Background: Neurodevelopmental disorders (NDD) are a major global public health problem, particularly affecting children from the lower- and middle-income countries (LMICs). In India, nearly 2.3 million children below 6 years of age have some developmental disability, of whom many live in rural and semi-urban areas with minimum access to early intervention services. We attempted to reach out to such a population at their doorstep with affordable care and management through home-based early intervention (HBEI) programs provided by local field level workers (hitherto referred as community therapy providers [CTP]). A group of local youth, with a short training on NDD and EI methods, have been providing regular, weekly therapy sessions to the afflicted children at the latter's residence, under constant virtual guidance and monitoring by specialists, with the help of a mobile application. The children were initially screened and assessed by our specialist team, who assigned the therapy program and demonstrated the techniques to the CTPs. Clinical Description: We are sharing a series of 8 cases, ranging from cerebral palsy to Global Developmental Delay and speech delay, who have received HBEI for 3–5 months, to demonstrate the impact of the program. Management and Outcome: The children have shown improvement in all domains with the intensive and regular services. Moreover, empathy, concern, and inclusion of parents in therapy sessions rejuvenated the families. Conclusion: Provision of HBEI through field workers may be a cost-effective solution to the formidable problem of childhood disability among the under-privileged rural community. The electronic tracking system has proved very useful in remote monitoring.

Background: India has the dual challenge of a high prevalence of developmental delay and disabilities in early childhood and a paradoxical underutilization of available intervention services due to limited accessibility and acceptability by their families. Early Childhood Development (ECD) services delivered by community health workers (CHWs) ensure its last-mile delivery to every household. IIts acceptability is improved by including evidence-based, culturally, and contextually sensitive approaches as is done in the International Guide for Monitoring Child Development (IGMCD). The IGMCD is a tool that monitors and supports the development of children under 3 years of age and also enables provision of early intervention services when required. The IGMCD, recognizes caregiver strengths and priorities and helps to build a rapport between caregivers and providers. Clinical Description: We describe six children and their families from Velugam, Dadra-Nagar Haveli district, who received ECD services from CHWs who used the IGMCD package. These cases highlight how the CHWs used the IGMCD package to identify developmental delays, health and psychosocial risk factors to development and provide strategies to caregivers to support their children's development. Management: The CHW used individualized strategies to promote responsive caregiving and enhance opportunities for early learning. In addition, the IGMCD package reinforces health, nutrition, and ECD-directed messages that are provided at the Anganwadi centers. Conclusion: Children and families in underserved communities can receive comprehensive ECD services through CHWs who are trained to deliver the IGMCD.

Background: Kawasaki disease (KD) is a medium-vessel vasculitis that commonly affects young children. Many atypical presentations that differ from the classical phenotype have been described. Clinical Description: A 3-year-old boy presented with acute onset refusal to walk due to severe pain in both lower limbs for 8 days. This was accompanied by fever for 7 days. Significant findings included diffuse tenderness of bilateral thighs and leg muscles, probable normal joints, and absence of rashes, edema, significant lymphadenopathy, organomegaly, or paralysis. He had a hemoglobin of 10.6 g/dL, neutrophilic leukocytosis, and normal platelet count (384 × 10⁹/L). He was started on intravenous cloxacillin, assuming polymyositis or acute osteomyelitis. Radiographs, ultrasonography, and bone scan of the lower limbs revealed normal bones and joints. However, magnetic resonance imaging detected patchy hyperintensities in multiple muscles, though muscle-specific enzyme levels were normal. The fever and pain persisted and investigations for other differentials (including classical KD) were inconclusive. At the end of 2nd week of illness, atypical KD was suspected, when he developed periungual skin peeling with increasing erythrocyte sedimentation rate and platelet counts. Management: The diagnosis was confirmed by echocardiogram proven left main coronary artery dilatation. He was started on intravenous immunoglobulin. Since fever persisted, a second dose was administered, following which defervescence occurred and his symptoms subsided. Conclusions: Atypical KD should be considered in a fever of unknown origin when diagnostic criteria of classical KD are not satisfied. Polymyositis and panniculitis are uncommon atypical manifestations.

