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  • CN043604 has been replaced by C3888018, showing C3888018

Familial hyperinsulinism(PHHI; PHHI)

MedGen UID:
854723
Concept ID:
C3888018
Congenital Abnormality; Disease or Syndrome
Synonyms: Congenital Hyperinsulinism; Congenital Hyperinsulinisms; Familial Hyperinsulinism; Familial Hyperinsulinisms; Hyperinsulinemia Hypoglycemia of Infancy; Hyperinsulinemic Hypoglycemia, Persistent; Hyperinsulinemic Hypoglycemias, Persistent; Hyperinsulinism, Congenital; Hyperinsulinism, Familial; Hyperinsulinism, Neonatal; Hyperinsulinisms, Congenital; Hyperinsulinisms, Familial; Hyperinsulinisms, Neonatal; Hypoglycemia, Hyperinsulinemic, of Infancy; Hypoglycemia, Persistent Hyperinsulinemic; Hypoglycemia, PHHI; Hypoglycemias, Persistent Hyperinsulinemic; Hypoglycemias, PHHI; Infancy Hyperinsulinemia Hypoglycemia; Infancy Hyperinsulinemia Hypoglycemias; Neonatal Hyperinsulinism; Neonatal Hyperinsulinisms; Persistent Hyperinsulinemia Hypoglycemia of Infancy; Persistent Hyperinsulinemic Hypoglycemia; Persistent Hyperinsulinemic Hypoglycemias; PHHI Hypoglycemia; PHHI Hypoglycemias
SNOMED CT: Congenital hyperinsulinism (360339005); Persistent hyperinsulinemic hypoglycemia of infancy (360339005)
 
Gene (location): HNF4A (20q13.12)
Related genes: ABCC8, SLC16A1, KCNJ11, INSR, HADH, GLUD1, GCK
OMIM®: 256450; 601820
Orphanet: ORPHA276525

Disease characteristics

Excerpted from the GeneReview: Familial Hyperinsulinism
Familial hyperinsulinism (referred to as FHI in this GeneReview) is characterized by hypoglycemia that ranges from severe neonatal-onset, difficult-to-manage disease to childhood-onset disease with mild symptoms and difficult-to-diagnose hypoglycemia. Neonatal-onset disease manifests within hours to two days after birth. Childhood-onset disease manifests during the first months or years of life. In the newborn period, presenting symptoms may be nonspecific, including seizures, hypotonia, poor feeding, and apnea. In severe cases, serum glucose concentrations are typically extremely low and thus easily recognized, whereas in milder cases, variable and mild hypoglycemia may make the diagnosis more difficult. Even within the same family, disease manifestations can range from mild to severe. Individuals with autosomal recessive familial hyperinsulinism, caused by pathogenic variants in either ABCC8 or KCNJ11 (FHI-KATP), tend to be large for gestational age and usually present with severe refractory hypoglycemia in the first 48 hours of life; affected infants usually respond only partially to diet or medical management (i.e., diazoxide therapy) and thus may require pancreatic resection. Individuals with autosomal dominant FHI-KATP tend to be appropriate for gestational age at birth, to present at approximately age one year (range: 2 days - 30 years), and to respond to diet and diazoxide therapy. Exceptions to both of these generalities have been reported. FHI-GCK, caused by pathogenic variants in GCK, may be much milder than FHI-KATP; however, some persons have severe, diazoxide-unresponsive hypoglycemia. FHI-HADH, caused by pathogenic variants in HADH, tends to be relatively mild, although severe cases have been reported. Individuals with FHI-HNF4A, caused by pathogenic variants in HNF4A, are typically born large for gestational age and have mild features that respond to diazoxide treatment. FHI-UCP2, caused by pathgoenic variants in UCP2, is a rare cause of diazoxide-responsive FH1. Hyperammonemia/hyperinsulinism (HA/HI) is associated with mild-to-moderate hyperammonemia and with relatively mild, late-onset hypoglycemia; most but not all affected individuals have pathogenic variants in GLUD1. [from GeneReviews]
Authors:
Benjamin Glaser   view full author information

