OBJECTIVES: Long-term clinical follow-up and mutation analysis were performed in 27 Chinese congenital hyperinsulinism patients. METHOD: 27 hypoglycemia patients were diagnosed with CHI within 2 years of age. The long-term clinical outcome was analyzed and mutation analysis of 5 hyperinsulinism candidate genes was performed. RESULTS: The median onset age of hypoglycemia in the patients was 60 days; 11 patients showed hypoglycemic symptoms in the neonatal stage, and hypoglycemia in most of the patients was first expressed as a seizure. Blood was collected during the hypoglycemic episode and insulin levels were significantly elevated. ABCC8, KCNJ11, GCK, HNF4a and GLUD1 genes were screened for mutation analysis. 14 mutations in ABCC8 or KCNJ11 genes in 12 cases were identified (44%). 57% (8/14) of the mutations have not been reported before. 83% (10/12) of the patients have a monoallelic mutation. 58% of these 12 patients were predicted to be focal. 73% of the patients without KATP channel mutations were sensitive to diazoxide. 26 patients were followed over a period of 1-13 years. 50% of all 27 patients showed brain impairment. CONCLUSIONS: Chinese CHI patients are similar to other ethnic groups in terms of prevalence of KATP-HI, onset age, severity of hypoglycemia and treatment. Mutations in ABCC8 and KCNJ11 are common causes of CHI in Chinese patients. Mutation analysis showed more novel and monoallele mutations in KATP genes.
OBJECTIVES: Long-term clinical follow-up and mutation analysis were performed in 27 Chinese congenital hyperinsulinismpatients. METHOD: 27 hypoglycemiapatients were diagnosed with CHI within 2 years of age. The long-term clinical outcome was analyzed and mutation analysis of 5 hyperinsulinism candidate genes was performed. RESULTS: The median onset age of hypoglycemia in the patients was 60 days; 11 patients showed hypoglycemic symptoms in the neonatal stage, and hypoglycemia in most of the patients was first expressed as a seizure. Blood was collected during the hypoglycemic episode and insulin levels were significantly elevated. ABCC8, KCNJ11, GCK, HNF4a and GLUD1 genes were screened for mutation analysis. 14 mutations in ABCC8 or KCNJ11 genes in 12 cases were identified (44%). 57% (8/14) of the mutations have not been reported before. 83% (10/12) of the patients have a monoallelic mutation. 58% of these 12 patients were predicted to be focal. 73% of the patients without KATP channel mutations were sensitive to diazoxide. 26 patients were followed over a period of 1-13 years. 50% of all 27 patients showed brain impairment. CONCLUSIONS: Chinese CHI patients are similar to other ethnic groups in terms of prevalence of KATP-HI, onset age, severity of hypoglycemia and treatment. Mutations in ABCC8 and KCNJ11 are common causes of CHI in Chinese patients. Mutation analysis showed more novel and monoallele mutations in KATP genes.
Authors: Chris Worth; Laila Al Hashmi; Daphne Yau; Maria Salomon-Estebanez; Diego Perez Ruiz; Caroline Hall; Elaine O'Shea; Helen Stokes; Peter Foster; Sarah E Flanagan; Karen E Cosgrove; Mark J Dunne; Indraneel Banerjee Journal: Orphanet J Rare Dis Date: 2020-06-24 Impact factor: 4.123