Browsing by Author "Hussain, Khalid (26643177200)"

Persistent hypoglycaemia in newborns and infants is most commonly caused by congenital hyperinsulinism (CHI). Most CHI studies report outcomes in children from both consanguineous and non-consanguineous families which can affect the phenotype-genotype analysis. The aim of this study was to analyze characteristics of patients with CHI in 21 non-consanguineous families from Serbia. This retrospective cohort study included a total of 21 patients with CHI treated in the Mother and Child Healthcare Institute of Serbia during the past 20 years. The prevalence of macrosomia at birth was very low in our cohort (4.8%). Median age at presentation was 6 days, with seizures as the presenting symptom in 76% of patients. Only four patients (19%) were diazoxide unresponsive, and eventually underwent pancreatectomy. Genetic testing was performed in 15 patients and genetic diagnosis was confirmed in 60%, with all patients being heterozygous for detected mutations. The ABCC8 gene mutations were detected in 55.6%, GLUD1 in three patients (33.3%) with HIHA syndrome and one patient had HNF4A gene mutation and unusual prolonged hyperglycaemia lasting 6 days after diazoxide cessation. Neurodevelopmental deficits persisted in 33% of patients. Conclusion: This is the first study regarding CHI patients in Serbia. It suggests that in countries with low consanguinity rate, majority of CHI patients are diazoxide responsive. The most common mutations were heterozygous ABCC8, followed by GLUD1 and HNF4A mutations, suggesting the potential benefit of population-tailored genetic analysis approach, targeting the mutations causing CHI via dominant inheritance model in regions with low consanguinity rates.What is Known:• Persistent hypoglycaemia during infancy and early childhood is most commonly caused by congenital hyperinsulinism (CHI).• Consanguinity is a very important factor regarding the genetics and phenotype of CHI, increasing the risk of autosomal recessive genetic disorders, including the severe, diazoxide-unresponsive forms caused by recessive inactivating mutations in ABCC8 and KCNJ11.What is New:• Results of the present study which included CHI patients from 21 non-consanguineous families suggest that in countries with low consanguinity rates, majority of CHI patients can be diazoxide responsive, with most common mutations being heterozygous ABCC8, followed by GLUD1 and HNF4A mutations.• Unusually prolonged hyperglycaemic reaction to diazoxide treatment in a patient with HNF4A mutation was also described in the present study. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is considered as the second most common type of hereditary HI. Correlation of genotype and phenotype in HI/HA syndrome has been described in several studies. We present three Serbian patients with HI/HA syndrome with emphasis on a possible correlation between genotype and clinical manifestations. Patient 1 was heterozygous for a de novo mutation p.S445L in the GLUD1 gene, while patients 2 and 3 (son and mother) both carry the p.R221C mutation. Early onset of hypoglycaemia with generalized seizures was recorded in infancy in all three patients. The two male patients had mild developmental delay, while the female patient presented with epilepsy. Analysis of Serbian patients with HI/HA syndrome confirms the association of p.S445L and p.R221C mutations with hypoglycaemic seizures noted within the first three months of life and with subsequent risk for cognitive impairment and/or epilepsy. © Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is considered as the second most common type of hereditary HI. Correlation of genotype and phenotype in HI/HA syndrome has been described in several studies. We present three Serbian patients with HI/HA syndrome with emphasis on a possible correlation between genotype and clinical manifestations. Patient 1 was heterozygous for a de novo mutation p.S445L in the GLUD1 gene, while patients 2 and 3 (son and mother) both carry the p.R221C mutation. Early onset of hypoglycaemia with generalized seizures was recorded in infancy in all three patients. The two male patients had mild developmental delay, while the female patient presented with epilepsy. Analysis of Serbian patients with HI/HA syndrome confirms the association of p.S445L and p.R221C mutations with hypoglycaemic seizures noted within the first three months of life and with subsequent risk for cognitive impairment and/or epilepsy. © Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing.

Background: Postprandial hyperinsulinemic hypoglycemia (PHH) is an increasingly recognized complication of gastric bypass surgery in obese adults, distinct from the "dumping syndrome". Case presentation: Upon birth, primary repair of esophageal atresia was performed, and at the age of 14 months definite esophageal reconstruction was performed. At the age of 3 years, recurrent brief episodes of symptomatic hypoglycemia started. At the age of 5.7 years the girl was admitted to our clinic and investigations indicated hyperinsulinemic hypoglycemia. Oral glucose tolerance test (OGTT) and continuous glucose monitoring results revealed frequent postprandial hypoglycemic events, which were always preceded by early postprandial hyperglycemia. It was concluded that the patient had PHH caused by a delayed and hyperinsulinemic response to carbohydrate intake as a result of esophagogastric surgery. Treatment with acarbose was titrated using flash glucose monitoring, which resulted in satisfactory glucose regulation. Conclusions: This is the first described case of a child with PHH following esophageal reconstruction. © 2017 Walter de Gruyter GmbH, Berlin/Boston.

Background: Postprandial hyperinsulinemic hypoglycemia (PHH) is an increasingly recognized complication of gastric bypass surgery in obese adults, distinct from the "dumping syndrome". Case presentation: Upon birth, primary repair of esophageal atresia was performed, and at the age of 14 months definite esophageal reconstruction was performed. At the age of 3 years, recurrent brief episodes of symptomatic hypoglycemia started. At the age of 5.7 years the girl was admitted to our clinic and investigations indicated hyperinsulinemic hypoglycemia. Oral glucose tolerance test (OGTT) and continuous glucose monitoring results revealed frequent postprandial hypoglycemic events, which were always preceded by early postprandial hyperglycemia. It was concluded that the patient had PHH caused by a delayed and hyperinsulinemic response to carbohydrate intake as a result of esophagogastric surgery. Treatment with acarbose was titrated using flash glucose monitoring, which resulted in satisfactory glucose regulation. Conclusions: This is the first described case of a child with PHH following esophageal reconstruction. © 2017 Walter de Gruyter GmbH, Berlin/Boston.