Congenital Hyperinsulinism Caused by Mutations in ABCC8 Gene Associated with Early-Onset Neonatal Hypoglycemia: Genetic Heterogeneity Correlated with Phenotypic Variability

被引:2
作者
Butnariu, Lacramioara Ionela [1 ]
Bizim, Delia Andreia [2 ]
Paduraru, Gabriela [3 ]
Paduraru, Luminita [4 ]
Moisa, Stefana Maria [3 ]
Popa, Setalia [1 ]
Gimiga, Nicoleta [3 ]
Ghiga, Gabriela [3 ]
Badescu, Minerva Codruta [5 ]
Lupu, Ancuta [3 ]
Vasiliu, Ioana [6 ]
Trandafir, Laura Mihaela [3 ]
机构
[1] Grigore T Popa Univ Med & Pharm, Fac Med, Dept Med Genet, Iasi 700115, Romania
[2] St Marys Emergency Children Hosp, Dept Diabet, Iasi 700309, Romania
[3] Grigore T Popa Univ Med & Pharm, Fac Med, Dept Mother & Child, Iasi 700115, Romania
[4] Grigore T Popa Univ & Pharm, Fac Med, Dept Mother & Child, Div Neonatol, Iasi 700115, Romania
[5] Grigore T Popa Univ Med & Pharm, Dept Internal Med, 16 Univ St, Iasi 700115, Romania
[6] Grigore T Popa Univ Med & Pharm, Dept Morphofunct Sci 2, Iasi 700115, Romania
关键词
hyperinsulinemic hypoglycemia; ABCC8; gene; mutation; ATP-sensitive potassium channel; genetic heterogeneity; phenotypic variability; DIAGNOSIS; GENOTYPE; CHILDREN;
D O I
10.3390/ijms25105533
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (K-ATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset HH caused by ABCC8 gene mutations. In the first patient, who presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330-1)del] that correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of the focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[F-18]fluoro-L-phenylalanine) positron emission tomography/computed tomography (PET/CT) was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.
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页数:13
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