Sirolimus in the treatment of three infants with diffuse congenital hyperinsulinism.

Abstract

BACKGROUND:

Congenital hyperinsulinism (CHI) is a major cause of persistent hypoglycemia and brain damage. Therapeutic strategies to avoid near total pancreatectomy in patients who are unresponsive to maximum doses of diazoxide and octreotide remain to be identified, although sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used successfully to treat diffuse type CHI.

CASE PRESENTATION:

We used sirolimus to treat three infants with diffuse CHI. Diagnosis was confirmed clinically, biochemically and by genetic testing. Homozygous mutations in KCNJ11, ABCC8 and KCNJ11 were identified in infants 1, 2 and 3, respectively. Each infant had received the therapy for at least 2 months with close monitoring of glycemic response, serum insulin and C-peptide. None of the infants responded to the therapy.

CONCLUSIONS:

We conclude that sirolimus is less effective in the treatment of diffuse CHI in patients with severe mutations in the homozygous state compared with those with the mutations in the heterozygous.

• Authors: Rana Al-Balwi, Mohsen Al-Atawi, Ahlam Al-Otaibi, Omar Babiker, Angham Al-Mutair
• Journal: Journal of pediatric endocrinology & metabolism : JPEM (J Pediatr Endocrinol Metab) Vol. 30 Issue 9 Pg. 1013-1017 (Aug 28 2017) ISSN: 2191-0251 [Electronic] Germany
• PMID: 28787272 (Publication Type: Case Reports)

Chemical References

• ABCC8 protein, human
• Blood Glucose
• Kir6.2 channel
• Potassium Channels, Inwardly Rectifying
• Sulfonylurea Receptors
• Sirolimus

Topics

• Blood Glucose
• Congenital Hyperinsulinism (blood, drug therapy, genetics)
• Female
• Humans
• Infant
• Male
• Mutation
• Potassium Channels, Inwardly Rectifying (genetics)
• Sirolimus (therapeutic use)
• Sulfonylurea Receptors (genetics)
• Treatment Outcome