Hyperinsulinaemic Hypoglycaemia

Abstract

In the newborn and infancy periods HH can be either congenital or secondary to certain risk factors (such as intrauterine growth retardation) [ 4 ]. Congenital HH involves either defects in the genes ABCC8 and KCNJ11 (encoding for the 2 proteins SUR1 and KIR6.2 of the pancreatic β-cell K ATP channel, respectively), or abnormalities in the enzymes glucokinase, glutamate dehydrogenase and Short Chain Acyl-CoA Dehydrogenase (SCHAD) [ 5-10 ]. Mutations in ABCC8/KCNJ11 have been reported to account for 1/3 rd to 2/3 rd of the causes of congenital HH in large series of patients [ 11 , 12 ]. Mutations in GLUD1 are the second commonest cause, responsible for approximately 5 % of patients. Other known genes altogether account for less than 4 % of patient with congenital HH [ 11 , 12 ]. Loss of function mutations in the genes ABCC8 and KCNJ11 cause the most severe forms of HH, which is usually medically unresponsive. Histologically, HH can be classifi ed into 2 broad categories: diff use (aff ecting the whole pancreas) and focal (localised to a single region of pancreas) disease [ 13 ]. Recent development, fl ourine-18F 3,4-dihydroxyphenylalanine position emission tomography (18 F-DOPA-PET) scan, helps to diff erentiate focal from diff use disease and accurately localises the focal lesion preoperatively [ 14 ]. With the advent of 18 F-DOPA-PET scan and laparoscopic surgery, the clinical approach has changed dramatically.

A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome

“…In other syndromes that increase cytosolic calcium level in pancreatic β cells, patients experience a transient or permanent period of hyperinsulinaemic hypoglycemia. This hyperinsulinaemic hypoglycemia can be partially restored by an inhibitor for ATPsensitive potassium (K ATP ) channels or a calcium channel antagonist that prevents an increase in cytosolic calcium levels (45,46 reduces calcium leakage from the ER to cytosol, lowering cytosolic calcium level. The protective effect of dantrolene treatment on WFS1-deficient cells suggests that dysregulated cellular calcium homeostasis plays a role in the disease progression of Wolfram syndrome.…”

Severe Hyperinsulinemic Hypoglycemia in a Neonate: Response to Sirolimus Therapy

“…12 Focal lesions usually warrant surgical excision, whereas for therapy-resistant diffuse presentations the only treatment option available is subtotal or total pancreatectomy. 13 Definitive success rates are high for the former, but about one-third of patients remain hyperinsulinemic after subtotal pancreatectomy, many develop exocrine pancreatic insufficiency, and nearly all will develop diabetes by adolescence. 14 A recently published novel treatment option for HH of the newborn has been suggested including the immunosuppressant sirolimus, an mTOR inhibitor.…”

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“…Surgical management of this group of children would require near total pancreactectomy which has a high incidence of diabetes mellitus later on [10]. Several medications have been used for diffuse form of CHI, the first line being diazoxide usually being limited by the side effects [11]. Octreotide is used as the second line of treatment for diazoxide unresponsive forms of CHI [11].…”

“…Several medications have been used for diffuse form of CHI, the first line being diazoxide usually being limited by the side effects [11]. Octreotide is used as the second line of treatment for diazoxide unresponsive forms of CHI [11]. Octreotide is given 6-8 hrly SC injections.…”