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Hyperinsulinemic Hypoglycemia in Three Generations of a Family with Glucokinase Activating Mutation, c.295T>C (p.Trp99Arg)

Familial Hyperinsulinemic Hypoglycemia (FHH) is a very rare disease with heterogeneous clinical manifestations. There are only a few reports of heterozygous activating mutations of glucokinase (GCK) attributable to FHH, with no reports describing effects in the course in pregnancy with affected moth...

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Detalles Bibliográficos
Autores principales: Gilis-Januszewska, Aleksandra, Bogusławska, Anna, Kowalik, Artur, Rzepka, Ewelina, Soczówka, Karolina, Przybylik-Mazurek, Elwira, Głowa, Bogusław, Hubalewska-Dydejczyk, Alicja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535713/
https://www.ncbi.nlm.nih.gov/pubmed/34680961
http://dx.doi.org/10.3390/genes12101566
Descripción
Sumario:Familial Hyperinsulinemic Hypoglycemia (FHH) is a very rare disease with heterogeneous clinical manifestations. There are only a few reports of heterozygous activating mutations of glucokinase (GCK) attributable to FHH, with no reports describing effects in the course in pregnancy with affected mother/affected child. A large kindred with FHH and GCK:c.295T>C (p.Trp99Arg) pathogenic variant was identified in which four family members from three generations were affected. The clinical follow up in one clinical center lasted up to 30 years, with different times of diagnosis ranging from neonate period to adulthood. The severity of hypoglycemia was mild/severe and fasting was the trigger for hypoglycemia. Response to diazoxide varied from good, in the neonate, to moderate/poor, in childhood/adulthood; however, this was biased by poor compliance. Treatment with somatostatin analogues was discontinued due to side effects. Over time, patients developed clinical adaptation to very low glucose levels. During pregnancy, episodes of severe hypoglycemia in the first trimester were observed, which responded very well to steroids. The clinical course of the GCK:c.295T>C (p.Trp99Arg) mutation varied in the same family, with the development of clinical adaptation to very low glucose levels over time. Treatment with steroids might prevent hypoglycemia during pregnancy in an affected mother.