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Key Clinical Message: This case report highlights the importance of recognizing and accurately diagnosing ganglioneuroblastoma, an uncommon variant of neuroblastic tumors in children. Ganglioneuroblastomas have diverse clinical and morphological presentations, and histopathological examination is paramount in guiding treatment decisions, especially in cases with ambiguous symptoms. Early detection is crucial, as the prognosis varies significantly based on the subtype and the presence of metastatic disease. Clinicians should maintain a high index of suspicion and utilize radiological examinations to promptly identify and treat these tumors. Abstract: Children are frequently affected by neuroblastic tumors, which grow from the sympathoadrenal lineage of the neural crest during its development. However, intermixed ganglioneuroblastomas are far less common within the same tumor spectrum, the diagnosis of which could become challenging amidst an unusual presentation. In our case report, we present a 4-year-old boy who had complaints of fever and difficulty in walking, with a supra-renal mass on ultrasound, which was diagnosed as ganglioneuroblastoma-intermixed type on histopathological examination. This report aims to contribute to the understanding of the diverse clinical and morphological spectrum of ganglioneuroblastomas and the importance of multidisciplinary collaboration and histopathological examination to enhance decision-making in such ambiguous scenarios.
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Norovirus infection in children on treatment for acute lymphoblastic leukemia can lead to severe morbidity due to chronic viral shedding, malabsorption, failure to thrive, and interruption of chemotherapy. We had four children with norovirus diarrhoea in eight years period in our pediatric oncology unit. Three children under two years of age had chronic noroviral shedding and persistent diarrhoea, probably due to poor adaptive immune responses. Two of those children didn't respond to nitazoxanide and succumbed to the illness. The third patient who received nitazoxanide and favipiravir, is currently well on chemotherapy.
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The emergence of vaccine-derived polioviruses (VDPVs) in patients with Primary Immunodeficiency (PID) is a threat to the polio-eradication program. In a first of its kind pilot study for successful screening and identification of VDPV excretion among patients with PID in India, enteroviruses were assessed in stool specimens of 154 PID patients across India in a period of two years. A total of 21.42% of patients were tested positive for enteroviruses, 2.59% tested positive for polioviruses (PV), whereas 18.83% of patients were positive for non-polio enteroviruses (NPEV). A male child of 3 years and 6 months of age diagnosed with Hyper IgM syndrome was detected positive for type1 VDPV (iVDPV1) with 1.6% nucleotide divergence from the parent Sabin strain. E21 (19.4%), E14 (9%), E11 (9%), E16 (7.5%), and CVA2 (7.5%) were the five most frequently observed NPEV types in PID patients. Patients with combined immunodeficiency were at a higher risk for enterovirus infection as compared to antibody deficiency. The high susceptibility of PID patients to enterovirus infection emphasizes the need for enhanced surveillance of these patients until the use of OPV is stopped. The expansion of PID surveillance and integration with a national program will facilitate early detection and follow-up of iVDPV excretion to mitigate the risk for iVDPV spread.
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Ewing sarcoma is one of the rare, highly malignant neuroectodermal tumors frequently involving bones. Primary orbital Ewing sarcoma is extremely uncommon. We report a rare case of a 5-year-old boy who presented to us with a painless, slow-growing mass above the medial canthus of the left eye, the clinical appearance of which was masquerading as an internal angular dermoid. The child was subsequently diagnosed to have primary orbital Ewing sarcoma. Primary orbital Ewing sarcoma is a rare tumor with poor prognosis, poses diagnostic challenges, and demands a high index of clinical suspicion.
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Cirrhosis is usually a late-onset and life-threatening disease characterized by fibrotic scarring and inflammation that disrupts liver architecture and function. While it is typically the result of alcoholism or hepatitis viral infection in adults, its etiology in infants is much less understood. In this study, we report 14 children from ten unrelated families presenting with a syndromic form of pediatric liver cirrhosis. By genome/exome sequencing, we found recessive variants in FOCAD segregating with the disease. Zebrafish lacking focad phenocopied the human disease, revealing a signature of altered messenger RNA (mRNA) degradation processes in the liver. Using patient's primary cells and CRISPR-Cas9-mediated inactivation in human hepatic cell lines, we found that FOCAD deficiency compromises the SKI mRNA surveillance pathway by reducing the levels of the RNA helicase SKIC2 and its cofactor SKIC3. FOCAD knockout hepatocytes exhibited lowered albumin expression and signs of persistent injury accompanied by CCL2 overproduction. Our results reveal the importance of FOCAD in maintaining liver homeostasis and disclose a possible therapeutic intervention point via inhibition of the CCL2/CCR2 signaling axis.
