PMID- 32157856
OWN - NLM
STAT- MEDLINE
DCOM- 20210823
LR  - 20211204
IS  - 1308-5735 (Electronic)
IS  - 1308-5727 (Print)
VI  - 12
IP  - 4
DP  - 2020 Nov 25
TI  - The Effectiveness of Sirolimus Treatment in Two Rare Disorders with Nonketotic 
      Hypoinsulinemic Hypoglycemia: The Role of mTOR Pathway.
PG  - 439-443
LID - 10.4274/jcrpe.galenos.2020.2019.0084 [doi]
AB  - Nonketotic-hypoinsulinemic hypoglycemia (NkHH) is a very rare problem 
      charcterized by increase in glucose consumption without hyperinsulinism. This 
      disorder has mainly been reported in cases with AKT2 mutation and rarely in cases 
      with PTEN mutation. In cases with PTEN or AKT2 mutation, there is no effective 
      therapy other than frequent feeding to counter hypoglycemia. The mammalian target 
      of rapamicin (mTOR) inhibitor, sirolimus, has been used in hyperinsulinemic 
      hypoglycemia that was unresponsive to other medical treatment. In the insulin 
      signaling pathway, both AKT2 and PTEN function upstream of mTOR. However, the 
      role of Sirolimus on hypoglycemia in AKT2 and PTEN mutations is unknown. Case 1: 
      Six month-old female with AKT2 mutation [c.49G>A (p.E17K)] and evidence of NkHH. 
      Frequent feeding was unsuccesful in correcting hypoglycemia and her proptosis 
      continued to worsen. Sirolimus treatment was started at three years of age. 
      Subsequently, blood glucose (BG) levels increased to normal levels. Case 2: In a 
      male with PTEN mutation (p.G132V (c.395G>T), persistent NkHH started at 16 years 
      of age (fasting BG: 27 mg/dL, fasting insulin 1.5 mmol/L, while ketone negative). 
      Sirolimus treatment was started and hypoglycemia was succesfully controlled. NkHH 
      is a very rare and serious disorder which is challenging, both for diagnosis and 
      treatment. Additionally, AKT2 and PTEN mutations may result in NkHH. Sirolimus 
      treatment, through mTOR inhibition, appeared to be effectively controlling the 
      peristent hypoglycemia and may be a life-saving therapy in this NkHH due to AKT2 
      and PTEN mutations.
FAU - Siklar, Zeynep
AU  - Siklar Z
AUID- ORCID: 0000-0003-0921-2694
AD  - Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, 
      Ankara, Turkey
FAU - Cetin, Tugba
AU  - Cetin T
AUID- ORCID: 0000-0001-7702-8296
AD  - Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, 
      Ankara, Turkey
FAU - Cakar, Nilgun
AU  - Cakar N
AUID- ORCID: 0000-0002-1853-0101
AD  - Ankara University Faculty of Medicine, Department of Pediatric Reumatology, 
      Ankara, Turkey
FAU - Berberoglu, Merih
AU  - Berberoglu M
AUID- ORCID: 0000-0003-3102-0242
AD  - Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, 
      Ankara, Turkey
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20200311
PL  - Turkey
TA  - J Clin Res Pediatr Endocrinol
JT  - Journal of clinical research in pediatric endocrinology
JID - 101519456
RN  - 0 (Immunosuppressive Agents)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
MH  - Adolescent
MH  - Congenital Hyperinsulinism/*drug therapy/metabolism/pathology
MH  - Female
MH  - Humans
MH  - Hypoglycemia/*drug therapy/metabolism/pathology
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Infant
MH  - Male
MH  - Prognosis
MH  - Signal Transduction
MH  - Sirolimus/*therapeutic use
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC7711646
OTO - NOTNLM
OT  - *AKT2
OT  - *PTEN
OT  - *treatment
OT  - sirolimus
OT  - hypoglycemia
EDAT- 2020/03/12 06:00
MHDA- 2021/08/24 06:00
PMCR- 2020/12/01
CRDT- 2020/03/12 06:00
PHST- 2020/03/12 06:00 [entrez]
PHST- 2020/03/12 06:00 [pubmed]
PHST- 2021/08/24 06:00 [medline]
PHST- 2020/12/01 00:00 [pmc-release]
AID - 36223 [pii]
AID - 10.4274/jcrpe.galenos.2020.2019.0084 [doi]
PST - ppublish
SO  - J Clin Res Pediatr Endocrinol. 2020 Nov 25;12(4):439-443. doi: 
      10.4274/jcrpe.galenos.2020.2019.0084. Epub 2020 Mar 11.