Background: Behavioral phenotypes are observable patterns of behavior present in certain genetic syndromes that have distinctive social, linguistic, cognitive, and motor profiles. These may play an important role as pointers toward certain genetic disorders. The recognition of aberrant behavior is important for therapeutic targeting by behavioral modification strategies and medication. The repertoire of behavioral constellations is exhaustive, but common manifestations include aggression, self-injury, autistic features, and a happy demeanor comprising excessive smiling and outbursts of laughter without any preceding triggers. Clinical Description: We describe the approach that was used to establish diagnosis in a boy with a happy disposition, cognitive impairment, and seizures, the firstborn of a couple desiring genetic counseling for their second 7-week pregnancy. After deep phenotyping (identifying overt and concealed dysmorphism, assessment of vision, hearing, behavior, and cognition), a syndrome search was performed by a geneticist using suitable handles. The clinical phenotype of the proband was then matched with the generated list of disorders. The most likely diagnosis Angelman syndrome (AS) was excluded by negative specific genetic testing. Chromosomal microarray identified 2q23.1 microdeletion that is associated with pseudo-AS. Prenatal diagnosis at 16 weeks revealed an unaffected fetus. Management: There is no cure for this syndrome. Affected children benefit from symptomatic intervention provided by a multidisciplinary team including clinical geneticists, pediatricians, pediatric neurologists, developmental pediatricians, and various professional therapists. Conclusions: Behavioral phenotypes aid in establishing diagnosis in certain genetic disorders. A happy disposition coupled with intellectual disability should prompt the clinician to involve a geneticist in management, even if overt dysmorphism is not apparent.

Background: Immunoglobulin A vasculitis (IgAV), previously known as Henoch–Schonlein purpura (HSP), is the most common vasculitis in children. Previous studies have identified various triggers of IgAV, with infections being the most common. We present herein a 9-year-old girl who developed IgAV with nephritis following a wasp sting. Clinical Description: A 9-year-old girl presented to us with a history of wasp sting 7 days ago, followed by the appearance of reddish, raised rashes over the back of her lower limbs, which later spread all over the body. She also developed edema over the face, abdomen, and lower limbs along with pain abdomen. On examination, she was afebrile, was normotensive, and had periorbital edema and bilateral pedal edema with multiple discrete palpable, nonblanching purpura predominantly over the extensor surfaces of the lower and upper extremities and the trunk. Abdominal examination revealed no tenderness. Complete blood counts, blood urea, serum creatinine, and liver function tests were normal. Urinalysis showed microscopic hematuria and nephrotic range proteinuria. Skin biopsy of the lesions showed evidence of IgA vasculitis. Renal biopsy was suggestive of HSP nephritis class 3. Management and Outcome: She was managed with oral corticosteroids, mycophenolate mofetil, and enalapril and had remission of proteinuria. The renal function tests and blood pressure continue to be normal. Conclusion: Few case reports exist of IgAV precipitated by insect bites; however, we could not find any previous reports of IgAV with nephritis following a wasp sting in children. This report adds to existing knowledge regarding precipitating factors for IgAV in children.