Subject(s)
Liver Cirrhosis , Tumor Suppressor Proteins , Adult , Animals , Child , Hepatocytes/metabolism , Humans , Liver/metabolism , Liver Cirrhosis/genetics , Liver Cirrhosis/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Syndrome , Tumor Suppressor Proteins/genetics , Zebrafish/geneticsABSTRACT
OBJECTIVES: To study the incidence, clinical manifestations, and genetic spectrum of primary immunodeficiency diseases (PID)/inborn errors of immunity (IEI) in a tertiary care hospital in Southern India. METHODS: A retrospective analysis of all patients with a clinical suspicion of PID/IEI seen at a tertiary care hospital was performed. All patients had at least one or more warning signs of PID. Serum immunoglobulin levels and other targeted investigations were performed as warranted by the clinical presentation. All families with suspected PID were counseled and offered genetic testing. RESULTS: A total of 225 children were evaluated for PID during the study period of 6 y. Fifty-six of them did not meet the European Society of Immunodeficiencies (ESID) criteria (working definition of clinical diagnosis) and were excluded. An IEI was found in 30/49 (61.2%) patients. The most frequent reason for referral was recurrent/unusual or serious infections (28%), or cytopenia (16%). Group IV diseases of immune dysregulation was the most common category (19%), followed by group III predominant antibody deficiencies in 23/163 (14%), as per the International Union of Immunological Societies (IUIS) classification. CONCLUSIONS: This study highlights the heterogeneity of the present cohort, the underuse of genetic tests, and efforts to provide optimal care for children with possible IEI in this center.
Subject(s)
Immunologic Deficiency Syndromes , Primary Immunodeficiency Diseases , Child , Humans , Immunologic Deficiency Syndromes/diagnosis , Immunologic Deficiency Syndromes/epidemiology , Immunologic Deficiency Syndromes/genetics , India/epidemiology , Primary Immunodeficiency Diseases/genetics , Retrospective Studies , Tertiary Care CentersABSTRACT
Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer. There has been a discovery of 22 FANC genes known to be involved in the FA pathway. This wide number of pathway components makes molecular diagnosis challenging for FA. We present here the most comprehensive molecular diagnosis of FA subjects from India. We observed a high frequency (4.42 ± 1.5 breaks/metaphase) of chromosomal breakages in 181 FA subjects. The major clinical abnormalities observed were skin pigmentation (70.2%), short stature (46.4%), and skeletal abnormalities (43.1%), along with a few minor clinical abnormalities. The combination of Sanger sequencing and Next Generation Sequencing could molecularly characterize 164 (90.6%) FA patients and identified 12 different complementation groups [FANCA (56.10%), FANCG (16.46%), FANCL (12.80%), FANCD2 (4.88%), FANCJ (2.44%), FANCE (1.22%), FANCF (1.22%), FANCI (1.22%), FANCN (1.22%), FANCC (1.22%), FANCD1 (0.61%) and FANCB (0.61%)]. A total of 56 novel variants were identified in our cohort, including a hotspot variant: a deletion of exon 27 in the FANCA gene and a nonsense variant at c.787 C>T in the FANCG gene. Our comprehensive molecular findings can aid in the stratification of molecular investigation in the diagnosis and management of FA patients.