Additional description

From GHR
Congenital hyperinsulinism is a condition that causes individuals to have abnormally high levels of insulin, which is a hormone that helps control blood sugar levels. People with this condition have frequent episodes of low blood sugar (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 sugar 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.  https://ghr.nlm.nih.gov/condition/congenital-hyperinsulinism

Recent clinical studies

Etiology

Gilis-Januszewska A, Piątkowski J, Skalniak A, Piwońska-Solska B, Nazim J, Pach D, Przybylik-Mazurek E, Sowa-Staszczak A, Starzyk J, Hubalewska-Dydejczyk A
Endokrynol Pol 2015;66(4):344-54. doi: 10.5603/EP.2015.0044. PMID: 26323472
Permutt MA, Chiu K, Ferrer J, Glaser B, Inoue H, Nestorowicz A, Stanley CA, Tanizawa Y
Recent Prog Horm Res 1998;53:201-16. PMID: 9769709
Nestorowicz A, Glaser B, Wilson BA, Shyng SL, Nichols CG, Stanley CA, Thornton PS, Permutt MA
Hum Mol Genet 1998 Jul;7(7):1119-28. PMID: 9618169
Glaser B, Chiu KC, Liu L, Anker R, Nestorowicz A, Cox NJ, Landau H, Kaiser N, Thornton PS, Stanley CA
Hum Mol Genet 1995 May;4(5):879-86. PMID: 7633448

Diagnosis

de las Heras J, Garin I, de Nanclares GP, Aguayo A, Rica I, Castaño L, Vela A
J Pediatr Endocrinol Metab 2010 Aug;23(8):827-30. PMID: 21073125
Taschenberger G, Mougey A, Shen S, Lester LB, LaFranchi S, Shyng SL
J Biol Chem 2002 May 10;277(19):17139-46. Epub 2002 Feb 26 doi: 10.1074/jbc.M200363200. PMID: 11867634
Partridge CJ, Beech DJ, Sivaprasadarao A
J Biol Chem 2001 Sep 21;276(38):35947-52. Epub 2001 Jul 16 doi: 10.1074/jbc.M104762200. PMID: 11457841
Sharma N, Crane A, Gonzalez G, Bryan J, Aguilar-Bryan L
Kidney Int 2000 Mar;57(3):803-8. doi: 10.1046/j.1523-1755.2000.00918.x. PMID: 10720932
Nestorowicz A, Glaser B, Wilson BA, Shyng SL, Nichols CG, Stanley CA, Thornton PS, Permutt MA
Hum Mol Genet 1998 Jul;7(7):1119-28. PMID: 9618169

Therapy

de las Heras J, Garin I, de Nanclares GP, Aguayo A, Rica I, Castaño L, Vela A
J Pediatr Endocrinol Metab 2010 Aug;23(8):827-30. PMID: 21073125
Cederblad F, Ewald U, Gustafsson J
Horm Res 1998;50(2):94-8. PMID: 9701703
Horev Z, Ipp M, Levey P, Daneman D
J Pediatr 1991 Nov;119(5):717-20. PMID: 1941376

Clinical prediction guides

Partridge CJ, Beech DJ, Sivaprasadarao A
J Biol Chem 2001 Sep 21;276(38):35947-52. Epub 2001 Jul 16 doi: 10.1074/jbc.M104762200. PMID: 11457841
Nestorowicz A, Inagaki N, Gonoi T, Schoor KP, Wilson BA, Glaser B, Landau H, Stanley CA, Thornton PS, Seino S, Permutt MA
Diabetes 1997 Nov;46(11):1743-8. PMID: 9356020
Glaser B, Chiu KC, Liu L, Anker R, Nestorowicz A, Cox NJ, Landau H, Kaiser N, Thornton PS, Stanley CA
Hum Mol Genet 1995 May;4(5):879-86. PMID: 7633448
Glaser B, Chiu KC, Anker R, Nestorowicz A, Landau H, Ben-Bassat H, Shlomai Z, Kaiser N, Thornton PS, Stanley CA
Nat Genet 1994 Jun;7(2):185-8. doi: 10.1038/ng0694-185. PMID: 7920639
Burman WJ, McDermott MT, Bornemann M
Arch Intern Med 1992 Oct;152(10):2125-7. PMID: 1358043

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