Monogenic hyperinsulinemic hypoglycemia: current insights into the pathogenesisand management

International Journal of Pediatric Endocrinology

Diva D De León¹  Katherine Lord² 

[1] Department of Pediatrics, Perelman School of Medicine at the University ofPennsylvania, Philadelphia, PA, USA;Division of Endocrinology and Diabetes, The Children’s Hospital ofPhiladelphia, 3615 Civic Center Boulevard, Abramson Research Center Room802A, Philadelphia, PA, 19104, USA

关键词: ¹⁸ F-DOPA PET;    K_ATP channel;    Insulin;    Neonatal hypoglycemia;    Beta-cell;   

Others  :  812644
DOI  :  10.1186/1687-9856-2013-3

 received in 2013-01-07, accepted in 2013-02-01,  发布年份 2013

【 摘 要 】

Hyperinsulinism (HI) is the leading cause of persistent hypoglycemia in children, which if unrecognized may lead to development delays and permanent neurologic damage. Prompt recognition and appropriate treatment of HI are essential to avoid these sequelae. Major advances have been made over the past two decades in understanding the molecular basis of hyperinsulinism and mutations in nine genes are currently known to cause HI. Inactivating K_ATP channel mutations cause the most common and severe type of HI, which occurs in both a focal and a diffuse form. Activating mutations of glutamate dehydrogenase (GDH) lead to hyperinsulinism/hyperammonemia syndrome, while activating mutations of glucokinase (GK), the “glucose sensor” of the beta cell, causes hyperinsulinism with a variable clinical phenotype. More recently identified genetic causes include mutations in the genes encoding short-chain 3-hydroxyacyl-CoA (SCHAD), uncoupling protein 2 (UCP2), hepatocyte nuclear factor 4-alpha (HNF-4α), hepatocyte nuclear factor 1-alpha (HNF-1α), and monocarboyxlate transporter 1 (MCT-1), which results in a very rare form of HI triggered by exercise. For a timely diagnosis, a critical sample and a glucagon stimulation test should be done when plasma glucose is < 50 mg/dL. A failure to respond to a trial of diazoxide, a K_ATP channel agonist, suggests a K_ATP defect, which frequently requires pancreatectomy. Surgery is palliative for children with diffuse K_ATPHI, but children with focal K_ATPHI are cured with a limited pancreatectomy. Therefore, distinguishing between diffuse and focal disease and localizing the focal lesion in the pancreas are crucial aspects of HI management. Since 2003, ¹⁸ F-DOPA PET scans have been used to differentiate diffuse and focal disease and localize focal lesions with higher sensitivity and specificity than more invasive interventional radiology techniques. Hyperinsulinism remains a challenging disorder, but recent advances in the understanding of its genetic basis and breakthroughs in management should lead to improved outcomes for these children.

【 授权许可】

   
2013 Lord and De León; licensee BioMed Central Ltd.

【 图 表 】

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