Subject(s)
Fanconi Anemia , DNA Helicases , Fanconi Anemia/diagnosis , Fanconi Anemia/genetics , Fanconi Anemia Complementation Group Proteins/genetics , Fanconi Anemia Complementation Group Proteins/metabolism , Humans , IndiaABSTRACT
Background: Wiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India. Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with PID. Six centers provided requisite data that were compiled and analyzed. Results: In this multi-institutional cohort, clinical details of 108 patients who had a provisional diagnosis of WAS were received. Of these, 95 patients with 'definite WAS' were included Fourteen patients were classified as XLT and 81 patients as WAS. Median age at onset of symptoms of patients was 3 months (IQR 1.6, 6.0 months) and median age at diagnosis was 12 months (IQR 6,48 months). Clinical profile included bleeding episodes (92.6%), infections (84.2%), eczema (78.9%), various autoimmune manifestations (40%), and malignancy (2.1%). DNA analysis revealed 47 variants in 67 cases. Nonsense and missense variants were the most common (28.4% each), followed by small deletions (19.4%), and splice site defects (16.4%). We also report 24 novel variants, most of these being frameshift and nonsense mutations resulting in premature termination of protein synthesis. Prophylactic intravenous immunoglobulin (IVIg) was initiated in 52 patients (54.7%). Hematopoietic stem cell transplantation (HSCT) was carried out in 25 patients (26.3%). Of those transplanted, disease-free survival was seen in 15 patients (60%). Transplant related mortality was 36%. Outcome details were available for 89 patients. Of these, 37% had died till the time of this analysis. Median duration of follow-up was 36 months (range 2 weeks- 12 years; IQR 16.2 months- 70 months). Conclusions: We report the first nationwide cohort of patients with WAS from India. Bleeding episodes and infections are common manifestations. Mortality continues to be high as curative therapy is not accessible to most of our patients.
Subject(s)
Developing Countries , Mutation , Wiskott-Aldrich Syndrome Protein/genetics , Wiskott-Aldrich Syndrome/genetics , Age Factors , Child, Preschool , Disease-Free Survival , Female , Genetic Predisposition to Disease , Hematopoietic Stem Cell Transplantation , Humans , Immunoglobulins, Intravenous/administration & dosage , India , Infant , Male , Phenotype , Risk Assessment , Risk Factors , Time Factors , Wiskott-Aldrich Syndrome/diagnosis , Wiskott-Aldrich Syndrome/immunology , Wiskott-Aldrich Syndrome/therapyABSTRACT
Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.
Subject(s)
Genetic Predisposition to Disease/genetics , Immunity, Innate/genetics , Mutation , Mycobacterium Infections/genetics , Mycobacterium Infections/immunology , Adolescent , Adult , BCG Vaccine/immunology , Child , Child, Preschool , Coinfection/epidemiology , Coinfection/microbiology , Female , Genetic Predisposition to Disease/epidemiology , Humans , India/epidemiology , Infant , Infant, Newborn , Male , Mycobacterium Infections/epidemiology , Mycobacterium Infections/microbiology , Phenotype , Receptors, Interleukin-12/genetics , Receptors, Interleukin-12/immunology , Retrospective Studies , Young AdultABSTRACT
Background: Chronic granulomatous disease (CGD) is an inherited defect in phagocytic respiratory burst that results in severe and life-threatening infections in affected children. Single center studies from India have shown that proportion of autosomal recessive (AR) CGD is more than that reported from the West. Further, affected patients have high mortality rates due to late referrals and difficulties in accessing appropriate treatment. However, there is lack of multicentric collaborative data on CGD from India. Objective: To describe infection patterns, immunological, and molecular features of CGD from multiple centers in India. Methods: A detailed proforma that included clinical and laboratory details was prepared and sent to multiple centers in India that are involved in the care and management of patients with inborn errors of immunity. Twelve centers have provided data which were later pooled together and analyzed. Results: Of the 236 patients analyzed in our study, X-linked and AR-CGD was seen in 77 and 97, respectively. Male female ratio was 172:64. Median age at onset of symptoms and diagnosis was 8 and 24 months, respectively. Common infections documented include pneumonia (71.6%), lymphadenitis (31.6%), skin and subcutaneous abscess (23.7%), blood-stream infection (13.6%), osteomyelitis (8.6%), liver abscess (7.2%), lung abscess (2.9%), meningoencephalitis (2.5%), splenic abscess (1.7%), and brain abscess (0.9%). Forty-four patients (18.6%) had evidence of mycobacterial infection. Results of molecular assay were available for 141 patients (59.7%)-CYBB (44.7%) gene defect was most common, followed by NCF1 (31.9%), NCF2 (14.9%), and CYBA (8.5%). While CYBA variants were documented only in Southern and Western parts of India, a common dinucleotide deletion in NCF2 (c.835_836delAC) was noted only in North Indian population. Of the 174 patients with available outcome data, 67 (38.5%) had expired. Hematopoietic stem cell transplantation was carried out in 23 patients, and 12 are doing well on follow-up. Conclusions: In India, proportion of patients with AR-CGD is higher as compared to Western cohorts, though regional differences in types of AR-CGD exist. Clinical profile and mortality rates are similar in both X-linked and AR-CGD. However, this may be a reflection of the fact that milder forms of AR-CGD are probably being missed.
