Background: Cohen syndrome (CS) is caused by an autosomal recessive (AR) mutation of the vacuolar protein sorting 13 homolog B (VPS13B) gene on chromosome 8q22.2. It is characterized by hypotonia, obesity, prominent incisors, and mental retardation. It is diagnosed by the satisfaction of various systems of clinical diagnostic criteria. Molecular confirmation is by clinical exome sequencing. Clinical Description: We reported three siblings from a Kashmiri family with a positive history of consanguinity. The index case, a 26-month-old boy, was diagnosed with neutropenia during the workup for recurrent respiratory infections. He was also noted to have developmental delay, short stature, obesity, microcephaly, and facial dysmorphism. Retinitis pigmentosa was found. The diagnosis of CS was established on the detection of a pathogenic novel homozygous frameshift variant in the VPS13B gene. Evaluation of the family identified two other siblings, an 11-year-old boy and a 9-year-old girl, who satisfied the clinical criteria. Management and Outcome: The parents underwent genetic counseling. The affected children are under follow-up by a multidisciplinary team with regular monitoring of various parameters as per standard recommendations. Conclusion: Pediatricians should consider the application of diagnostic criteria of CS in a child with neutropenia, short stature, developmental delay, and microcephaly, if there is a setting of consanguinity. The diagnosis should be confirmed by genetic testing.

Background: Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disorder of children and young adults. In the setting of the COVID-19 pandemic, we have observed increasing admissions of SSPE and a change in the clinical profile, mainly younger age of presentation, i.e., children under the age of 5 years. Clinical Description: We presented the clinical and investigational characteristics of 20 children who were diagnosed as SSPE during the period March 2020–March 2021 in our hospital, based on the Dyken criteria. The mean age was observed to be 3 years 9 months and male-to-female ratio of 1:1. Most children presented with developmental regression and myoclonic jerks. The clinical details and investigations were presented and a few atypical cases were discussed. Management: All the patients were treated symptomatically: anticonvulsant drugs, nutritional rehabilitation and supported feeding, occupational therapy, and palliative therapy. A trial of isoprinosine was started in all the patients, but was discontinued by most due to the expense. There were no mortalities. Conclusion: The change in profile of SSPE to an earlier onset in the setting of the pandemic should make the clinician keep a high index of suspicion of this disorder in children under the age of five years who present with unexplained developmental regression or acute encephalopathy, before the onset of typical myoclonus.

Background: Guillain–Barre Syndrome (GBS) is an autoimmune polyneuropathy involving mainly motor but also sensory and autonomic nerves. It is considered postinfectious and is been linked with many infectious organisms such as human immunodeficiency virus, Zika virus, and others. Since the onset of the pandemic, a few cases of GBS with a temporal association with SARS-CoV-2 infection has been reported in adults and children. The manifestations are similar to the classic clinical phenotype of progressive, ascending, symmetrical flaccid paralysis of the limbs with areflexia/hyporeflexia, and with or without cranial nerve involvement. This series describe three children with post-COVID GBS. Case Description: Three unrelated boys, 14 years, 11 years, and 7 years in age presented with varying combinations of pain, paraesthesias, and ascending weakness involving their limbs for a few days. We suspected GBS based on the clinical phenotype of rapidly progressive symmetrical weakness. The Modified National Institute of Neurological Disorders and Stroke Criteria for establishing the clinical diagnosis of GBS were satisfied. The typical albuminocytological dissociation in cerebrospinal fluid was observed in all. Management: The GBS was presumed to be postinfectious secondary to the COVID-19 virus in each one, based on elevated COVID-19 immunoglobulin G (IgG) and IgM antibody titers, exclusion of other common infectious organisms, and normal magnetic resonance imaging. All these patients were started on intravenous immunoglobulin and methylprednisolone. Two children recovered without any neurological deficits. The third child expired due to respiratory involvement. Conclusion: COVID-19 infection may result in GBS, the clinical profile of which is similar to that seen after other infectious organisms.

