Genetic Studies in Infants with Congenital Nephrotic Syndrome: A Case Series.

Information on the genetic profile of congenital nephrotic syndrome (CNS) from India is scarce. The management of CNS is largely supportive of the setting of developing countries, mainly via the administration of intravenous albumin infusions, angiotensin-converting enzyme inhibitors, and levothyroxine. Inadequate infrastructure and management facilities, including genetic analyses, further hamper the outcome. These infants may progress to end-stage renal disease, and mortality is high in infancy. Here, we report a case series of four infants (aged 14-60 days) with CNS from our center with genetic mutations (including mutations in the NPHS1 and LAMB2 genes) that were not described in previous reports from India. Although responsiveness to enalapril has been documented in anecdotal reports of NPHS1 mutations, our case series of four infants did not exhibit any response to enalapril. Our case series adds to the existing literature regarding the genetic profile of CNS in India.

Pyridoxine Therapy: Not Just the Dose, the Duration Matters Too.

Pyridoxine-dependent epilepsy (PDE) (OMIM 266100) is an autosomal recessive disorder of lysine metabolism secondary to antiquitin deficiency. The prototypical presentation is intractable neonatal seizures that do not respond to conventional antiseizure medication but are well controlled by pyridoxine supplementation. Atypical forms account for one-third of the PDE spectrum and may escape early diagnosis. The common atypical presentations include the prenatal onset of seizures, seizures onset as delayed as 3 years of age, autism, arrested hydrocephalus, and fetal ventriculomegaly. Herein, we describe a 9-month-old child with neonatal-onset refractory seizures who failed two short trials of pyridoxine therapy and was later diagnosed with PDE by molecular studies. Regardless of the therapeutic response, a prolonged course of pyridoxine therapy is justified to identify delayed responders in infants with drug-refractory epilepsy of no apparent etiology.

Neutrophil-Lymphocyte Ratio for Predicting Coronary Artery Lesions in Children With Kawasaki Disease.

BACKGROUND: Coronary artery lesions (CAL) are a specific feature of Kawasaki disease (KD), and develop during the second week of illness. This study was conducted to determine whether Neutrophil: Lymphocyte Ratio (NLR), assessed between the fourth and sixth day of fever onset in children with KD, can predict coronary artery lesion (CAL) development. METHODS: In this review of hospital records, data of patients with KD admitted at our center between January, 2016 and January, 2020 was retrieved. The patients were divided into two groups based on the presence of CAL, and clinical characteristics of patients were compared between the two groups. RESULTS: Out of the 79 patients enrolled, CAL was found in 40 (50.6%) patients and intravenous immunoglobulin (IVIg) resistance was seen in 13 (16.5%) patients. Multivariate logistic regression revealed NLR as an independent predictor of CAL [OR (95% CI) 2.0 (1.2-3.1); P<0.001], and erythrocyte sedimentation rate (ESR) [OR (95% CI) 1.03 (1.001-1.1) P=0.04], as an independent predictor of IVIg resistance. NLR ≥2.08 was 82% sensitive and 80% specific in predicting CAL. ESR ≥88 mm/h was 85% sensitive and 64% specific in predicting IVIg resistance. CONCLUSIONS: NLR is an independent predictor of CAL in KD. NLR ³2.08 done between the fourth and sixth day of fever onset may identify children with KD at risk of CAL.

Etiology, Comorbidities, and Rate of Progression of Pediatric Chronic Kidney Disease: A Cohort Study.

OBJECTIVES: To evaluate the etiology of pediatric chronic kidney disease (CKD), assess comorbidities, and identify rate of progression of CKD and its risk factors. METHODS: Children aged 2-18 y with the Kidney Disease Improving Global Outcome (KDIGO) CKD stages 2-4 were enrolled. The etiology of CKD and its comorbidities were recorded. Kaplan-Meier survival curves were used to analyze the time to progression of CKD. RESULTS: Of the 131 patients enrolled, CKD stages 2, 3a, 3b, and 4 constituted 62 (47.3%), 17 (13%), 26 (19.8%), and 26 (19.8%), respectively. At the last follow-up [at median (IQR) 24 (12, 30) mo], the number of children in CKD stages 2, 3a, 3b, 4 and 5 were 48 (36.6%), 16 (12.2%), 23 (17.6%), 28 (21.4%), and 16 (12.2%), respectively. Etiologies of CKD included obstructive uropathy [48 (36.6%)], chronic glomerular disease [19 (14.5%)], reflux nephropathy [14 (10.7%)] and cystic renal disease [11 (8.3%)]. Comorbidities during follow-up included CKD-MBD [87 (66.4%)], metabolic acidosis [95 (72.5%)], hypertension [88 (67.1%)], growth retardation [69 (52.6%)], and anemia [63 (48.1%)]. The number of patients with metabolic acidosis, hypertension, MBD and anemia in CKD stage 2 were 27 (56%), 26 (54.2%), 24 (50%), 15 (30%), respectively. The median (IQR) rate of decline in eGFR was 3.3 (2, 4.6) mL/min/1.73 m2/y. On multivariable analysis, proteinuria [hazard ratio 3.5 (95% CI 1.4, 8.8) p = 0.01] and hyperphosphatemia [hazard ratio 2.2 (95% CI 1.1, 4.3) p = 0.03] were significant predictors for progression of CKD. CONCLUSIONS: Even the earlier stages of CKD had significant comorbidities. The median decline in eGFR was 3.3 mL/min/1.73 m2/y. Proteinuria and hyperphosphatemia were the risk factors for progression of CKD.

