An extremely rare case of endophthalmitis in an infant with congenital tuberculosis.

Congenital tuberculosis (CTB) is the transmission of Mycobacterium tuberculosis infection from mother to infant during the intrauterine period or delivery. An 82-day-old infant presented to Nilratan Sircar Medical College and Hospital, Kolkata, with a history of persistent fever from Day 15 of age. Over the course of more than 2 months, there were pneumonia, hepatosplenomegaly and endophthalmitis which were unresponsive to a range of antibiotics, and there had been several admissions to local hospitals. On this admission, his chest radiograph and contrast-enhanced computed tomography (CECT) of the thorax demonstrated bilateral nodules and enlarged mediastinal lymph nodes. Ultrasound and CECT of the abdomen demonstrated hepatosplenomegaly with multiple hypodense enhancing lesions. GeneXpert of a gastric lavage on Day 2 of this admission detected M. tuberculosis without rifampicin resistance. The infant was diagnosed with tuberculosis (TB) complicated by caseating hepatic granulomas, which fulfilled Cantwell's diagnostic criteria for CTB. Magnetic resonance imaging of the orbit demonstrated focal heterogeneous lesions involving the anterior portion of the left ocular bulb and vitreous, suggesting panophthalmitis, which was unresponsive to intravitreal antibiotics. Following commencement of standard anti-TB therapy from Day 90 of life, there was clinical and radiological recovery of endophthalmitis. The mother had a cachectic appearance owing to weight loss, and she had attended only one antenatal appointment. She had a positive acid-fast bacilli sputum stain but was unwilling to allow a genital tract smear. In the spectrum of CTB, TB panophthalmitis is an extremely rare presentation, and, as far as we are aware, it has not been reported in a child.Abbreviations: AFB: acid-fast bacilli; ATT: anti-tuberculous therapy; CTB: congenital tuberculosis; CECT: contrast-enhanced computed tomography; CSF: cerebrospinal fluid; ESR: erythrocyte sedimentation rate; HIV: human immunodeficiency virus; TB: tuberculosis; MRI: magnetic resonance imaging; USG: ultrasonogram.

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 diazoxide-responsive. 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.

Life-threatening Hypercalcemia as the First Manifestation of Acute Lymphoblastic Leukemia.

Hypercalcemia of malignancy, usually reported in adults in advanced stages, is rare in children. A 4-year-old boy presented with intermittent episodes of severe hypercalcemia, which improved with intravenous hydration therapy, furosemide and bisphosphonates as the initial manifestation of occult acute lymphoblastic leukemia. Pediatricians should rule out hematological malignancy in patients with severe hypercalcemia.

Congenital Hyperinsulinemic Hypoglycemia and Hyperammonemia due to Pathogenic Variants in GLUD1.

Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disorder, characterized by dysregulated insulin secretion. Pathogenic variants in at least twelve different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A, HNF1A, UCP2, TRMT10A HK1, and PGM1) are known to cause CHI. Pathogenic variants in the GLUD1 gene, which encodes the enzyme glutamate dehydrogenase (GDH), account for 5% of the cases of congenital hyperinsulinemic hypoglycemia. Pathogenic variants in GLUD1 typically present in late infancy, are diet and/or diazoxide-responsive and cause protein-induced hyperinsulinemic hypoglycemia as insulin secretion is triggered by allosteric activation of GDH by leucine. The authors are presenting three unrelated Indian children, who manifested with fasting as well as dietary protein induced hypoglycemia in late infancy, and were diagnosed to have hyperinsulinemic hyperammonemic hypoglycemia due to pathogenic variants in GLUD1. Although the hypoglycemia responded to diazoxide, delayed diagnosis and irregular treatment had resulted in neurological problems in two of the three children. Early identification, appropriate dietary modifications and regular treatment with diazoxide can prevent adverse neurological outcome.