Background: Multisystem inflammatory syndrome in neonates (MIS-N) is hypothesized to be caused either following transplacental transfer of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies or antibodies developed in the neonate after infection with SARS-CoV-2. The common clinical manifestations include fever, respiratory distress, shock, and encephalopathy. Gastrointestinal manifestations include vomiting, diarrhea, bloody stools, and gastric residues. Necrotizing enterocolitis (NEC) has not been described before in MIS-N. Clinical Description: We report a term neonate presenting on day 10 of life with 2 days history of fever, abdominal distension, vomiting, reduced feeding, and not passing stool. He had tachycardia, tachypnea, a distended tense and tender abdomen with absent bowel sounds, and excessive irritability. Salient investigation results were anemia, neutrophilic leukocytosis, hyponatremia, metabolic acidosis, and elevated inflammatory markers. Dilated bowel loops on abdominal radiograph and thickening of bowel wall on abdominal ultrasonography were consistent with NEC. In view of the unusual presentation of NEC, the elevated biomarkers and setting of the pandemic, MIS-N was suspected, investigated, and the diagnostic criteria were found to be satisfied. Management: The baby received supportive care. Methylprednisolone, intravenous immunoglobulin, aspirin, and enoxaparin were started resulting in defervescence and decline in inflammatory markers. However, he developed fixed bowel loops and underwent an exploratory laparotomy. This revealed stricture and extensive necrosis of the terminal ileum with adhesive obstruction. The affected segment was excised, and loop ileo-colostomy was done. He gradually improved and was discharged on the 11^th postoperative day on enteral feeds. The infant was thriving on follow-up. Conclusion: NEC may be a possible manifestation of MIS-N.

Background: Chylomicron retention disease (CRD), or Anderson disease, is included in the familial hypocholesterolemia syndromes. Blockade of transport of chylomicron from the endoplasmic reticulum to the Golgi apparatus at the cellular level results in a total absence of chylomicron and apolipoprotein B-48 in the blood circulation following a fat meal. This is associated with a deficiency in liposoluble vitamins and essential fatty acids. Clinical Description: We report the clinical, laboratory, and histological details of a 7-month-old boy who presented with recurrent vomiting, steatorrhea, abdominal distension, and failure to thrive since early infancy. On examination, he had severe acute malnutrition, pallor, dry skin, and hepatomegaly. Management and Outcome: Investigations revealed anemia, normal liver function test, amylase, and hypocholesterolemia. Endoscopy showed fat-laden duodenal mucosa with inflammation and vacuolization of the enterocytes. This prompted genetic testing for CRD which was confirmed by a homozygous deletion encompassing exonic regions of 3–7 of SAR1B gene on chromosome 5 [c.(178 + 1_179-1)_ * 1_]. Our patient was treated with a low-fat diet, allowing only essential fatty acids, and supplementation with fat-soluble vitamins. There was a gradual improvement in weight gain. Conclusion: Common fat malabsorption disorders presenting in childhood have significant failure to thrive. CRD should be suspected in infants with early-onset steatorrhea, if a typical blood lipid profile and endoscopy/biopsy findings are seen. CRD is confirmed by the detection of a mutation in the SAR1B gene.

Background: Morbid obesity is a growing concern among children and adolescents, and is complicated by multitude of morbidities such as diabetes, hypertension, metabolic syndrome, and sleep disturbances. Obesity-related hypertension is a distinct phenotype in children and adolescents and needs extensive evaluation to look for underlying etiology. Clinical Description: We report a case of acute nephritic syndrome who presented in hypertensive emergency, was found to have morbid obesity, evaluated and diagnosed as Prader–Willi syndrome with metabolic syndrome and obstructive sleep apnea (OSA). After initial stabilization, relevant blood investigations and urinalysis confirmed the diagnosis of poststreptococcal glomerulonephritis. A carefully planned evaluation identified multiple morbidities of severe obesity and determinants for the chronic hypertension. Management: The morbid obesity necessitated a thorough evaluation for etiology and complications. The child was managed for hypertensive emergency and started on multiple anti-hypertensives. The identification and management of OSA led to better control of hypertension. A holistic plan was formulated to address other medical issues including the metabolic syndrome, deranged lipid profile, impaired social cognition, and behavioral issues. Conclusion: Obesity-related chronic hypertension was unveiled in our patient by an acute hypertensive emergency. This case underscores the importance of screening for hypertension in chronic conditions such as obesity and sleep-disordered breathing at every clinical encounter and also the need for a holistic multidisciplinary approach for managing morbid obesity.

