Heterozygous Insulin Receptor (INSR) Mutation Associated with Neonatal Hyperinsulinemic Hypoglycaemia and Familial Diabetes Mellitus: Case Series
| Autor: | Sarah Ehtisham, Syed Haris Ahmed, Senthil Senniappan, Nicola Foulds, Sarah E. Flanagan, Jayne A L Houghton, Aashish Sethi, Mohammed Didi, Kevin Colclough |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Proband medicine.medical_specialty Endocrinology Diabetes and Metabolism Case Report 030209 endocrinology & metabolism lcsh:Diseases of the endocrine glands. Clinical endocrinology congenital hyperinsulinism 03 medical and health sciences INSR mutation familial diabetes mellitus 0302 clinical medicine Endocrinology Insulin resistance Internal medicine Diabetes mellitus medicine Diazoxide Missense mutation lcsh:RC648-665 business.industry lcsh:RJ1-570 nutritional and metabolic diseases lcsh:Pediatrics medicine.disease Gestational diabetes 030104 developmental biology Pediatrics Perinatology and Child Health Congenital hyperinsulinism Small for gestational age business neonatal hyperinsulinemic hypoglycemia hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Journal of Clinical Research in Pediatric Endocrinology JCRPE, Vol 12, Iss 4, Pp 420-426 (2020) |
| ISSN: | 1308-5735 1308-5727 |
| DOI: | 10.4274/jcrpe.galenos.2019.2019.0106 |
| Popis: | Mutations in the insulin receptor (INSR) gene are associated with insulin resistance and hyperglycaemia. Various autosomal dominant heterozygous INSR mutations leading to hyperinsulinemic hypoglycaemia (HH) have been described in adults and children (more than 3 years of age) but not in the neonatal period. Family 1: A small for gestational age (SGA) child born to a mother with gestational diabetes presented with persistent hypoglycaemia, was diagnosed with HH and responded well to diazoxide treatment. Diazoxide was gradually weaned and discontinued by 8 months of age. Later, the younger sibling had a similar course of illness. On genetic analysis a heterozygous INSR missense variant p.(Met1180Lys) was found in the siblings, mother and grandfather but not in the father. Family 2: A twin preterm and SGA baby presented with persistent hypoglycaemia, which was confirmed as HH. He responded to diazoxide, which was subsequently discontinued by 10 weeks of life. Genetic analysis revealed a novel heterozygous INSR missense variant p.(Arg1119Gln) in the affected twin and the mother. Family 3: An SGA child presented with diazoxide responsive HH. Diazoxide was gradually weaned and discontinued by 9 weeks of age. Genetic analysis revealed a novel heterozygous INSR p.(Arg1191Gln) variant in the proband and her father. We report, for the first time, an association of INSR mutation with neonatal HH responsive to diazoxide therapy that resolved subsequently. Our case series emphasizes the need for genetic analysis and long-term follow up of these patients. |
| Databáze: | OpenAIRE |
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