Long-Term Outcome and Treatment in Persistent and Transient Congenital Hyperinsulinism: A Finnish Population-Based Study

Abstract

Context The management of congenital hyperinsulinism (CHI) has improved. Objective To examine the treatment and long-term outcome of Finnish patients with persistent and transient CHI (P-CHI and T-CHI). Design A population-based retrospective study of CHI patient treated in 1972-2015. Patients 106 patients with P-CHI and 132 patients with T-CHI (altogether, 42 diagnosed before and 196 after year 2000) with a median follow-up times of 12.5 and 6.2 years, respectively. Main outcome measures Recovery, diabetes, pancreatic exocrine dysfunction, neurodevelopment. Results The overall incidence of CHI (n = 238) was 1:11 300 live births (1972-2015). In 2000-2015, the incidence of P-CHI (n = 69) was 1:13 500 and of T-CHI (n = 127) 1:7400 live births. In the 21 st century P-CHI group, hyperinsulinemic medication was initiated and normoglycemia achieved faster compared to earlier. Of the 74 medically treated P-CHI patients, 68% had discontinued medication. Thirteen (12%) P-CHI patients had partial pancreatic resection and 19 (18%) underwent near-total pancreatectomy. Of these, 0% and 84% developed diabetes and 23% and 58% had clinical pancreatic exocrine dysfunction, respectively. Mild neurological difficulties (21% vs 16%, respectively) and intellectual disability (9% vs 5%, respectively) were as common in the P-CHI and T-CHI groups. However, the 21 st century P-CHI patients had significantly more often normal neurodevelopment and significantly more infrequently diabetes and pancreatic exocrine dysfunction compared to those diagnosed earlier. Conclusions Our results demonstrated improved treatment and long-term outcome in the 21 st century P-CHI patients compared to earlier.

Increased referrals for congenital hyperinsulinism genetic testing in children with trisomy 21 reflects the high burden of non‐genetic risk factors in this group

“…In keeping with our findings, screening of the known genes identified an ABCC8 mutation in a single individual whilst the four mutation negative individuals had non-genetic risk factors for HI which could be attributed to the Down syndrome phenotype: extreme prematurity and cardiac insufficiency, IUGR, gastric surgery/fundoplication, and stress due to congenital heart defects (personal communication Huopio and Männistö). In two individuals the HI remitted before the age of 4 months.Genetic testing identified an ABCC8 mutation in one individualwith Down syndrome in our cohort and this, together with the finding of an ABCC8 mutation in an individual within the Finnish cohort, highlights the need to perform genetic testing in all individuals with persistent HI 20. Whilst a diagnosis of Down syndrome does not preclude co-incidental monogenic HI, our study suggests HI in Down syndrome is most likely to be due to non-genetic risk factors.…”

“…Genetic testing identified an ABCC8 mutation in one individual with Down syndrome in our cohort and this, together with the finding of an ABCC8 mutation in an individual within the Finnish cohort, highlights the need to perform genetic testing in all individuals with persistent HI 20 . Whilst a diagnosis of Down syndrome does not preclude co‐incidental monogenic HI, our study suggests HI in Down syndrome is most likely to be due to non‐genetic risk factors.…”

“…Interestingly, consanguinity was reported in one of these individuals, supporting the possibility of a recessively inherited monogenic etiology.Recently, a study of HI in Finland identified five cases with Down syndrome in a cohort of 238 individuals. The authors noted that this was a statistically significant increase compared to the population prevalence of Down syndrome 20. In keeping with our findings, screening of the known genes identified an ABCC8 mutation in a single individual whilst the four mutation negative individuals had non-genetic risk factors for HI which could be attributed to the Down syndrome phenotype: extreme prematurity and cardiac insufficiency, IUGR, gastric surgery/fundoplication, and stress due to congenital heart defects (personal communication Huopio and Männistö).…”

Congenital Hyperinsulinism: Current Laboratory-Based Approaches to the Genetic Diagnosis of a Heterogeneous Disease

“…Disease-causing variants in 10 genes have been reported to cause isolated, persistent HI ( Table 1 ). Loss-of-function variants in the ABCC8 and KCNJ11 genes, which encode the two subunits of the pancreatic beta-cell ATP-sensitive potassium (KATP) channel, are most common and reported in 30-66% of cases referred for genetic testing ( 3 , 4 , 26 , 27 ). A wide range of clinical severity is associated with KATP-HI with the functionally mildest variants causing transient disease which responds well to diazoxide treatment (the frontline drug for HI), whilst the most functionally severe variants cause diazoxide-unresponsive HI that persists throughout childhood ( 8 , 28 , 29 ).…”

Thai to - biến chứng và xử trí trẻ sau sinh

“…17 Trẻ thường nặng cân so với tuổi thai trong khi mẹ không có tiền sử tiểu đường thai kì, sau sinh trẻ thường hạ đường huyết sớm và kéo dài. 18 Cường insulin cũng liên quan đến các hội chứng khác như Beckwith-Wiedemann, Turner, Kabuki. 17…”