Background: Aluminum phosphides (ALPs) are still being used in developing countries as a pesticide despite the fact that ingestion and/or inhalation can cause significant morbidity and mortality. The generation of phosphine when ALP comes in contact with water leads to the blockade of electron transfer, which inhibits oxidative phosphorylation and in turn, cellular respiration in multiple organ systems. Clinical Description: A 3-year-old Turkish girl and her family were inadvertently exposed to overnight inhalation intoxication after a tablet of ALP was dissolved in water and used as a pesticide for Isot pepper, a local spice used in their household. The child presented with rapidly progressive respiratory distress and coma. The other members displayed mild respiratory symptoms. Management: At the time of admission, she was in altered sensorium, tachycardic, tachypneic, hypoxic, and in shock. She was immediately intubated and intermittent positive pressure ventilation started. Shock was managed as per the standard protocol. The child emanated garlic odor breath, had sluggishly reactive bilateral mitotic pupils. She had cardiorespiratory arrest within 30 min of intubation and could be revived. Despite supportive treatment, multiorgan dysfunction syndrome developed cardiac, pulmonary, renal, hepatic, coagulopathy, hyperglycemia, and metabolic acidosis. She succumbed to another cardiorespiratory arrest before plasmapheresis and continuous renal replacement therapy could be started in an attempt to eliminate the toxins. Consent for autopsy was not given. Conclusions: ALPs poisoning still occurs in developing countries and is a leading cause of mortality. The most common cause of death within the first 24 h is cardiovascular collapse.

Background: Chronic intestinal pseudo-obstruction (CIPO) is an umbrella term for a range of different conditions characterized by repetitive episodes or continuous symptoms and signs of bowel obstruction, including radiographic evidence of dilated intestines and air-fluid levels, due to impaired propulsion in the absence of an anatomical occluding lesion. It is a diagnostic challenge and can mimic Hirschsprung's disease. Clinical Description: A 10-month-old boy presented with a history of recurrent episodes of constipation since the age of 6.5 months. The first two had resolved with symptomatic treatment. The third had been associated with bilious vomiting and required exploratory laparotomy. He was referred to us when there was no symptomatic improvement. The child underwent extensive workup that included a review of earlier investigations (contrast-enhanced computerized tomography abdomen, barium enema, and sigmoid biopsy) as well as upper gastrointestinal endoscopy, workup for secondary CIPO, esophageal and antroduodenal manometry, genetic studies, for primary CIPO. A laparotomy with concurrent adhesionolysis, appendectomy, gastrostomy, and ileostomy was undertaken, which included full-thickness biopsies at multiple sites. This revealed both degenerative leiomyopathy and eosinophilic myenteric ganglionitis (EMG). Known associations of CIPO, an underactive bladder, and sinus arrhythmias were also detected. Management: The infant was provided with supportive therapy. A trial of steroids was given for the EMG. The child had multiple bad prognostic factors and also protracted multiple nosocomial infections. He succumbed to his illness and complications after 40 days of hospitalization. Conclusion: The combination of EMG and degenerative leiomyopathy has not been reported in CIPO before.

Background: Undiagnosed Type 1 diabetes mellitus (T1DM) often presents as diabetic ketoacidosis (DKA). We report a child with newly diagnosed T1DM who developed anasarca and persistent diarrhea following resolution of DKA and was referred to us for the same. Clinical Description: We reviewed the clinical history, examination, and investigations that had been undertaken. Our clinical evaluation was in concurrence with the referring hospital-anasarca with probable partially treated spontaneous bacterial peritonitis (SBP). However, the cause of the subacute anasarca and persistent diarrhea was unclear. The child was empirically started on broad-spectrum antibiotics for the SBP, a high-protein diet to build up the protein, and continued the same subcutaneous insulin, on which he was euglycemic. After ruling out usual causes, i.e., renal, hepatic, and cardiac, we reviewed the possibility of celiac disease, tuberculosis, insulin edema, and hypothyroidism. Management: When he did not improve despite a good appetite, adherence to management, and all tests were inconclusive, we reviewed the etiopathogenesis. Untreated T1DM had led to chronic negative catabolism that had precipitated severe hypoproteinemia. A vicious cycle had set in which hypoalbuminemia was leading to bowel wall edema, resulting in protein malabsorption, perpetuation of diarrhea, and further hypoproteinemia. Our assumption proved to be correct when a single dose of parenteral albumin broke the cycle, and the child improved drastically with the resolution of diarrhea within 24 h and the edema in a few days. Conclusions: This case highlights the implications of severe catabolism in a patient with untreated diabetes and how this may be a self-perpetuating condition.

