7-month-old girl who presented with a hypoglycemic seizure. Despite nutritional management including continuous feeds, she continued to have frequent hypoglycemia. At age 2.8 years, alpelisib was started at 50 mg daily and titrated to 100 mg daily. She was weaned off nocturnal continuous feeds by 8 months. She developed colitis when the alpelisib dose was increased to 125 mg, but this resolved with a dose decrease and medical management. At age 5.3 years, she was doing well with rare hypoglycemia. Her accelerated growth stabilized. Patient 2 was a 3-year-old boy who developed hypoglycemia in early infancy. Alpelisib 50 mg daily was started due to recurrent hypoglycemia despite nutritional management. He came off continuous feeds after 4 months, with decreased hypoglycemia frequency. At age 4.5 years, he had not experienced side effects from treatment. In conclusion, alpelisib appears to be effective in decreasing PROS-related hypoglycemia frequency and severity and should be considered for refractory hypoglycemia in this condition.