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Hyperinsulinemic hypoglycemia, familial, 2(HHF2)

MedGen UID:
419173
Concept ID:
C2931833
Disease or Syndrome
Synonyms: HYPERINSULINEMIC HYPOGLYCEMIA, PERSISTENT; HYPERINSULINISM, NEONATAL; KCNJ11-Related Hyperinsulinism
 
Gene (location): KCNJ11 (11p15.1)
 
Monarch Initiative: MONDO:0011153
OMIM®: 601820

Definition

Congenital hyperinsulinism is a condition that causes individuals to have abnormally high levels of insulin. Insulin is a hormone that helps control levels of blood glucose, also called blood sugar. People with this condition have frequent episodes of low blood glucose (hypoglycemia). In infants and young children, these episodes are characterized by a lack of energy (lethargy), irritability, or difficulty feeding. Repeated episodes of low blood glucose increase the risk for serious complications such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, and coma.

The severity of congenital hyperinsulinism varies widely among affected individuals, even among members of the same family. About 60 percent of infants with this condition experience a hypoglycemic episode within the first month of life. Other affected children develop hypoglycemia by early childhood. Unlike typical episodes of hypoglycemia, which occur most often after periods without food (fasting) or after exercising, episodes of hypoglycemia in people with congenital hyperinsulinism can also occur after eating. [from MedlinePlus Genetics]

Clinical features

From HPO
Large for gestational age
MedGen UID:
341215
Concept ID:
C1848395
Finding
The term large for gestational age applies to babies whose birth weight lies above the 90th percentile for that gestational age.
Nesidioblastosis
MedGen UID:
45047
Concept ID:
C0027773
Disease or Syndrome
An abnormality of pancreatic beta cells characterized by a proliferation of abnormal beta cells throughout the entire pancreas, with enlarged islet size and number (hypertrophic islets), increased periductular islets, enlarged beta-cell nuclei and abundant clear cytoplasm. Occasionally beta cells with pleomorphic nuclei, ductuloinsular complexes, and neoformation of islets from ducts are observed.
Pancreatic islet-cell hyperplasia
MedGen UID:
108598
Concept ID:
C0597167
Finding
Hyperplasia of the islets of Langerhans, i.e., of the regions of the pancreas that contain its endocrine cells.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Hyperinsulinemic hypoglycemia
MedGen UID:
351247
Concept ID:
C1864903
Disease or Syndrome
An increased concentration of insulin combined with a decreased concentration of glucose in the blood.

Professional guidelines

PubMed

De Leon DD, Arnoux JB, Banerjee I, Bergada I, Bhatti T, Conwell LS, Fu J, Flanagan SE, Gillis D, Meissner T, Mohnike K, Pasquini TLS, Shah P, Stanley CA, Vella A, Yorifuji T, Thornton PS
Horm Res Paediatr 2024;97(3):279-298. Epub 2023 Jul 14 doi: 10.1159/000531766. PMID: 37454648Free PMC Article
Roeper M, Hoermann H, Kummer S, Meissner T
Front Endocrinol (Lausanne) 2023;14:1179102. Epub 2023 Jun 8 doi: 10.3389/fendo.2023.1179102. PMID: 37361517Free PMC Article
Demirbilek H, Hussain K
J Clin Res Pediatr Endocrinol 2017 Dec 30;9(Suppl 2):69-87. Epub 2017 Dec 27 doi: 10.4274/jcrpe.2017.S007. PMID: 29280746Free PMC Article