Background: Clinical, pathologic, and genetic heterogeneity is a challenge in identifying and classifying congenital dyserythropoietic anemia (CDA). CDA type IV, the rarest CDA with only 11 reported cases, results from KLF1 gene mutation. Clinical Description: A male preterm neonate presented with jaundice, anemia, pulmonary hypertension and hepatosplenomegaly in the immediate postnatal period, requiring multiple red blood cell transfusions. Management and Outcome: The workup for non-immune haemolytic anemia including red blood cell structural and enzymatic studies and were normal, with peripheral blood smear showing multiple polychromatic cells and numerous nucleated red blood cells including binucleate ones and fetal haemoglobin of 91.2%. Genetic testing revealed KLF1 E325K mutation suggestive of CDA type IV, though parental testing was normal, suggesting de novo mutation. The infant has been receiving packed RBC transfusion every three to four weeks initially and then every two months. The baby is now of twelve months of age, and receives oral vitamin B12 and folic acid supplementation for ineffective erythropoiesis. Though his weight is in the 3rd centile for age and height, he has been developmentally normal. Conclusions: Our report, the first description of a CDA type IV diagnosis in the neonatal period, adds to the limited knowledge of this disorder, which we also comprehensively review. The report highlights the phenotype of the disorder and the importance of neonatal genetic testing in a case of transfusion dependent anemia, having ruled out other causes.

Background: Myelin oligodendrocyte glycoprotein encephalomyelitis (MOG-EM) includes patients with (i) monophasic or relapsing acute optic neuritis, myelitis, brainstem encephalitis, or encephalitis; (ii) magnetic resonance imaging (MRI) or electrophysiological evidence of central nervous system (CNS) demyelination; and (iii) MOG-immunoglobulin G (IgG) seropositivity. Clinical Description: A 4-year-old girl presented with fever and excruciating headache for 10 days. Her vitals were stable and systemic examination was normal. Cerebrospinal fluid (CSF) analysis revealed 10 lymphocytes and normal biochemistry. After 5 days, she developed a fever and a seizure. Repeat CSF showed increased cells (60% lymphocytes), normal protein, and sugar. MRI brain was normal. She was managed symptomatically. CSF meningoencephalitis panel was negative. The child improved and was discharged. After 2 weeks, the headache recurred with associated blurring of vision. Bilateral papillitis, MRI brain abnormalities suggestive of acute disseminated encephalomyelitis (EM), and bilateral prolonged latency on visual evoked potential (VEP) were found. Anti-MOG antibodies were positive. The final diagnosis was MOG-EM. Management: The child was started on methylprednisolone therapy as per standard protocol. The vision improved and headache disappeared. She is on regular follow-up and is asymptomatic. Conclusion: MOG-IgG testing should be done in patients with (i) monophasic or relapsing acute optic neuritis, myelitis, brainstem encephalitis, or encephalitis; (ii) radiological or VEP findings compatible with CNS demyelination; and (iii) at least 1 of 25 delineated findings on MRI, fundoscopy, CSF, histopathology, clinical phenotype, or treatment response.

