Hyperinsulinemic Hypoglycemia in Childhood
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https://doi.org/10.58600/eurjther1758Keywords:
Hyperinsulinemic Hypoglycemia, Childhood, KATP gene, Diazoxide, OctreotideAbstract
Hyperinsulinemic Hypoglycemia (HH) is the most common cause of permanent hypoglycemia, especially in the neonatal period. Childhood HH is mostly related to genes encoding proteins in the insulin secretion pathways, and may also be seen in syndromes such as Beckwidth Wiedemann, Kabuki, and Turner. The majority of congenital HH cases are the result of KATP channel gene defect. Most of these cases are unresponsive to diazoxide treatment. In this review, recent genetic studies and recent updates in treatment options in childhood HH are reviewed.
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Demirbilek H, Hussain K (2017) Congenital Hyperinsulinism: Diagnosis and Treatment Update. J Clin Res Pediatr Endocrinol. 9(Suppl 2):69-87. https://doi.org/10.4274/jcrpe.2017.S007
Shah P, Rahman SA, Demirbilek H, Güemes M, Hussain K (2017) Hyperinsulinaemic hypoglycaemia in children and adults. Lancet Diabetes Endocrinol. 5(9):729-742. https://doi.org/10.1016/S2213-8587(16)30323-0
Martino M, Sartorelli J, Gragnaniello V, Burlina A (2022) Congenital hyperinsulinism in clinical practice: From biochemical pathophysiology to new monitoring techniques. Front Pediatr. 23;10:901338. https://doi.org/10.3389/fped.2022.901338
Thompson-Branch A, Havranek T (2017) Neonatal Hypoglycemia. Pediatr Rev. 38(4):147-157. https://doi.org/10.1542/pir.2016-0063
Stanley CA, Thornton PS, De Leon DD (2023) New approaches to screening and management of neonatal hypoglycemia based on improved understanding of the molecular mechanism of hypoglycemia. Front Pediatr. 10;11:1071206. https://doi.org/10.3389/fped.2023.1071206
Hoe FM, Thornton PS, Wanner LA, Steinkrauss L, Simmons RA, Stanley CA (2006) Clinical features and insulin regulation in infants with a syndrome of prolonged neonatal hyperinsulinism. J Pediatr. 148(2):207-212. https://doi.org/10.1016/j.jpeds.2005.10.002
Zenker M, Mohnike K, Palm K (2023) Syndromic forms of congenital hyperinsulinism. Front Endocrinol (Lausanne). 30;14:1013874. https://doi.org/10.3389/fendo.2023.1013874
DeBaun MR, King AA, White N (2000) Hypoglycemia in Beckwith-Wiedemann syndrome. Seminars in perinatology. 24(2):164-71. https://doi.org/10.1053/sp.2000.6366
Adachi H, Takahashi I, Higashimoto K, Tsuchida S, Noguchi A, Tamura H, et al. (2013) Congenital hyperinsulinism in an infant with paternal uniparental disomy on chromosome 11p15: few clinical features suggestive of Beckwith-Wiedemann syndrome. Endocrine journal. 60(4):403-8. https://doi.org/10.1507/endocrj.EJ12-0242
Shuman C, Smith AC, Steele L, Ray PN, Clericuzio C, Zackai E, et al. (2006) Constitutional UPD for chromosome 11p15 in individuals with isolated hemihyperplasia is associated with high tumor risk and occurs following assisted reproductive technologies. American journal of medical genetics Part A. 140(14):1497-503. https://doi.org/10.1002/ajmg.a.31323
Teh MM, Dunn JT, Choudhary P, Samarasinghe Y, Macdonald I, O’Doherty M, et al. (2010) Evolution and resolution of human brain perfusion responses to the stress of induced hypoglycemia. Neuroimage. 53:584–592. https://doi.org/10.1016/j.neuroimage.2010.06.033
Senniappan S, Shanti B, James C, Hussain K (2012) Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management. J Inherit Metab Dis. 35:589–601. https://doi.org/10.1007/s10545-011-9441-2
Demirbilek H, Arya VB, Ozbek MN, Akinci A, Dogan M, Demirel F, Houghton J, Kaba S, Guzel F, Baran RT, Unal S, Tekkes S, Flanagan SE, Ellard S, Hussain K (2014) Clinical characteristics and phenotype-genotype analysis in Turkish patients with congenital hyperinsulinism; predominance of recessive KATP channel mutations. Eur J Endocrinol. 170(6):885-892. https://doi.org/10.1530/EJE-14-0045