Background: Krabbe's disease is a neurodegenerative condition caused by a deficiency of a lysosomal enzyme, galactocerebrosidase (GALC), found mainly in the brain. There are four variants based on the age of onset: Infantile, late infantile, juvenile, and adult. Hematopoietic stem cell transplants can be curative as the GALC-positive donor cells migrate to the brain and provide GALC, thus correcting the deficiency. However, this is most effective when performed in the asymptomatic or mildly symptomatic phase. Maximum experience is in infantile-onset disease. The types of transplants usually used are matched sibling donor transplant or umbilical cord blood transplant. Clinical Description: A 5-year-old girl, the only child of a nonconsanguineous marriage, presented with complaints of frequent falls and progressive visual deterioration for 2 months. After evaluation, the clinical phenotype was ascertained to be that of a juvenile-onset (>5 years) neurodegenerative disorder with neuro-axis involvement of the brain (predominantly, white motor involvement-because of gait abnormalities and visual involvement) and absence of organomegaly or any other systemic involvement. Krabbe's disease was suspected. Supportive evidence was found on neuroimaging and confirmed by a homozygous mutation in the GALC gene that was consistent with Krabbe's disease. Management: The patient was treated with a matched unrelated bone marrow transplant, a modality that is generally not used in the management of Krabbe's disease. The clinical, neurophysiological, and neuroradiological profiles are compared during a 2-year follow-up. Currently, 2 years' posttransplant, she has not deteriorated further neurologically, and though legally blind is attending a special school for the visually impaired and performing most activities of daily living independently. Conclusion: Early matched unrelated donor transplant can be beneficial in juvenile-onset Krabbe's disease.

Background: Childhood vasculitis is a heterogeneous disorder, characterized by inflammation of the blood vessel walls. Multiple organs and/or tissues are affected, either simultaneously or successively. Vascular neuropathy occurs when the vasa nervorum is affected. Presentation includes mononeuritis multiplex, acute motor/motor-sensory axonal neuropathy, pure sensory neuropathy, and chronic inflammatory demyelinating polyneuropathy. Making a diagnosis is a challenge when neurological manifestations appear for the first time or are isolated. Clinical Description: A 12-year-old girl presented with acute pain and progressive weakness of both lower limbs for 12 days, followed by diffuse abdominal pain and low-grade fever. Salient neurological findings were diminished power and hyporeflexia in all limbs. Guillain–Barre syndrome was suspected in view of symmetric ascending paralysis and a suggestive nerve conduction study. The child had neutrophilic leukocytosis but sterile cultures. The successive development of inflammatory demyelinating polyneuropathy, persistent fever, vasculitic phenomena (hypertension, severe myalgia, rashes, multiple infarcts, acute renal cortical necrosis, and gangrene of the digit), and elevated acute-phase reactants was suggestive of a multisystemic small-vessel and medium-sized vasculitis syndrome, such as polyarteritis nodosa (PAN). A diagnosis of PAN was established based on the satisfaction of clinical criteria. Management: The patient was administered pulse methylprednisolone and oral steroids, with which there was a dramatic recovery. Monthly cyclophosphamide was continued in view of major systemic involvement. Conclusion: Early recognition and management of childhood vasculitis syndrome is associated with good outcomes.

Background: Diabetes insipidus (DI) is a disorder of water homeostasis due to insufficient production or inappropriate action of vasopressin. Central DI (CDI) develops due to intracranial causes such as hypoxic–ischemic encephalopathy, meningitis, and intraventricular hemorrhage. Manifestations such as polyuria, polydipsia, and irritability may not be obvious in preterm infants, resulting in delayed recognition and difficulty in establishing diagnosis. Clinical Description: A 1.4 kg preterm girl delivered by cesarean section for a significant nonstress test (but normal Apgar scores) was admitted for very low birth weight and preterm care. Initial clinical examination was normal, and the baby remained euglycemic. The neonate developed shock and fever on the 3^rd day of life without any apparent cause. Management: DI was suspected on identification of hypernatremia (150 mEq/L) and polyuria (9 mL/kg/h). The urine osmolality was low (62.54 mOsmol/kg), despite high serum osmolality (312 mOsmol/kg) confirming the diagnosis. An increase in urine osmolality by >50% following oral desmopressin (5 μg/kg/day) suggested CDI. This was continued until the baby became asymptomatic and urine/serum osmolality normalized. A trial of discontinuation of desmopressin did not lead to recurrence of symptoms. Magnetic resonance imaging brain showed features of subacute hypoxic insult and absent posterior pituitary bright spot. After 7 months of follow-up, she is asymptomatic without any treatment, and her growth and development are age appropriate. Conclusion: A high index of suspicion of CDI should be kept in neonates presenting with unexplained shock, fever, hypernatremia, and polyuria.

