Spectrum of Primary Immunodeficiency Disorders in Hospitalized Children: Multicentric Data From Kolkata.

OBJECTIVE: To evaluate the incidence and types of primary immunodeficiency diseases (PIDs) in hospitalized children with infection. METHODS: This prospective study was conducted in five tertiary-care facilities in Kolkata over two consecutive years between November 1, 2018 and October 31, 2020. We included all children aged upto 12years who were hospitalized and screened them for PID. Children were screened for suspected IPD using Jeffrey Modell Foundation (JMF) Criteria; any child who satisfied at least 2 out of 10 warning signs was further evaluated for PIDs. RESULTS: Out of 33,204 hospital admissions, 50 children satisfied JMF criteria. Out of 50 children screened during the study period, 27 were finally diagnosed with an underlying PID, with a prevalence of 1 in 1000 hospitalized children. Majority (37.03%) of them had antibody deficiency followed by phagocytic defect (33.3%). Chronic granulomatous disease was the commonest PID followed by common variable immunodeficiency. Around 62.97% children presented with respiratory infections and overall Acinetobacter baumannii was the commonest isolated organism. CONCLUSION: Our study presents the first cohort of PID from eastern India. A methodical step-wise clinical and diagnostic approach can facilitate early diagnosis and timely therapeutic interventions.

Autoimmune diseases post-COVID 19 infection in children in intensive care unit: A case series.

SARS-CoV2 primarily affects the respiratory system but a hyperinflammatory response leading to multisystem inflammatory syndrome - children (MIS-C), immune dysfunction and various autoimmune manifestations has also been noted. Autoimmunity depends on various factors, including genetic predisposition, environmental factors, immune dysregulation and infections acting as triggers like Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, hepatitis B. Molecular mimicry, bystander T-cell activation and persistence of viral infection are the main mechanisms behind these manifestations. We present here 3 cases of newly diagnosed connective tissue disease with high titers of COVID19 immunoglobulin G antibody in children. A 9-year-old girl with fever, oliguria and malar rash (prior history of sore throat) and a 10-year-old girl with fever for 2 weeks and choreoathetoid movements were diagnosed as systemic lupus erythematosus (SLE) nephritis (stage 4) and neuropsychiatric SLE, respectively as per European League Against Rheumatism / American College of Rheumatology 2019 criteria. An 8-year-old girl with fever, joint pain and respiratory distress (a recent contact with a positive COVID19 patient) presented with altered sensorium, Raynaud's phenomenon noted, and eventually diagnosed as mixed connective tissue disease as per Kusukawa criteria. The immune-mediated manifestations post-COVID infection are a de-novo phenomenon which necessitates further workup as not many studies exist in the pediatric population.

Survey of musculoskeletal abnormalities in school-going children of hilly and foothill regions of Eastern Himalayas using the pediatric Gait, Arms, Legs, Spine screening method.

OBJECTIVE: To study the prevalence and pattern of musculosketetal abnormalities in school-going children living in the hilly and foothill regions of the Eastern Himalayas using the pediatric Gait, Arms, Legs, Spine (pGALS) screening tool. METHODS: Total of 3608 children, aged 3-12 years were enrolled from 16 schools (5 in the hills) in the eastern Himalayan region. After the three screening questions, the pGALS maneuvers were administered. Subjects were shown a video on pGALS before the actual testing. Those detected to have abnormality were probed in greater detail and referred for treatment as necessary. RESULTS: The pGALS examination was completed in 3463 children with a median time of 3 min (range 1.9-5.4 min). The abnormality pattern was in the order: growing pains (38.86%), hypermobility (25.54%), mechanical pains (24.46%) and others (11.14%). Among mechanical pain, back and neck problems occurred with a similar overall frequency of 7.61%. Similar order was observed considering only children from the pains. However, in hill children, the proportion of mechanical problems (32.28%) exceeded proportion of hypermobility (23.62%). Asymptomatic hypermobility was more common than symptomatic hypermobility. Maximum prevalence of hypermobility was in 6-9 year age group. Of the 94 children with hypermobility, 55.32% had some kind of joint pain. CONCLUSIONS: Pediatric Gait, Arms, Legs, Spine is an acceptable screening tool for musculoskeletal abnormalities in apparently healthy children. Growing pain is the commonest musculoskeletal complaint while hypermobility is the commonest physical abnormality in school-going children in the Eastern Himalayas. Asymptomatic hypermobility is more common than symptomatic hypermobility.

Penile Length and Testicular Volume in Newborns.

OBJECTIVES: To measure Penile length (PL) and Testicular volume (TV) in newborn boys for assessing genital abnormalities. METHODS: In a tertiary care setting, measurements of PL and TV were recorded from 480 babies born on alternate days except the weekend, at 24 to 72 h of life by one investigator with the same set of instruments. The penis was stretched to the point of increased resistance and the distance from the tip of the glans penis to the pubic ramus was measured as the stretched PL. Testicular volume was measured by a Prader orchidometer. Improvised beads made of plasticine were used for recording volumes <1 ml. RESULTS: In the study cohort, 365 (76.04 %) were term babies. The mean PL was 34 ± 4.7 mm for the whole cohort while the corresponding value for mean TV was 0.6 ± 0.2 ml. The gestation age-wise percentile charts of PL and TV have been generated. There was modest positive correlation between PL and TV. Positive correlation was also observed between PL and TV and birth weight, body length, and head, chest and arm circumference. Both PL and TV showed statistically significant increase with gestational age. By the index data, the cut-off for suspecting abnormal penile length should be <24.5 or >45.5 mm for term babies. CONCLUSIONS: The normative values generated can serve as reference standard in the diagnosis of penile length abnormalities in Indian babies and in clarifying issues of ambiguous genitalia and maldevelopment of male external genitalia.