Subject(s)
Granulomatous Disease, Chronic/immunology , Hematopoietic Stem Cell Transplantation , Skin/pathology , Child, Preschool , Female , Granulomatous Disease, Chronic/genetics , Granulomatous Disease, Chronic/mortality , Humans , India , Infant , Lymphadenitis , Male , Mutation/genetics , NADPH Oxidase 2/genetics , NADPH Oxidases/genetics , Phagocytosis/genetics , Pneumonia , Survival AnalysisABSTRACT
Introduction: Hyper-IgE Syndrome (HIES) is a rare inborn error of immunity (IEI) characterized by a constellation of symptoms related to susceptibility to Staphylococcal skin and pulmonary infections, eczema, raised serum IgE (>2,000 IU/ml), craniofacial anomalies, and recurrent bone fractures. Data on HIES from the Indian subcontinent is scarce and restricted to small case series and case reports. This is the first compilation of national data on HIES. Materials and Methods: A total 103 cases clinically diagnosed and treated as HIES were analyzed from nine centers. Cases with clinical and/or molecular diagnosis of DOCK8 deficiency were not included. Patients were divided into two groups: group I for whom a heterozygous rare variant of STAT3 was identified, and group II, with clinical features similar to those of AD STAT3 deficiency, but without any genetic diagnosis. Results: Genetic diagnosis was available in 27 patients (26.2%) and all harbored rare variants in the STAT3 gene. Majority of these STAT3 HIES patients presented with recurrent skin abscesses (77.7%) or pneumonia (62.9%) or both (59.2%). Other features included eczema (37%), candidiasis (55.5%), facial dysmorphism (55.5%), recurrent fractures (11.1%), and retained primary teeth (7.4%). Mycobacterial infections were seen in a significant 18.5%. Mortality was seen in three subjects (11.1%). A similar trend in the clinical presentation was observed when all the 103 patients were analyzed together. Twenty percent of patients without a rare variant in the STAT3 gene had an NIH score of ≥40, whereas, 51.9% of STAT3 HIES subjects had scores below the cut off of ≥40. TH17 cell numbers were low in 10/11 (90.9%) STAT3 HIES tested. Rare variants observed were 8 in exon 21; 8 in exon 13; 3 in exon 10; 2 in exon 15, and one each in exon 6, 16, 17, 19, 22, and splice site downstream of exon 12. Seven variants were novel and included F174S, N567D, L404Sfs*8, G419 =, M329K, T714I, R518X, and a splice site variant downstream of exon 12. Conclusions: The report includes seven novel STAT3 variants, including a rare linker domain nonsense variant and a CC domain variant. Mycobacterial diseases were more frequent, compared to western literature.
Subject(s)
Job Syndrome/diagnosis , Job Syndrome/genetics , STAT3 Transcription Factor/genetics , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Eczema , Female , Humans , Immunoglobulin E/immunology , India , Infant , Job Syndrome/drug therapy , Job Syndrome/immunology , Male , Multicenter Studies as Topic , Mutation , STAT3 Transcription Factor/deficiency , SkinABSTRACT
Prenatal Diagnosis (PND) forms an important part of primary preventive management for families having a child affected with primary immunodeficiency. Although individually sparse, collectively this group of genetic disorders represents a significant burden of disease. This paper discusses the prenatal services available for affected families at various centers across the country and the challenges and ethical considerations associated with genetic counseling. Mutation detection in the index case and analysis of chorionic villous sampling or amniocentesis remain the preferred procedures for PND and phenotypic analysis of cordocentesis sample is reserved for families with well-characterized index case seeking PND in the latter part of the second trimester of pregnancy. A total of 112 families were provided PND services in the last decade and the presence of an affected fetus was confirmed in 32 families. Post-test genetic counseling enabled the affected families to make an informed decision about the current pregnancy.
