Hepatocyte Nuclear Factor 4α Gene Mutation Associated with Familial Neonatal Hyperinsulinism and Maturity-Onset Diabetes of the Young

Pingul, Mia M; Hughes, Nkecha; Wu, Anthony; Stanley, Charles A.; Gruppuso, Philip A.

doi:10.1016/j.jpeds.2011.01.003

Cited by 24 publications

(14 citation statements)

References 15 publications

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“…The MODY1 and MODY3 forms involve inactivating mutations of two related transcription factors, hepatocyte nuclear factor (HNF)-1␣ and HNF4␣ (1). Recently, HNF4A mutations associated with MODY1 were reported to cause macrosomia and hyperinsulinism that may persist for several months after birth before evolving to diabetes later in life (2)(3)(4). In contrast, HNF1A mutations associated with MODY3 have not been shown to lead to increased birth weight or neonatal hypoglycemia (2).…”

Section: Discussionmentioning

confidence: 99%

Novel Presentations of Congenital Hyperinsulinism due to Mutations in the MODY genes:HNF1AandHNF4A

Stanescu¹,

Hughes²,

Kaplan

et al. 2012

The Journal of Clinical Endocrinology & Metabolism

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154

113

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The first two cases demonstrate that mutations in HNF1A (MODY3) can cause hyperinsulinism early in life and diabetes later, similar to the phenotype recently reported for HNF4A (MODY1) mutations. Case 3 indicates that the effects of HNF4A mutations in infancy may extend beyond pancreatic β-cells to produce a disorder similar to glucose transporter 2 deficiency involving both liver glycogen metabolism and renal tubular transport.

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Section: Discussionmentioning

confidence: 99%

Novel Presentations of Congenital Hyperinsulinism due to Mutations in the MODY genes:HNF1AandHNF4A

Stanescu¹,

Hughes²,

Kaplan

et al. 2012

The Journal of Clinical Endocrinology & Metabolism

Self Cite

154

113

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“…Heterozygotic autosomal dominant mutations in HNF4A have been associated with maturity-onset diabetes of the young, type 1 (MODY1), but also with macrosomia and transient, as well as stable hyperinsulinaemic hypoglycaemia. Over 35% are de novo mutations [32][33][34].…”

Section: Hnf4a/hnf1amentioning

confidence: 99%

“…Heterozygotyczne mutacje genu HNF4A dziedziczone w sposób autosomalny dominujący powiązane zostały z cukrzycą MODY 1 (Maturity Onset Diabetes of the Young), ale także makrosomią i przejściową oraz trwałą hipoglikemią hiperinsulinemiczną. Ponad 35% wykrywanych mutacji to mutacje de novo [32][33][34].…”