Paradoxical upgrading reaction following treatment of disseminated tuberculosis-associated haemophagocytic lymphohistiocytosis in an infant without HIV: a case report and review of the literature.

Tuberculosis-associated haemophagocytic lymphohistiocytosis (HLH) is rare in paediatrics and can be fatal if not recognised and treated on time. A 3-month-old infant with tuberculosis and HLH is described. He was successfully treated with anti-tuberculous therapy (ATT) which comprised isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin and dexamethasone (10 mg/m2/day). On Day 28 of therapy, he developed a paradoxical upgrading reaction to ATT for which he was again treated with (oral) corticosteroids for 4 weeks. He recovered successfully and is now completely well and asymptomatic. To the best of our knowledge, this is the first case of a child having a paradoxical upgrading reaction following treatment for TB-HLH.Abbreviations ATT: anti-tuberculous therapy; CB-NAAT: cartridge-based nucleic acid amplification test; CECT: contrast-enhanced computed tomography; HLH: haemophagocytic lymphohistiocytosis; NK: natural killer, PUR: paradoxical upgrading reaction; sHLH: secondary HLH.

A rare cause of stroke in young children: minor head trauma associated with mineralising lenticulostriate angiopathy in three patients.

Acute basal ganglia infarct following minor head trauma in association with mineralisation of lenticulostriate arteries is an increasingly recognised entity in childhood stroke. Three cases with a classical history and phenotypical features of mineralising angiopathy are described. Case 1 was a 2-year-old girl who presented with acute onset hemiparesis with a same-side upper motor neuron (UMN)-type facial palsy following minor head trauma. Case 2 was a 14-month-old boy who presented with a left side hemiparesis and a left UMN-type facial nerve palsy following a minor fall. Case 3 was an 8-month-old boy who, following a fall from his cot, had a sudden-onset hemiparesis on the right side and deviation of the angle of the mouth to the left. In brain computed tomography, all three cases demonstrated characteristic basal ganglia calcification of the mineralising angiopathy. Magnetic resonance imaging of the brain demonstrated features supportive of acute infarcts in the lentiform nucleus, caudate nucleus and putamen. Two of the patients had iron deficiency anaemia with haemoglobin of 7.0 g/dL and 7.8 g/dL, respectively. On follow-up, Case 1 had mild residual weakness and the other two made a complete recovery. None of the patients had a recurrence of stroke. Basal ganglia stroke with mineralising angiopathy should be considered in toddlers presenting with sudden-onset focal neurological deficits preceded by minor head trauma.Abbreviations: ADC: apparent diffusion coefficient; CT: computed tomography; DWI: diffusion-weighted imaging; Hb: haemoglobin; IDA: iron deficiency anaemia; MRI: magnetic resonance imaging; SLV: sonographic lenticulostriate vasculopathy; SWI: susceptibility weighted imaging; UMN: upper motor neuron.

Haematohidrosis in a 12-year-old boy: blood, sweat and tears.

A 12-year-old boy presented with a 1-year history of episodes of spontaneous bleeding from multiple sites lasting for a few minutes. His medical history was unremarkable and all the episodes of bleeding began after he was separated from his aunt to whom he was very much attached. She had moved out of their home following her marriage. All haematological investigations were normal. He was diagnosed with haematohidrosis secondary to adjustment disorder, and behavioural therapy was advised and propranolol prescribed. At present he is asymptomatic and on regular follow-up.Explanations of terms used in the text: Adjustment disorder: maladaptive response to a psychosocial stressor in an individual with significant difficulty coping with a stressful psychosocial event; anxiolytics: medication that reduces anxiety; chromohydrosis: secretion of coloured sweat; haematochezia: passage of fresh blood through the anus, usually in or with stools; haematohidrosis: sweating blood; oto-erythrosis: spontaneous bleeding from the ear; otorrhagia: haemorrhage from the ear; vicarious menstruation: cyclical bleeding outside the uterine cavity during the menstrual cycle.