Subject(s)
Primary Immunodeficiency Diseases/diagnosis , Amniocentesis/methods , Female , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/genetics , Genetic Testing/methods , Humans , India , Mutation/genetics , Pregnancy , Prenatal Diagnosis/methods , Primary Immunodeficiency Diseases/geneticsABSTRACT
OBJECTIVES: Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in children. With improved supportive care and a better understanding of the disease biology, it is now a curable cancer in the developed world. However, in low-income countries, the cure rate remains relatively poor. We report our experience on the survival of children with ALL treated on the MRD-based risk-stratified UKALL 2003 protocol, from a center in South India. METHODS: All consecutive children diagnosed with ALL between years 2013 and 2019 were included in this retrospective study. All received uniform treatment as per the UKALL 2003 protocol based on NCI risk and post-induction MRD status. All the details including the type of leukemia, NCI risk status, date of diagnosis, treatment start date, the regimen, MRD status, cytogenetics, molecular genetics, and complications were captured. Analysis was done using prism GraphPad version 8.0. RESULTS: A total of 107 children were started on treatment during this period. The majority of them were boys (68/107). Fifty-nine of them were NCI standard risk (55%). B-ALL was the most common type (92%).Total of 56/107(52.3%) children received treatment under the government's insurance scheme for low-income bracket. The post-induction MRD was performed in 95/107 children. It was >0.01% in 22% (21/95) of children. Five (4.7%) children relapsed so far with a mean follow up of 27 months from the diagnosis. There were 17 deaths (15.9%). The EFS at 3 years was 85% (95% CI 75% to 92%). CONCLUSION: It is feasible to deliver chemotherapy as per the UKALL2003 protocol without any modifications in resource-limited setting. The survival rates have significantly improved over the years in our center from 5 years EFS of 60% in 2010 and now to 3 year EFS of 85%. It is important to note that there was no treatment abandonment in our cohort.
Subject(s)
Delivery of Health Care , Health Resources , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Adolescent , Age Factors , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor , Biopsy , Child , Child, Preschool , Clinical Decision-Making , Disease Management , Female , Genetic Testing , Humans , India/epidemiology , Infant , Male , Neoplasm, Residual/diagnosis , Neoplasm, Residual/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prognosis , Socioeconomic Factors , Treatment OutcomeABSTRACT
Background: Severe Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce. Objective: To describe clinical and laboratory features of SCID diagnosed at immunology centers across India. Methods: A detailed case proforma in an Excel format was prepared by one of the authors (PV) and was sent to centers in India that care for patients with primary immunodeficiency diseases. We collated clinical, laboratory, and molecular details of patients with clinical profile suggestive of SCID and their outcomes. Twelve (12) centers provided necessary details which were then compiled and analyzed. Diagnosis of SCID/combined immune deficiency (CID) was based on 2018 European Society for Immunodeficiencies working definition for SCID. Results: We obtained data on 277 children; 254 were categorized as SCID and 23 as CID. Male-female ratio was 196:81. Median (inter-quartile range) age of onset of clinical symptoms and diagnosis was 2.5 months (1, 5) and 5 months (3.5, 8), respectively. Molecular diagnosis was obtained in 162 patients - IL2RG (36), RAG1 (26), ADA (19), RAG2 (17), JAK3 (15), DCLRE1C (13), IL7RA (9), PNP (3), RFXAP (3), CIITA (2), RFXANK (2), NHEJ1 (2), CD3E (2), CD3D (2), RFX5 (2), ZAP70 (2), STK4 (1), CORO1A (1), STIM1 (1), PRKDC (1), AK2 (1), DOCK2 (1), and SP100 (1). Only 23 children (8.3%) received hematopoietic stem cell transplantation (HSCT). Of these, 11 are doing well post-HSCT. Mortality was recorded in 210 children (75.8%). Conclusion: We document an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India. We suspect that these numbers are just the tip of the iceberg. Majority of patients with SCID in India are probably not being recognized and diagnosed at present. Newborn screening for SCID is the need of the hour. Easy access to pediatric HSCT services would ensure that these patients are offered HSCT at an early age.
Subject(s)
Severe Combined Immunodeficiency/epidemiology , Severe Combined Immunodeficiency/genetics , Severe Combined Immunodeficiency/immunology , Female , Humans , India/epidemiology , Infant , MaleABSTRACT
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).
