Congenital Hyperinsulinaemic Hypoglycaemia—A Review and Case Presentation

Abstract

Hyperinsulinaemic hypoglycaemia (HH) is the most common cause of persistent hypoglycaemia in infants and children with incidence estimated at 1 per 50,000 live births. Congenital hyperinsulinism (CHI) is symptomatic mostly in early infancy and the neonatal period. Symptoms range from ones that are unspecific, such as poor feeding, lethargy, irritability, apnoea and hypothermia, to more serious symptoms, such as seizures and coma. During clinical examination, newborns present cardiomyopathy and hepatomegaly. The diagnosis of CHI is based on plasma glucose levels <54 mg/dL with detectable serum insulin and C-peptide, accompanied by suppressed or low serum ketone bodies and free fatty acids. The gold standard in determining the form of HH is fluorine-18-dihydroxyphenyloalanine PET ((18)F-DOPA PET). The first-line treatment of CHI is diazoxide, although patients with homozygous or compound heterozygous recessive mutations responsible for diffuse forms of CHI remain resistant to this therapy. The second-line drug is the somatostatin analogue octreotide. Other therapeutic options include lanreotide, glucagon, acarbose, sirolimus and everolimus. Surgery is required in cases unresponsive to pharmacological treatment. Focal lesionectomy or near-total pancreatectomy is performed in focal and diffuse forms of CHI, respectively. To prove how difficult the diagnosis and management of CHI is, we present a case of a patient admitted to our hospital.

A Very Rare Case of Diabetes Mellitus Occurring in a Patient With Hyperinsulinism Hyperammonemia Syndrome

“… 7 , 8 Patients with HI/HA syndrome are usually responsive to diazoxide, which is an ATP-sensitive potassium (KATP) channel agonist. 1 , 5 , 9 , 10 There has been a report of variable phenotypes of this condition ranging from delayed presentation to spontaneous resolution of hypoglycemia but no report of T2DM developing in a patient with GLUD1 alteration. 11 There have been a few reports of patients with congenital hyperinsulinism who developed diabetes later in life, but this was due to an alteration in sulfonylurea receptor 1.…”

Congenital hyperinsulinism

“…Medfødt hyperinsulinisme debuterer vanligvis i nyfødtperioden, men hos om lag 10 % manifesterer tilstanden seg først i barne-og ungdomsårene (5). Sykdomsdebut med hypoglykemi opptrer oftest kort tid etter fødselen, og symptomene kan vaere uspesifikke og subtile (blekhet, hypotoni, slapphet) eller alvorlige og nevrologiske (apné, nedsatt bevissthet, sitringer, kramper, bevisstløshet, død) (4,6). Høy fødselsvekt kan vaere en indikasjon på medfødt hyperinsulinisme, men normal eller lav fødselsvekt utelukker ikke tilstanden (4).…”

“…Derfor skal det også tas prøve til genetisk undersøkelse av begge foreldrene. I dag er det kjent at mutasjoner i minst 15 gener kan forårsake medfødt hyperinsulinisme, og majoriteten av mutasjonene er recessive (se tabell 1 på tidsskriftet.no) (4,6). Mutasjonene medfører endret funksjon av korresponderende proteinprodukter i betacellene og kan klassifiseres som forstyrrelser av ionekanaler, metabolske enzymer eller transkripsjonsfaktorer, hvor førstnevnte ofte er mest alvorlig (figur 1).…”

“…Oversikt over de viktigste genene som kan forårsake medfødt hyperinsulinisme når de er mutert (4,6).…”

Genetic Heterogeneity Correlated with Phenotypic Variability in Congenital Hyperinsulinism Caused by Mutation in ABCC8 Gene Associated with Early‐Onset Persistent Neonatal Hypoglycemia

“…First-line drug treatment consists of oral diazoxide, glucagon, somatostatin analogues. In the focal CHI, the curative treatment involves the surgical excision of the focal lesion, while in the diffuse CHI, which does not respond to drug treatment, the symptoms can only be improved, through subtotal pancreatectomy, with the risk of complications, such as exocrine pancreatic insufficiency and diabetes mellitus [13][14][15].…”