Section: Prace Poglądoweunclassified

Nieinsulinowa hipoglikemia trzustkowa u dorosłych — przegląd genetyki

Gilis‐Januszewska

Piątkowski

Skalniak

et al. 2015

Endokrynologia Polska

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Hyperinsulinaemic hypoglycaemia (HH) is also classically referred to as "nesidioblastosis". Heterogeneous clinical manifestation of the disease causes risk of late diagnosis or even misdiagnosis. In infants and children, it can lead to serious and permanent damage to the central nervous system, which leads to the manifesting mental retardation. HH is characterised by unregulated insulin secretion from pancreatic β-cells. This effect has been correlated with nine genes: ABCC8, KCNJ11, GCK, GLUD-1, HADH1, SLC16A1, HNF4A, HNF1A, and UCP2. Mutations in these genes were found in approximately 48% of cases. The genetic background of the remaining cases is unknown. Understanding the genetic basis of familial hyperinsulinism has changed the early look at the disease. It has allowed for the differentiation of specific types of the disease. Depending on which of the nine disease-associated loci bears a pathogenic mutation, they differ in phenotype and pattern of inheritance. This review provides a brief overview of the genetic mechanisms of HH and its possible clinical presentations. StreszczenieHipogligemia hiperinsulinemiczna (HH) określana jest również terminem "nesidioblastoza". Różnorodna kliniczna manifestacja choroby powoduje ryzyko późnej diagnozy, a nawet braku rozpoznania. U niemowląt i dzieci nesidioblastoza prowadzić może do ciężkich i trwałych uszkodzeń centralnego systemu nerwowego, manifestujących się w postaci niedorozwoju umysłowego. Hipogligemia hiperinsulinemiczna charakteryzuje się nieuregulowanym wydzielaniem insuliny przez komórki β trzustki. Efekt ten powiązany został z dziewięcioma genami: ABCC8, KCNJ11, GCK, GLUD-1, HADH1, SLC16A1, HNF4A, HNF1A i UCP2. Mutacje występujące w wymienionych genach znajdowane są u 48% chorych. Genetyczne podłoże pozostałych przypadków pozostaje nieznane. Zrozumienie genetycznej przyczyny rodzinnej postaci hiperisnulinizmu zmieniło sposób, w jaki postrzegano chorobę. Pozwoliło na wyróżnienie poszczególnych jej typów. W zależność od tego, w którym z dziewięciu zasocjowanych z chorobą loci występuje patogenna mutacja, typy różnią się fenotypem i sposobem dziedziczenia. Praca stanowi krótki przegląd genetycznych patomechanizmów choroby obserwowanych w HH oraz ich możliwych prezentacji klinicznych. (Endokrynol Pol 2015; 66 (4): 344-354)

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“…[40] The phenotype of these patients is characterized by macrosomia and neonatal HH. [4142] The severity of HH in these patients varies from diet-controlled neonatal hypoglycemia to persistent HH requiring diazoxide treatment. In a recent series of 11 patients with HNF4A mutations, the HH was noted to range from three months to eight years with on-going need for diazoxide therapy.…”

Section: Aetiology Of Congenital Hyperinsulinism [Figure 1]mentioning

confidence: 99%

The molecular mechanisms, diagnosis and management of congenital hyperinsulinism

Senniappan

Arya

Hussain

2013

Indian J Endocr Metab

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Congenital hyperinsulinism (CHI) is the result of unregulated insulin secretion from the pancreatic β-cells leading to severe hypoglycaemia. In these patients it is important to make an accurate diagnosis and initiate the appropriate management so as to avoid hypoglycemic episodes and prevent the potentially associated complications like epilepsy, neurological impairment and cerebral palsy. At a genetic level abnormalities in eight different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) have been reported with CHI. Loss of function mutations in ABCC8/KCNJ11 lead to the most severe forms of CHI which are usually medically unresponsive. At a histological level there are two major subgroups, diffuse and focal, each with a different genetic etiology. The focal form is sporadic in inheritance and is localized to a small region of the pancreas whereas the diffuse form is inherited in an autosomal recessive (or dominant) manner. Imaging using a specialized positron emission tomography scan with the isotope fluroine-18 L-3, 4-dihydroxyphenyalanine (18F-DOPA-PET-CT) is used to accurately locate the focal lesion pre-operatively and if removed can cure the patient from hypoglycemia. Understanding the molecular mechanisms, the histological basis, improvements in imaging modalities and surgical techniques have all improved the management of patients with CHI.

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Hepatocyte Nuclear Factor 4α Gene Mutation Associated with Familial Neonatal Hyperinsulinism and Maturity-Onset Diabetes of the Young

Cited by 24 publications

References 15 publications

Novel Presentations of Congenital Hyperinsulinism due to Mutations in the MODY genes:HNF1AandHNF4A

Novel Presentations of Congenital Hyperinsulinism due to Mutations in the MODY genes:HNF1AandHNF4A

Nieinsulinowa hipoglikemia trzustkowa u dorosłych — przegląd genetyki

The molecular mechanisms, diagnosis and management of congenital hyperinsulinism

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