Subject(s)
Severe Combined Immunodeficiency/genetics , Severe Combined Immunodeficiency/immunology , AIDS-Related Opportunistic Infections/diagnosis , Age of Onset , Biomarkers , CD4-CD8 Ratio , Child, Preschool , Combined Modality Therapy , Disease Susceptibility , Female , Gene Expression Profiling , Genetic Variation , Humans , India , Infant , Infant, Newborn , Lymphocyte Count , Male , Severe Combined Immunodeficiency/diagnosis , Severe Combined Immunodeficiency/virology , Symptom AssessmentABSTRACT
Nanjegowda CK, Kamath SP, Kamath P, Shah TD, Kulkarni V, Lashkari HP, Baliga BS. Comparison of diastolic function in children with transfusion dependent beta thalassemia major by tissue and conventional doppler imaging indices and its correlation with serum ferritin levels. Turk J Pediatr 2019; 61: 250-259. Regular blood transfusions for children with beta thalassemia major (ß- TM) results in iron overload cardiomyopathy/cardiac failure. Mortality in these children is most often because of heart failure. We compared Tissue Doppler Imaging (TDI) and conventional pulse wave Doppler (PWD) indices in evaluating diastolic function in chronically transfused ß-TM children and correlated the Doppler indices with mean serum ferritin levels. This was a prospective cross-sectional study conducted at tertiary teaching hospital. ß-TM children aged 3 to 18 years were enrolled as per inclusion criteria. PWD parameters at the mitral inflow (E, A, E/A and DT) and TDI parameters at the medial mitral annulus (E'and E/E') were used for estimation of diastolic dysfunction. Of the 66 children with thalassemia, the mean age was 10.2±3.77yrs and 60.6% were boys. The E/E' ratio estimated diastolic dysfunction (34/66, 51.5%) greater than four times that assessed by E/A ratio indices (8/66, 12.1%) in the subjects. Association of serum ferritin levels with E/E' ratio by chi square test was significant statistically (P=0.027), however was not significant with E/A ratio. By Mann Whitney test, the median serum ferritin levels (ng/ml) were higher [4034.50, (IQR-2084-5340.25) in those with diastolic dysfunction (abnormal E/E'), when compared to those with normal E/E'[2037.50(1510.75- 3572.25)], with their difference being significant (p=0.011), however serum ferritin levels were not significant with E/A ratio and DT. E/E' parameter had a sensitivity and specificity of 76.5% and 53.1% respectively at a mean serum ferritin cutoff level of 2076 ng/mL by ROC analysis. In conclusion, TDI is a more reliable modality for diagnosing early diastolic dysfunction when compared to PWD. Threshold level of serum ferritin greater than 2076 ng/mL is associated with increased incidence of diastolic dysfunction.
Subject(s)
Blood Transfusion , Echocardiography, Doppler/methods , Ferritins/blood , Heart Ventricles/diagnostic imaging , Ventricular Function, Left/physiology , beta-Thalassemia/physiopathology , Adolescent , Biomarkers/blood , Child , Child, Preschool , Cross-Sectional Studies , Diastole , Female , Heart Ventricles/physiopathology , Humans , Male , Prognosis , Prospective Studies , ROC Curve , beta-Thalassemia/blood , beta-Thalassemia/diagnosisABSTRACT
Sertoli-Leydig cell tumors are rare ovarian neoplasms. We report two unusual cases with bilateral SLCTs suggesting evidence of genetic predisposition and at high risk of recurrence. To reduce this risk, we exploited the use of GnRH analog to lower gondadotropin and potentially directly inhibit the tumors through expressed GnRH receptors. We used it as maintenance antitumor therapy for 2 years after completion of chemotherapy, to cover the period of risk for recurrence. Both patients remain in complete remission at >2 years after completing leuprorelin therapy. Of note, both patients carry DICER1 mutations, frequently found in pleuropulmonary blastoma syndrome.
Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Leuprolide/therapeutic use , Ovarian Neoplasms/drug therapy , Sertoli-Leydig Cell Tumor/drug therapy , Child , Female , Gonadotropin-Releasing Hormone/analogs & derivatives , Humans , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/pathology , Sertoli-Leydig Cell Tumor/pathologyABSTRACT
Neuroblastoma in a known case of congenital adrenal hyperplasia has rarely been reported. The management of such a patient in the background of hormonal imbalance can be very challenging. In this report, we share our experience in managing such a child and discuss the clinical dilemma.