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially life-threatening, drug-induced hypersensitivity reaction that includes skin eruption, hematologic abnormalities, lymphadenopathy, and internal organ involvement. Clinical Description: An 11-year-old boy presented with high-grade intermittent fever and generalized rash for 7 days. He was started on phenytoin 1 month back. On presentation, the child was sick looking with 104°F fever, tachypnea, tachycardia, flushed with bounding pulses, and generalized edema suggestive of septic shock. Distinct diffuse erythematous, maculopapular rash with normal mucosae was noted all over the body with palmar and plantar erythema associated with hepatomegaly and ascites. Investigations showed eosinophilia. Management: The child was managed conservatively for septic shock, followed by withdrawing phenytoin and giving a pulse dose of methylprednisolone, followed by oral prednisolone. Conclusion: In children presenting with prolonged fever and rash with septic shock, DRESS syndrome should be considered differential diagnosis. A strong clinical suspicion and appropriate lab investigations is cornerstone of diagnosis.

Background: Gastrointestinal (GI) duplication is defined as a spherical structure with a muscular coat and is lined by a mucous membrane. It is a rare congenital anomaly. Clinical Description: A preterm baby born, delivered at 31 weeks, was diagnosed with respiratory distress syndrome and managed as per hospital protocol. While being weaned off from nasal continuous positive airway pressure, feeding was started. He developed vomiting and epigastric distension within 6 h. Management: The baby was investigated for the cause, and an early-onset sepsis was excluded. X-ray abdomen showed distended stomach and gas shadows in the bowel loops. Ultrasound did not reveal any gastric outlet obstruction, but significant gaseous distension of the stomach prompted us to make a dye study of the upper GI tract, which revealed cystic outpouching of the stomach that communicated with the gastric lumen. Similar findings were seen on computed tomographic scanning. Exploratory laparotomy performed revealed a large cyst communicating with the stomach at the lesser curvature. This was dissected out entirely from the margin of the stomach. Histopathology revealed highly congested cyst wall with an inner lining of gastric epithelium and gastric glands and an outer smooth muscle coat, confirming a gastric duplication cyst. Conclusion: Gastric duplication should be considered as a differential in newborns with feed intolerance, epigastric distension, and significant distension of the stomach. Although serial radiological investigations provide supportive evidence for this condition, the diagnostic confirmation is obtained by gross inspection and histopathology. In view of high risk of malignant transformation, surgical resection of the entire cyst remains the most definitive management.

Background: Beckwith–Wiedemann syndrome (BWS) is the most common genetic overgrowth syndrome characterized by the triad of macroglossia, macrosomia, and abdominal wall defects. Clinical Description: We report the case of a term baby girl who was born with mesoaxial polydactyly of her left foot. There were no significant antenatal events or exposure to teratogens, although a single umbilical artery (SUA) had been detected on antenatal ultrasonography. There was no evidence of in utero growth retardation. The birth weight was 3.3 kg and the perinatal transition was uneventful. The general physical and systemic examination was otherwise remarkable. Targeted search for concealed major anomalies was negative and the baby was discharged as nonsyndromic polydactyly, emphasizing the need for regular vigilant surveillance on follow-up. At 6 weeks, significant hypertrophy of the left lower limb was noted. This led the direction of evaluation toward lateralized overgrowth syndromes. Management: The application of the diagnostic algorithm prompted us to order first-tier genetic testing by methylation-specific multiplex ligation-dependent probe amplification assay. This identified aberrant DNA methylation in the chromosome 11p15 region, establishing the diagnosis of BWS. SUA and polydactyly have not been reported in combination in BWS earlier. Conclusions: Neonates with minor anomalies should always have a detailed physical examination at birth and be actively evaluated for major concealed anomalies. Since many clinical manifestations become apparent with age, it is vital that affected babies be kept under close surveillance. A rationale, individualized, step-wise approach with multidisciplinary teamwork helps in establishing the diagnosis in infants with dysmorphic features.