Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India

Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Majority of our patients (89%) presented within 6 months of age. The most common clinical manifestations observed were recurrent pneumonia (66%), failure to thrive (60%), chronic diarrhea (35%), gastrointestinal infection (21%), and oral candidiasis (21%). Hematopoietic Stem Cell Transplantation (HSCT) is the only curative therapy available for treating these patients. Four patients underwent HSCT in our cohort but had a poor survival outcome. Lymphopenia (absolute lymphocyte counts/μL <2,500) was noted in 63% of the patients. Based on immunophenotypic pattern, majority of the cases were T−B− SCID (39%) followed by T−B+ SCID (28%). MHC class II deficiency accounted for 10.5% of our patient group. A total of 49 patients were molecularly characterized in this study and 32 novel variants were identified in our cohort. The spectrum of genetic defects in our cohort revealed a wide genetic heterogeneity with the major genetic cause being RAG1/2 gene defect (n = 12) followed by IL2RG (n = 9) and JAK3 defects (n = 9). Rare forms of SCID like Purine nucleoside phosphorylase (PNP) deficiency, reticular dysgenesis, DNA-Protein Kinase (DNA-PKcs) deficiency, six cases of MHC class II deficiency and two ZAP70 deficiency were also identified in our cohort. Fourteen percent of the defects still remained uncharacterized despite the application of next generation sequencing. With the exception of MHC class II deficiency and ZAP70 deficiency, all SCID patients had extremely low T cell receptor excision (TRECs) (<18 copies/μL)

Laparoscopic excision of hepatoduodenal ligament cyst

Hepatoduodenal ligament cysts are rare. These may be confused with hepatic cysts even on advanced investigative modalities like Computerized tomography scanning or Magnetic Resonance Imaging. Diagnosis is often an intraoperative surprise. Laparoscopic treatment of such hepatoduodenal cysts is not described in available medical literature. We report one such case treated laparoscopicall

Laparoscopic adrenalectomy for large tumours: Single team experience

Background: Laparoscopic adrenalectomy (LA) has become the procedure of choice to treat benign functioning and non-functioning adrenal tumours. With improving experience, large adrenal tumours (> 5 cm) are being successfully tackled by laparoscopy. This study aims to present our single unit experience of LA performed for large adrenal masses. Materials and Methods: Forty-six laparoscopic adrenalectomies performed for large adrenal lesions more than 5 cm during the period 2001 to 2010 were reviewed. Results: A total of 46 adrenalectomies were done in 42 patients. The mean tumour size was 7.03 cm (5-15 cm). Fourteen patients had tumour size more than 8 cm. The lesions were localised on the right side in 17 patients and on the left side in 21 patients with bilateral tumours in 4 patients. Functioning tumours were present in 32 of the 46 patients. The average blood loss was 112 ml (range 20-400 ml) with the mean operating time being 144 min (range 45 to 270 min). Five patients required conversion to open procedure. Three of the 46 patients (6.52%) on final histology had malignant tumours. Conclusion: LA is safe and feasible for large adrenal lesions. Mere size should not be considered as a contraindication to laparoscopic approach in large adrenal masses. Graded approach, good preoperative assessment, team work and adherence to anatomical and surgical principles are the key to success

Laparoscopic adrenalectomy: Gaining experience by graded approach

INTRODUCTION: Laparoscopic adrenalectomy (LA) has become a gold standard in management of most of the adrenal disorders. Though report on the first laparoscopic adrenalectomy dates back to 1992, there is no series of LA reported from India. Starting Feb 2001, a graded approach to LA was undertaken in our center. Till March 2006, a total of 34 laparoscopic adrenalectomies were performed with success. MATERIALS AND METHODS: The endocrinology department primarily evaluated all patients. Patients were divided into Group A - unilateral LA and Group B - bilateral LA (BLA). The indications in Group A were pheochromocytoma (n=7), Conn′s syndrome (n=3), Cushing′s adenoma (n=2), incidentaloma (n=2); and in Group B, Cushing′s disease (CD) following failed trans-sphenoid pituitary surgery (n = 8); ectopic ACTH- producing Cushing′s syndrome (n=1) and congenital adrenal hyperplasia (CAH) (n=1). The lateral transabdominal route was used. RESULTS: The age group varied from 12-54 years, with mean age of 28.21 years. Average duration of surgery in Group A was 166.43 min (40-270 min) and 190 min (150- 310 min) in Group B. Average blood loss was 136.93 cc (20-400 cc) in Group A and 92.5 cc (40-260 cc) in Group B. There was one conversion in each group. Mean duration of surgical stay was 1.8 days (1-3 days) in Group A and 2.6 days (2-4 days) in Group B. All the patients in both groups were cured of their illness. Three patients in Group B developed Nelson′s syndrome. The mean follow up was of 24.16 months (4-61 months). CONCLUSION: LA though technically demanding, is feasible and safe. Graded approach to LA is the key to success