Recent clinical studies

Etiology

Roeper M, Hoermann H, Kummer S, Meissner T
Front Endocrinol (Lausanne) 2023;14:1179102. Epub 2023 Jun 8 doi: 10.3389/fendo.2023.1179102. PMID: 37361517Free PMC Article
Brar PC, Heksch R, Cossen K, De Leon DD, Kamboj MK, Marks SD, Marshall BA, Miller R, Page L, Stanley T, Mitchell D, Thornton P
J Clin Endocrinol Metab 2020 Dec 1;105(12) doi: 10.1210/clinem/dgaa543. PMID: 32810255
Douillard C, Jannin A, Vantyghem MC
Ann Endocrinol (Paris) 2020 Jun;81(2-3):110-117. Epub 2020 Apr 10 doi: 10.1016/j.ando.2020.04.003. PMID: 32409005
Rosenfeld E, Ganguly A, De Leon DD
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):682-692. Epub 2019 Aug 14 doi: 10.1002/ajmg.c.31737. PMID: 31414570Free PMC Article
Demirbilek H, Hussain K
J Clin Res Pediatr Endocrinol 2017 Dec 30;9(Suppl 2):69-87. Epub 2017 Dec 27 doi: 10.4274/jcrpe.2017.S007. PMID: 29280746Free PMC Article

Diagnosis

Casertano A, Rossi A, Fecarotta S, Rosanio FM, Moracas C, Di Candia F, Parenti G, Franzese A, Mozzillo E
Front Endocrinol (Lausanne) 2021;12:684011. Epub 2021 Aug 2 doi: 10.3389/fendo.2021.684011. PMID: 34408725Free PMC Article
Gϋemes M, Rahman SA, Kapoor RR, Flanagan S, Houghton JAL, Misra S, Oliver N, Dattani MT, Shah P
Rev Endocr Metab Disord 2020 Dec;21(4):577-597. doi: 10.1007/s11154-020-09548-7. PMID: 32185602Free PMC Article
De Franco E, Saint-Martin C, Brusgaard K, Knight Johnson AE, Aguilar-Bryan L, Bowman P, Arnoux JB, Larsen AR, Sanyoura M, Greeley SAW, Calzada-León R, Harman B, Houghton JAL, Nishimura-Meguro E, Laver TW, Ellard S, Del Gaudio D, Christesen HT, Bellanné-Chantelot C, Flanagan SE
Hum Mutat 2020 May;41(5):884-905. Epub 2020 Feb 17 doi: 10.1002/humu.23995. PMID: 32027066Free PMC Article
Rosenfeld E, Ganguly A, De Leon DD
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):682-692. Epub 2019 Aug 14 doi: 10.1002/ajmg.c.31737. PMID: 31414570Free PMC Article
Demirbilek H, Hussain K
J Clin Res Pediatr Endocrinol 2017 Dec 30;9(Suppl 2):69-87. Epub 2017 Dec 27 doi: 10.4274/jcrpe.2017.S007. PMID: 29280746Free PMC Article

Therapy

De Leon DD, Arnoux JB, Banerjee I, Bergada I, Bhatti T, Conwell LS, Fu J, Flanagan SE, Gillis D, Meissner T, Mohnike K, Pasquini TLS, Shah P, Stanley CA, Vella A, Yorifuji T, Thornton PS
Horm Res Paediatr 2024;97(3):279-298. Epub 2023 Jul 14 doi: 10.1159/000531766. PMID: 37454648Free PMC Article
Giri D, Hawton K, Senniappan S
J Pediatr Endocrinol Metab 2022 Mar 28;35(3):279-296. Epub 2021 Sep 21 doi: 10.1515/jpem-2021-0369. PMID: 34547194
Brar PC, Heksch R, Cossen K, De Leon DD, Kamboj MK, Marks SD, Marshall BA, Miller R, Page L, Stanley T, Mitchell D, Thornton P
J Clin Endocrinol Metab 2020 Dec 1;105(12) doi: 10.1210/clinem/dgaa543. PMID: 32810255
Gomes-Porras M, Cárdenas-Salas J, Álvarez-Escolá C
Int J Mol Sci 2020 Feb 29;21(5) doi: 10.3390/ijms21051682. PMID: 32121432Free PMC Article
Muir AB, Rose SR
Clin Perinatol 2018 Mar;45(1):xvii-xviii. Epub 2017 Dec 1 doi: 10.1016/j.clp.2017.11.004. PMID: 29406016