Kane C, Shepherd RM, Squires PE, Johnson PR, James RF, Milla PJ, et al. (1996) Loss of functional KATP channels in pancreatic beta-cells causes persistent hyperinsulinemic hypoglycemia of infancy. Nat Med. 2(12):1344-7. https://doi.org/10.1038/nm1296-1344
Glaser B (2011) Lessons in human biology from a monogenic pancreatic β cell disease. J Clin Invest. 121(10):3821-5. https://doi.org/10.1172/JCI60002
Flanagan SE, Kapoor RR, Banerjee I, Hall C, Smith VV, Hussain K, et al. (2011) Dominantly acting ABCC8 mutations in patients with medically unresponsive hyperinsulinaemic hypoglycaemia. Clin Genet. 79(6):582-7. https://doi.org/10.1111/j.1399-0004.2010.01476.x
Torekov SS, Iepsen E, Christiansen M, Linneberg A, Pedersen O, Holst JJ, et al. (2014) KCNQ1 long QT syndrome patients have hyperinsulinemia and symptomatic hypoglycemia. Diabetes. 63(4):1315-25. https://doi.org/10.2337/db13-1454
Scholl UI, Goh G, Stolting G, de Oliveira RC, Choi M, Overton JD, et al. (2013) Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nature genetics. 45(9):1050-4. https://doi.org/10.1038/ng.2695
Flanagan SE, Vairo F, Johnson MB, Caswell R, Laver TW, Lango Allen H, et al. (2017) A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia. Pediatric diabetes. 18(4):320-3. https://doi.org/10.1111/pedi.12512
Otonkoski T, Kaminen N, Ustinov J, Lapatto R, Meissner T, Mayatepek E, et al. (2003) Physical exercise-induced hyperinsulinemic hypoglycemia is an autosomal-dominant trait characterized by abnormal pyruvate-induced insulin release. Diabetes. 52(1):199-204. https://doi.org/10.2337/diabetes.52.1.199
Stanley CA (2004) Hyperinsulinism/hyperammonemia syndrome: insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism. Molecular genetics and metabolism. 81:45-51. https://doi.org/10.1016/j.ymgme.2003.10.013
Bahi-Buisson N, Roze E, Dionisi C, Escande F, Valayannopoulos V, Feillet F, et al. (2008) Neurological aspects of hyperinsulinism-hyperammonaemia syndrome. Dev Med Child Neurol. 50(12):945-949. https://doi.org/10.1111/j.1469-8749.2008.03114.x
Kapoor RR, James C, Flanagan SE, Ellard S, Eaton S, Hussain K (2009) 3-Hydroxyacyl-coenzyme A dehydrogenase deficiency and hyperinsulinemic hypoglycemia: characterization of a novel mutation and severe dietary protein sensitivity. J Clin Endocrinol Metab. 94(7):2221-2225. https://doi.org/10.1210/jc.2009-0423
Martins E, Cardoso ML, Rodrigues E, Barbot C, Ramos A, Bennett MJ, et al. (2011) Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: the clinical relevance of an early diagnosis and report of four new cases. Journal of inherited metabolic disease. 34(3):835-842. https://doi.org/10.1007/s10545-011-9287-7
Glaser B, Kesavan P, Heyman M, Davis E, Cuesta A, Buchs A, et al. (1998) Familial hyperinsulinism caused by an activating glucokinase mutation. N Engl J Med. 338(4):226-230. https://doi.org/10.1056/NEJM199801223380404
Martinez R, Gutierrez-Nogues A, Fernandez-Ramos C, Velayos T, Vela A, Navas MA, et al. (2017) Heterogeneity in phenotype of hyperinsulinism caused by activating glucokinase mutations: a novel mutation and its functional characterization. Clinical endocrinology. 86(6):778-783. https://doi.org/10.1111/cen.13318
Gilis-Januszewska A, Bogusławska A, Kowalik A, Rzepka E, Soczówka K, Przybylik-Mazurek E, Głowa B, Hubalewska-Dydejczyk A (2021) Hyperinsulinemic Hypoglycemia in Three Generations of a Family with Glucokinase Activating Mutation, c.295T>C (p.Trp99Arg). Genes (Basel). 12(10):1566. https://doi.org/10.3390/genes12101566
Arya VB, Rahman S, Senniappan S, Flanagan SE, Ellard S, Hussain K (2014) HNF4A mutation: switch from hyperinsulinaemic hypoglycaemia to maturity-onset diabetes of the young, and incretin response. Diabet Med. 31(3):e11-15. https://doi.org/10.1111/dme.12369
