Molecular Characterization and Management of Congenital Hyperinsulinism: A Tertiary Centre Experience

Background: There is limited data from India regarding medical management of congenital hyperinsulinism (CHI). Objective: To study the molecular diagnosis, medical management and outcomes of children with CHI. Study design: Ambispective. Participants: Children with CHI admitted in from December, 2011 till March, 2020 at a tertiary care referral hospital. Outcomes: Clinical and genetic profile, treatment, and response Results: 42 children with a median age of 3 days (range 1 day to 6 years) were enrolled, of which 23 (54.7%) were diazoxideresponsive. Mutations were identified in 28 out of 41 (68.2%) patients. The commonest gene affected was ABCC8 in 22 patients. The pathogenic variant c.331G>A in ABCC8 gene was identified in 6 unrelated cases from one community. Good response to daily octreotide was seen in 13 of the 19 (68.4%) diazoxide-unresponsive patients. Monthly long-acting octreotide was initiated and daily octreotide could be stopped or tapered in 9 patients. Sirolimus was tried with variable response in 6 patients but was discontinued in 5 due to adverse effects. Four patients had focal CHI, of which one underwent partial pancreatic resection. The disease severity reduced with age and neurodevelopment was good in the patients with identifiable genetic defects who were optimally managed. Conclusions: Medical management of CHI is effective, if compliance can be ensured, with good quality of life and neurological outcomes.

Gilbert syndrome in a young boy with thalassemia trait: a rare association

Gilbert syndrome (GS) is a mild benign disease characterized by asymptomatic unconjugated hyperbilirubinemia in absence of liver disease or hemolysis. This is the most common disorder associated with bilirubin metabolism with autosomal recessive inheritance. It usually precipitates during episodes of dehydration, fasting or stress like intercurrent illnesses. Here, we are reporting a case of Gilbert syndrome in 12 yrs old boy with thalassemia trait who presented with history of persistent jaundice for last 10 months. He had disproportionately higher concentration of unconjugated bilirubin which cannot be attributed to either disorder alone. Authors considered the possibility of Gilbert syndrome after ruling out hemolytic anemia. Though genetic testing is considered to be gold standard for diagnosis of Gilbert syndrome but availability is an issue. Calorie restriction test and nicotinic acid provocation test has been used to confirm GS too. Rifampicin test, another simple test which has been described in literature though not widely used in diagnosis. It has high sensitivity and specificity too. Authors had performed rifampicin test in our index case to confirm the diagnosis of GS. Here, authors wish to highlight the patients with both GS and thalassemia trait has higher bilirubin concentrations and is more likely to be icteric than either defect alone.

Bronchoalveolar lavage for etiological diagnosis of childhood pneumonia

Background: Pneumonia is the most common cause of childhood morbidity and mortality in age group less than 5 years. Identification of causative organism is a real challenge in these children though many of them are responding to the first line antibiotics therapy. Isolation of the organism is of paramount importance those who fails to respond to first line therapy. The objective of this study was to determine the relative efficacy of Bronchoalveolar Lavage (BAL) over blood culture in finding out causative organisms of childhood non responder community acquired pneumonia and to study antibiotic-sensitivity pattern of causative organisms. 'Methods: BAL and blood culture was performed in 17 patients of age 2 months to 5 years with pneumonia or severe pneumonia. Lavage fluid was cultured and growth of organism 10000CFU/ml was considered positive. Blood culture was taken on the same day. Antibiotic sensitivity was tested.Results: BAL isolated the organism in 82.35% (n=14) cases out of 17 patients and in 11.76% (n=2) by blood culture (p=0.002). Streptococcus pneumoniae was the most common organism isolated (58.82% (n=10)), followed by K. pneumoniae (23.53% (n=4)). Antibiotic therapy was changed in 58.82% (n=10) cases according on culture report. Transient rise in temperature, tachycardia and tachypnea was noted after procedure but no major complication was associated with BAL.Conclusions: BAL fluid culture in childhood pneumonia has high diagnostic value and better efficacy over blood culture in isolating causative organism without increased risk of complication and decreases unwanted exposure to empiric antibiotic in children with community acquired pneumonia who did not respond to initial 1st line therapy.

Distal Renal Tubular Acidosis Associated with Celiac Disease and Thyroiditis.

Background: Association of distal renal tubular acidosis (RTA) with autoimmune diseases is extremely rare in children.Case Characteristics: 12-year-old girl with distal RTA. Despite resolution of acidosis on bicarbonate, she continued to have poor growth and delayed puberty. Investigations revealed autoimmune thyroiditis and celiac disease. Outcome: Levothyroxine and gluten-free diet were initiated. Child gained height and weight and had onset of puberty after gluten withdrawal. Messages: Distal RTA in children may rarely be of autoimmune etiology.

Hyperinsulinemic Hypoglycemia of Infancy due to Novel HADH Mutation in Two Siblings.

Background: Hyperinsulinemia is the commonest cause of persistent hypoglycemia in infancy. Inactivating mutations in the genes ABCC8 and KCNJ11 are the commonest cause. Mutation in the HADH gene, which encodes the short-chain-L-3-hydroxyacyl-CoA dehydrogenase, is a rare cause. Case characteristics: Two Indian sisters who presented with hyperinsulinemic hypoglycemia of infancy. Observation/Intervention: A novel homozygous missense mutation in the HADH gene was identified in both the sisters, while the parents were found to be heterozygous carriers. Outcome: Establishment of molecular diagnosis, optimization of therapy and counseling of parents regarding risk of recurrence in future pregnancy. Messages: HADH mutations are rare causes of hypoglycemia and can be mitigated with diazoxide and appropriate dietary therapy if identified early.

Surreptitious Insulin Overdosing in Adolescents with Type 1 Diabetes.

Background: Hypoglycemia in children and adolescents with type 1 diabetes has diverse etiologies. Case Characteristics: We report recurrent hypoglycemia in three children with type 1 diabetes because of insulin overdose. Intervention: Hospitalization and counseling by treating team and psychologist helped in resolving the recurrent hypoglycemia. Outcome: Improvement in glycemic control was achieved. Message: Adolescents with type 1 diabetes may take extra insulin to consume more carbohydrates, or to seek attention. Parents should share the responsibility of care of adolescents during transition phase for better glycemic control.

Pheochromocytoma Presenting as Diabetes Insipidus.

Background: Pheochromocytomas are catecholamine producing tumors that classically present with the triad of sweating, palpitations and headache. Case characteristics: 9- year-old boy whose only presenting complaints were polyuria and polydipsia for 2 years. Observation: Routine measurement of blood pressure detected mild hypertension, and subsequent investigations revealed bilateral pheochromocytoma. Outcome: Surgical removal of the tumors resulted in complete resolution of polyuria and polydipsia. Message: The case highlights the importance of measuring BP for children as part of physical examination.