Prognosis

Velde CD, Reigstad H, Tjora E, Guthe HJT, Hansen EV, Molven A, Njølstad PR
Tidsskr Nor Laegeforen 2023 Dec 12;143(18) Epub 2023 Dec 11 doi: 10.4045/tidsskr.23.0425. PMID: 38088279
Rosenfeld E, Ganguly A, De Leon DD
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):682-692. Epub 2019 Aug 14 doi: 10.1002/ajmg.c.31737. PMID: 31414570Free PMC Article
Minakova E, Chu A
Pediatr Ann 2017 Nov 1;46(11):e409-e414. doi: 10.3928/19382359-20171020-01. PMID: 29131920
Snider KE, Becker S, Boyajian L, Shyng SL, MacMullen C, Hughes N, Ganapathy K, Bhatti T, Stanley CA, Ganguly A
J Clin Endocrinol Metab 2013 Feb;98(2):E355-63. Epub 2012 Dec 28 doi: 10.1210/jc.2012-2169. PMID: 23275527Free PMC Article
Arnoux JB, de Lonlay P, Ribeiro MJ, Hussain K, Blankenstein O, Mohnike K, Valayannopoulos V, Robert JJ, Rahier J, Sempoux C, Bellanné C, Verkarre V, Aigrain Y, Jaubert F, Brunelle F, Nihoul-Fékété C
Early Hum Dev 2010 May;86(5):287-94. Epub 2010 Jun 13 doi: 10.1016/j.earlhumdev.2010.05.003. PMID: 20550977

Clinical prediction guides

Rosenfeld E, Ganguly A, De Leon DD
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):682-692. Epub 2019 Aug 14 doi: 10.1002/ajmg.c.31737. PMID: 31414570Free PMC Article
Vajravelu ME, De León DD
Curr Opin Pediatr 2018 Aug;30(4):568-575. doi: 10.1097/MOP.0000000000000645. PMID: 29750770Free PMC Article
Minakova E, Chu A
Pediatr Ann 2017 Nov 1;46(11):e409-e414. doi: 10.3928/19382359-20171020-01. PMID: 29131920
Snider KE, Becker S, Boyajian L, Shyng SL, MacMullen C, Hughes N, Ganapathy K, Bhatti T, Stanley CA, Ganguly A
J Clin Endocrinol Metab 2013 Feb;98(2):E355-63. Epub 2012 Dec 28 doi: 10.1210/jc.2012-2169. PMID: 23275527Free PMC Article
Giurgea I, Bellanné-Chantelot C, Ribeiro M, Hubert L, Sempoux C, Robert JJ, Blankenstein O, Hussain K, Brunelle F, Nihoul-Fékété C, Rahier J, Jaubert F, de Lonlay P
Horm Res 2006;66(6):289-96. Epub 2006 Sep 26 doi: 10.1159/000095938. PMID: 17003566

Recent systematic reviews

Jeffery TC, Chang AB, Conwell LS
Cochrane Database Syst Rev 2023 Jan 10;1(1):CD002010. doi: 10.1002/14651858.CD002010.pub5. PMID: 36625789Free PMC Article
Perge K, Nicolino M
Rev Endocr Metab Disord 2022 Oct;23(5):1063-1078. Epub 2022 Aug 23 doi: 10.1007/s11154-022-09749-2. PMID: 35996042
Kostopoulou E, Dastamani A, Güemes M, Clement E, Caiulo S, Shanmugananda P, Dattani M, Gilbert C, Hurst JA, Shah P
Clin Endocrinol (Oxf) 2021 Mar;94(3):399-412. Epub 2021 Jan 31 doi: 10.1111/cen.14393. PMID: 33345357
Ma D, Chen Z, Wang Y, Yu X, Xin Q, Chen Y
Eur J Clin Nutr 2021 Aug;75(8):1193-1204. Epub 2020 Dec 17 doi: 10.1038/s41430-020-00831-z. PMID: 33328601
Shah R, Harding J, Brown J, McKinlay C
Neonatology 2019;115(2):116-126. Epub 2018 Nov 8 doi: 10.1159/000492859. PMID: 30408811

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