Fajans SS, Bell GI (2007) Macrosomia and neonatal hypoglycaemia in RW pedigree subjects with a mutation (Q268X) in the gene encoding hepatocyte nuclear factor 4alpha (HNF4A). Diabetologia. 50(12):2600-2601. https://doi.org/10.1007/s00125-007-0833-7
Gao N, LeLay J, Vatamaniuk MZ, Rieck S, Friedman JR, Kaestner KH (2008) Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development. Genes & development. 22(24):3435-3448. https://doi.org/10.1101/gad.1752608
Giri D, Vignola ML, Gualtieri A, Scagliotti V, McNamara P, Peak M, et al. (2017) Novel FOXA2 mutation causes Hyperinsulinism, Hypopituitarism with Craniofacial and Endoderm-derived organ abnormalities. Human molecular genetics. 26(22):4315-4326. https://doi.org/10.1093/hmg/ddx318
Beltrand J, Caquard M, Arnoux JB, Laborde K, Velho G, Verkarre V, Rahier J, Brunelle F, Nihoul-Fékété C, Saudubray JM, Robert JJ, de Lonlay P (2012 ) Glucose metabolism in 105 children and adolescents after pancreatectomy for congenital hyperinsulinism. Diabetes Care. 35(2):198-203. https://doi.org/10.2337/dc11-1296
Avatapalle HB, Banerjee I, Shah S, Pryce M, Nicholson J, Rigby L, et al. (2013) Abnormal Neurodevelopmental Outcomes are Common in Children with Transient Congenital Hyperinsulinism. Frontiers in endocrinology. 4:60. https://doi.org/10.3389/fendo.2013.00060
Levy-Shraga Y, Pinhas-Hamiel O, Kraus-Houminer E, Landau H, Mazor-Aronovitch K, Modan-Moses D, et al. Cognitive and developmental outcome of conservatively treated children with congenital hyperinsulinism. JPEM. 2013;26(3-4):301-308. https://doi.org/10.1515/jpem-2012-0289
Neylon OM, Moran MM, Pellicano A, Nightingale M, O’Connell MA (2013) Successful subcutaneous glucagon use for persistent hypoglycaemia in congenital hyperinsulinism. JPEM. 26(11-12):1157-1161. https://doi.org/10.1515/jpem-2013-0115
Banerjee I, Forsythe L, Skae M, Avatapalle HB, Rigby L, Bowden LE, et al. (2016) Feeding Problems Are Persistent in Children with Severe Congenital Hyperinsulinism. Frontiers in endocrinology. 7:8. https://doi.org/10.3389/fendo.2016.00008
Yildizdas D, Erdem S, Küçükosmanoglu O, Yilmaz M, Yüksel B (2008) Pulmonary hypertension, heart failure and neutropenia due to diazoxide therapy. Adv Ther. 25(5):515-519. https://doi.org/10.1007/s12325-008-0049-3
Müller D, Zimmering M, Roehr CC (2004) Should nifedipine be used to counter low blood sugar levels in children with persistent hyperinsulinaemic hypoglycaemia? Arch Dis Child. 89(1):83-85. https://doi.org/10.1136/fn.89.1.F83
Welters A, Lerch C, Kummer S, Marquard J, Salgin B, Mayatepek E, Meissner T (2015) Long-term medical treatment in congenital hyperinsulinism: a descriptive analysis in a large cohort of patients from different clinical centers. Orphanet J Rare Dis. 10:150. https://doi.org/10.1186/s13023-015-0367-x
Senniappan S, Alexandrescu S, Tatevian N, Shah P, Arya V, Flanagan S, et al. (2014) Sirolimus therapy in infants with severe hyperinsulinemic hypoglycemia. N Engl J Med. 370(12):1131-1137. https://doi.org/10.1056/NEJMoa1310967
Haliloglu B, Tuzun H, Flanagan SE, Celik M, Kaya A, Ellard S, et al. (2018) Sirolimus-Induced Hepatitis in Two Patients with Hyperinsulinemic Hypoglycemia. Journal of clinical research in pediatric endocrinology. 10(3):279-283. https://doi.org/10.4274/jcrpe.5335
Szymanowski M, Estebanez MS, Padidela R, Han B, Mosinska K, Stevens A, et al. (2016) mTOR Inhibitors for the Treatment of Severe Congenital Hyperinsulinism: Perspectives on Limited Therapeutic Success. J Clin Endocrinol Metab. 101(12):4719-4729. https://doi.org/10.1210/jc.2016-2711
Peterson SM, Juliana CA, Hu CF, Chai J, Holliday C, Chan KY, Lujan Hernandez AG, Challocombe Z, Wang L, Han Z, Haas N, Stafford R, Axelrod F, Yuan TZ, De Leόn DD, Sato AK (2023) Optimization of a glucagon-like peptide 1 receptor antagonist antibody for treatment of hyperinsulinism. Diabetes. 26:db221039. https://doi.org/10.2337/db22-1039
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