Acute hemorrhagic edema of infancy.

The authors report an 11-mo-old child presenting with acute onset appearance of large, erythematous, palpable purpuric lesions involving face, extremities and trunk. Skin biopsy from the margin of the lesions showed leukocytoclastic vasculitis suggesting a diagnosis of acute hemorrhagic edema of infancy. This rare type of cutaneous vasculitis, despite its grave presentation is a benign condition with self-limiting course.

Patient health questionnaire-9 as an effective tool for screening of depression among Indian adolescents.

PURPOSE: Detection of depression among adolescents in the primary care setting is of paramount importance, especially in resource-constrained countries such as India. This article discusses the diagnostic accuracy, reliability, and validity of the Patient Health Questionnaire-9 (PHQ-9) when pediatricians use it among Indian adolescents. METHODS: Pediatricians administered the PHQ-9 to 233 adolescent students aged 14-18 years, along with the Beck Depression Inventory. Our psychologist clinically diagnosed depression based on an International Classification of Diseases, 10th Revision, interview of participants. One month later, the PHQ-9 was readministered among students. We conducted appropriate analyses for validity and diagnostic accuracy. RESULTS: A total of 31 students (13.3%) had a form of depression on psychiatric interview. A PHQ-9 score of ≥5 was ideal for screening (sensitivity, 87.1%; specificity, 79.7%). In addition to good content validity, PHQ-9 had good 1-month test-retest reliability (r = .875) and internal consistency (Cronbach's α = .835). There was high convergent validity with the Beck Depression Inventory (r = .76; p = .001). The concordance rate between the PHQ-9 threshold score of ≥10 and the International Classification of Diseases, 10th Revision based diagnosis was good (Cohen's κ = .62). The area under the receiver operating characteristic curve for PHQ-9 was .939. CONCLUSIONS: The PHQ-9 is a psychometrically sound screening tool for use by pediatricians in a primary care setting in India. Because it is a short, simple, easy to administer questionnaire, the PHQ-9 has tremendous potential in helping to tackle the growing problem of depression among adolescents in developing countries.

Bilateral giant-sized symmetrical pulmonary hydatid cysts in an 8-year-old girl.

An 8-year-old girl presented with a low-grade fever and cough for 4 weeks and minimal physical findings. Chest radiograph demonstrated two giant hydatid cysts occupying two-thirds of each lung and another two cysts in the liver were detected by ultrasonography. The cysts were resected from both lungs and the liver under albendazole cover. She made a complete recovery.

Probing the role of the fully conserved Cys126 in triosephosphate isomerase by site-specific mutagenesis--distal effects on dimer stability.

Cys126 is a completely conserved residue in triosephosphate isomerase that is proximal to the active site but has been ascribed no specific role in catalysis. A previous study of the C126S and C126A mutants of yeast TIM reported substantial catalytic activity for the mutant enzymes, leading to the suggestion that this residue is implicated in folding and stability [Gonzalez-Mondragon E et al. (2004) Biochemistry 43, 3255-3263]. We re-examined the role of Cys126 with the Plasmodium falciparum enzyme as a model. Five mutants, C126S, C126A, C126V, C126M, and C126T, were characterized. Crystal structures of the 3-phosphoglycolate-bound C126S mutant and the unliganded forms of the C126S and C126A mutants were determined at a resolution of 1.7-2.1 Å. Kinetic studies revealed an approximately five-fold drop in k(cat) for the C126S and C126A mutants, whereas an approximately 10-fold drop was observed for the other three mutants. At ambient temperature, the wild-type enzyme and all five mutants showed no concentration dependence of activity. At higher temperatures (> 40 °C), the mutants showed a significant concentration dependence, with a dramatic loss in activity below 15 µM. The mutants also had diminished thermal stability at low concentration, as monitored by far-UV CD. These results suggest that Cys126 contributes to the stability of the dimer interface through a network of interactions involving His95, Glu97, and Arg98, which form direct contacts across the dimer interface.

Dorfman-Chanarin syndrome: a rare neutral lipid storage disease.

Dorfman-Chanarin syndrome is a rare neutral lipid storage disorder characterized by ichthyosis, lipid vacuolations in peripheral leucocytes, and multisystem involvement. It is an autosomal recessive disorder caused by mutations in the CGI-58 gene. A total of 42 cases have been reported worldwide till February 2009 out of which 4 have been previously reported from India. We report a case of a 20-month-old male with congenital ichthyosis, organomegaly, and bilateral cryptorchidism. Examination of the peripheral smear revealed lipid vacuoles in the leucocytes consistent with Jordan's anomaly, which was confirmed by transmission electron microscopy. Liver biopsy revealed micronodular cirrhosis with macrovesicular steatosis while skin biopsy showed ichthyosis vulgaris. Dorfman-Chanarin syndrome was diagnosed on the basis of clinical and laboratory criteria with certain unreported manifestations. Dietary modifications were instituted and followed up after 1 year with promising results. This emphasizes the importance of neonatal screening for lipid vacuolations in peripheral blood in all cases of congenital ichthyosis.