Coexistence of pheochromocytoma/praganglioma and renal artery stenosis

Renal artery stenosis (RAS) often coexists with pheochromocytoma (Pheo)/paraganglioma (PGL) and often alters the management of patients with Pheo/PGL. We have studied the prevalence of RAS in our Pheo/PGL patients. The study included 70 consecutive, histopathologically proven Pheo/PGL patients from a tertiary health care center. In 60 patients, tumors were limited to adrenal glands (54 unilateral and 6 bilateral) while other 10 patients had extra-adrenal abdominal tumors. Five patients had RAS with an overall prevalence of 14%. Only two out of 60 patients with Pheo had RAS with a low prevalence of 3.3% while three out of 10 patients with extra-adrenal abdominal PGL had RAS with a prevalence of 30%. To conclude, RAS commonly coexists with Pheo/PGL, more often with extra-adrenal PGL

Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India

Major histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th) cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy available for treating these patients. This is the first report from India wherein we describe the clinical, immunological, and molecular findings in five patients with MHC class II deficiency. Our patients presented with recurrent lower respiratory tract infection as the most common clinical presentation within their first year of life and had a complete absence of human leukocyte antigen-antigen D-related (HLA-DR) expression on B cells and monocytes. Molecular characterization revealed novel mutations in RFAXP, RFX5, and CIITA genes. Despite genetic heterogeneity, these patients were clinically indistinguishable. Two patients underwent HSCT but had a poor survival outcome. Detectable level of T cell receptor excision circles (TRECs) were measured in our patients, highlighting that this form of PID may be missed by TREC-based newborn screening program for severe combined immunodeficiency

Clinical, Immunological, and Molecular Findings in Four Cases of B Cell Expansion With NF-κB and T Cell Anergy Disease for the First Time From India

B cell expansion with NF-κB and T cell anergy (BENTA) is a rare primary immunodeficiency disorder caused by mutations in the CARD11 gene and results in constitutive NF-κB activation in B and T cells. Affected patients present with polyclonal expansion of B cells at an early age with splenomegaly, lymphadenopathy, and mild autoimmunity. Here, we discuss four BENTA cases with unusual clinical manifestations not previously reported. All patients showed previously reported gain-of-function mutations (G123S, G123D, and C49Y) in the CARD11 gene. Severe autoimmune manifestations were noted for the first time in all our patients

Poliovirus Excretion in Children with Primary Immunodeficiency Disorders, India

Prolonged excretion of poliovirus can occur in immunodeficient patients who receive oral polio vaccine, which may lead to propagation of highly divergent vaccine-derived polioviruses (VDPVs), posing a concern for global polio eradication. This study aimed to estimate the proportion of primary immunodeficient children with enterovirus infection and to identify the long-term polio/nonpolio enterovirus excreters in a tertiary care unit in Mumbai, India. During September 2014–April 2017, 151 patients received diagnoses of primary immunodeficiency (PID). We isolated 8 enteroviruses (3 polioviruses and 5 nonpolio enteroviruses) in cell culture of 105 fecal samples collected from 42 patients. Only 1 patient with severe combined immunodeficiency was identified as a long-term VDPV3 excreter (for 2 years after identification of infection). Our results show that the risk of enterovirus excretion among children in India with PID is low; however, systematic screening is necessary to identify long-term poliovirus excreters until the use of oral polio vaccine is stopped