Background: DiGeorge Syndrome (DGS) is caused by the 22q11 deletion. There is wide variation in the phenotypic presentation due to incomplete penetrance. Since dysmorphism is subtle in neonates, a high index of suspicion should be kept. Clinical Description: A 2.8 kg term baby girl born of a cesarean section developed stridor and respiratory distress and was referred to our hospital at 14 days for the persistence of symptoms. The manifestations were severe, requiring respiratory support, and not explainable by clinical findings, radiological atelectasis, and normal echocardiography. The baby had hypocalcemia (that had been noted and treated earlier), hypoparathyroidism and Vitamin D deficiency, for which standard therapy was started. Airway endoscopy revealed hypertrophied arytenoids which have not been reported in DGS before. Management: The presence of abnormal laryngeal with hypocalcemia prompted us to consider DGS. The likelihood became stronger when a chest ultrasonogram detected athymia. The identification of 22q microdeletion by fluorescence in situ hybridization confirmed the diagnosis. It was decided to perform supraglottoplasty to avoid the postoperative complications associated with direct vocal cord repair. The postoperative period was uneventful. The immunological profile was normal, besides a low count of normal CD4+ naïve cells. The final diagnosis was partial DGS. Conclusion: Genetic testing for 22q11 deletion should be done in the presence of laryngeal pathology and any of the following: congenital cardiopathy, velopharyngeal insufficiency, thymic hypoplasia, and neonatal hypocalcemia.

Background: Factor XIII deficiency is a rare autosomal recessive coagulation disorder with varied presentations including prolonged bleeding from the umbilical cord stump, defective wound healing, recurrent miscarriages, or life-threatening intracranial hemorrhage. Clinical Description: A male baby was born at term gestation to a fourth gravida mother with a history of two abortions in the past. He was born out of a third-degree consanguineous marriage, with smooth perinatal transition, but developed multiple episodes of seizures associated with poor feeding and lethargy after 24 h of life. Management: On evaluation, septic screen, metabolic screen (serum electrolytes, calcium, and blood sugar), and coagulation assays were normal. Ultrasonogram revealed a hyperechoic lesion restricted to the left cerebral hemisphere, suggestive of an intraparenchymal hemorrhage. Magnetic resonance imaging brain showed left intraparenchymal hemorrhage with significant mass effect and midline shift. In view of intracranial bleed with normal coagulation assay and other causes being ruled out, factor XIII clot solubility assay was sent and found to have undetectable levels. Factor XIII levels of the mother were also found low (5.5%) though the levels in the father were normal. The baby was managed conservatively with supportive measures in the form of anticonvulsant and anti-edema measures. He recovered successfully and is under close follow-up. Conclusion: A high index of suspicion of factor XIII deficiency should be kept in any neonate presenting with intraparenchymal hemorrhage and recurrent abortions in the mother. This case is being reported to highlight factor XIII deficiency in recurrent pregnancy loss and neonatal intracranial bleeding. Prenatal screening for factor XIII deficiency in these circumstances will help in effective management of future pregnancies.

Background: Neonatal severe primary hyperparathyroidism (NSPHPT) is disorder characterized by severe hypercalcemia and severe hyperparathyroidism resulting from a loss of function of the calcium-sensing receptor (CaSR), encoded by a gene located on the long arm of chromosome 3 (3q-13.3-21). It can be fatal if timely management is not initiated. Clinical Description: A 10-day-old exclusively breastfed girl presented with poor feeding, constipation, and lethargy for 2–3 days before admission. She was born of third-degree consanguinity to a primiparous woman with normal gestation. Born at term, with a birth weight of 3.1 kg, she was discharged uneventfully on day 3 of life. At admission, she was hemodynamically stable and normothermic but exhibited tachypnea, dehydrated with 15% weight loss as compared to birth weight, lethargy, and hypotonia. Salient investigations showed euglycemia, no dyselectrolytemia, and negative sepsis screen, but severe hypercalcemia and hyperparathyroidism. A final diagnosis of NSPHPT was made. Clinical exome sequencing showed homozygous CaSR gene frameshift mutation on chromosome 3. Management: Hypercalcemia was managed initially by standard protocol, including furosemide, hyperhydration, bisphosphonates, and cinacalcet. Subsequently, parathyroidectomy was performed at 2 months of age. Postoperatively, the infant is 5 months old and thriving well. Conclusion: NSPHPT should be considered in the presence of features of clinical sepsis, failure to timely regain birth weight, and a profile suggesting atypical calcium homeostasis.