PMID- 25518065
OWN - NLM
STAT- MEDLINE
DCOM- 20160126
LR  - 20220408
IS  - 2191-0251 (Electronic)
IS  - 0334-018X (Linking)
VI  - 28
IP  - 5-6
DP  - 2015 May
TI  - Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to 
      a compound heterozygous ABCC8 gene mutation.
PG  - 695-9
LID - 10.1515/jpem-2014-0371 [doi]
AB  - INTRODUCTION: Hyperinsulinaemic hypoglycaemia (HH) is the most common cause of 
      severe and persistent hypoglycaemia in neonates. The treatment of severe 
      diazoxide unresponsive HH involves near total pancreatectomy. Mammalian target of 
      rapamycin (mTOR) is a protein kinase that regulates cellular proliferation. mTOR 
      inhibitors are used in cancer patients and recently found to be effective in the 
      treatment of insulinoma and HH patients. CASE: A 36 weeks large for gestational 
      age neonate presented with severe hypoglycaemia on day 1 of life. The 
      hypoglycaemia screen confirmed HH and genetic testing revealed compound 
      heterozygous ABCC8 mutation, confirming diffuse disease. He was unresponsive to 
      the maximal dose of diazoxide (15 mg/kg/day), hence needed treatment with higher 
      concentration of intravenous glucose (25 mg/kg/min), intravenous glucagon and 
      subcutaneous octreotide (30 mug/kg/day) infusions to maintain normoglycaemia. 
      Sirolimus, a mTOR inhibitor, was commenced at 9 weeks of age following which he 
      showed a marked improvement in his glycaemic control. After 4 weeks of sirolimus 
      therapy, he was discharged home on subcutaneous octreotide injection (20 
      mug/kg/day) and oral sirolimus, thereby avoiding the need for a near total 
      pancreatectomy. CONCLUSION: We report the first case of compound heterozygous 
      ABCC8 mutation causing severe diffuse HH that responded to therapy with a mTOR 
      inhibitor.
FAU - Shah, Pratik
AU  - Shah P
FAU - Arya, Ved Bhushan
AU  - Arya VB
FAU - Flanagan, Sarah E
AU  - Flanagan SE
FAU - Morgan, Kate
AU  - Morgan K
FAU - Ellard, Sian
AU  - Ellard S
FAU - Senniappan, Senthil
AU  - Senniappan S
FAU - Hussain, Khalid
AU  - Hussain K
LA  - eng
GR  - 098395/WT_/Wellcome Trust/United Kingdom
GR  - MR/M023265/1/MRC_/Medical Research Council/United Kingdom
PT  - Case Reports
PT  - Journal Article
PL  - Germany
TA  - J Pediatr Endocrinol Metab
JT  - Journal of pediatric endocrinology & metabolism : JPEM
JID - 9508900
RN  - 0 (ABCC8 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Sulfonylurea Receptors)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Congenital Hyperinsulinism/*drug therapy/genetics
MH  - *Heterozygote
MH  - Humans
MH  - Infant, Newborn
MH  - Insulin/*blood
MH  - Male
MH  - *Mutation
MH  - Sirolimus/*therapeutic use
MH  - Sulfonylurea Receptors/*genetics
EDAT- 2014/12/18 06:00
MHDA- 2016/01/27 06:00
CRDT- 2014/12/18 06:00
PHST- 2014/08/31 00:00 [received]
PHST- 2014/10/22 00:00 [accepted]
PHST- 2014/12/18 06:00 [entrez]
PHST- 2014/12/18 06:00 [pubmed]
PHST- 2016/01/27 06:00 [medline]
AID - /j/jpem.ahead-of-print/jpem-2014-0371/jpem-2014-0371.xml [pii]
AID - 10.1515/jpem-2014-0371 [doi]
PST - ppublish
SO  - J Pediatr Endocrinol Metab. 2015 May;28(5-6):695-9. doi: 10.1515/jpem-2014-0371.