New insights from the genetic work-up in early onset nephrotic syndrome: report from a registry in western India.

BACKGROUND: Eighty-five percent of infants with congenital nephrotic syndrome (CNS) and 66% with infantile NS (INS) are likely to have a monogenic etiology. There exists a significant genetic variability between different regions and ethnic groups. This study aimed to determine the genetic defects in children with CNS and INS by establishing a registry in western India. METHODS: In this cross-sectional study, pediatric nephrologists from 13 private and government institutions shared relevant clinical data and details of the genetic evaluation of children presenting with NS within the first year of life. RESULTS: The median age at presentation was 9 months (range 1-23, IQR 3-13 months), history of consanguinity between parents existed in 14 patients (34%), family history of similar illness in 6 (15%), and extra-renal manifestations in 17 (41%). Twenty-five (61%) were confirmed to have a monogenic etiology. NPHS1 gene was the most implicated (9/25) followed by PLCE1 (5/25). There were 12 variants of uncertain significance (VUS) involving 10 genes (10/25, 40%), and no definite genetic abnormality was found in 4 (25%). A re-analysis of these VUS attempted 2-3 years later facilitated reclassification of 7/12 (58%); increasing the diagnostic yield from 61 to 68.2%. CONCLUSIONS: Consistent with worldwide data, variants in NPHS1 gene were the most common cause of NS in infancy; however, PLCE1 was implicated more frequently in our cohort. NUP93 and COL4A3 were reported in early onset NS for the first time. Reclassification of VUS should be attempted, if feasible, since it may lead to a useful revision of diagnosis.

Prevalence and subtypes of hypertension in normal-weight and obese Indian adolescents: a cross-sectional study.

This cross-sectional study examined the prevalence, stages, subtypes of hypertension, and the associated risk factors in adolescent school children in Western India. We screened 2,644 adolescents, from 10 different private and government schools in urban and rural areas for hypertension, as defined by the 2017 Clinical Practice Guidelines. The association of stages and subtypes with age, gender, body mass index, type of school, and place of residence was analysed. 197 children (7.5%) had hypertension; 170 (6.4%) had stage I, 27 (1%) had stage II and 76 (2.9%) had elevated blood pressure (EBP). The risk of EBP was higher in children > 15 years of age (p = 0.006). Compared with normal-weight children, obese, and overweight children had a higher risk of hypertension [odds ratio (OR) 9 (5.84, 13.88) and 3.77 (2.59, 5.48) respectively], whereas underweight children had a lower risk [OR 0.39 (0.16, 0.98)]. Normal-weight hypertension was seen in 5.2% and was higher in children from government schools (9.4%). Systolic-diastolic hypertension (SDH) was the most common subtype, seen in 136 (5.1%). SDH was more common in girls, in rural children, and in those with stage II hypertension. Isolated diastolic hypertension, seen in 51 (1.9%), was more common in boys, in urban children, and in those with EBP.

Effectiveness of 3-day amoxycillin vs. 5-day co-trimoxazole in the treatment of non-severe pneumonia in children aged 2-59 months of age: a multi-centric open labeled trial.

This cluster randomized, open labeled trial was conducted to compare the effectiveness of 3 days of oral amoxycillin and 5 days of co-trimoxazole treatment in terms of clinical failure in children with World Health Organization (WHO) defined non-severe pneumonia in primary health centers in rural India. Participants were children aged 2-59 months with WHO defined non-severe pneumonia, with or without wheeze, who were accessible to follow up. From seven primary health centers in each arm, 2009 cases were randomized, 993 and 1016 in treatment with amoxycillin and co-trimoxazole, respectively. Fever was present in 1247 (62.1%) and wheeze in 443 (22.1%). There was good adherence and low loss to follow-up. Clinical failure on amoxycillin and co-trimoxazole on intention to treat analysis was 137 and 97, respectively (absolute difference = 0.04, 95% confidence interval: - 0.035-0.12). We conclude that there was no difference in effectiveness of oral co-trimoxazole or amoxycillin in treating non-severe pneumonia.

Infantile nephropathic cystinosis with incomplete fanconi syndrome, hypothyroidism, hydro-uretero-nephrosis, and megacystis.

Cystinosis is an autosomal recessive lysosomal storage disorder characterized by the accumulation of the amino-acid cysteine in various organs and tissues. Infantile nephropathic cystinosis is the most severe form of the disorder. We describe the clinical features in a four and a half-year-old Indian boy with infantile nephropathic cystinosis that presented with the incomplete Fanconi syndrome, hydro-uretero-nephrosis with megacystis, and hypothyroidism.

Acute disseminated encephalomyelitis.

The authors report 6 children with the diagnosis of acute disseminated encephalomyelitis. Diagnosis was based on clinical and radiological findings. The most common presenting symptoms were fever and disturbed consciousness, followed by cranial nerve abnormalities and pyramidal signs. Brain MRI showed hyperintense signals on T2-weighted images, most commonly in the subcortical and periventricular white matter, brainstem, basal ganglia and thalamus. The lesions were bilateral, asymmetrical and highly variable in size and number. A preceding infection was present in 3 of 6 children. Early high-dose corticosteroids were given to all the patients. All patients recovered clinically. Follow-up ranged from 10 months to 2 years. No relapses were observed during this period. Early high-dose steroid therapy seems to be an effective treatment in acute disseminated encephalomyelitis.

Bilateral anotia with congenital hypothyroidism.

Bilateral anotia or microtia is known to be associated with multiple order malformations. The authors report a young infant who presented with failure to thrive and recurrent respiratory tract infections. The patient had bilaterally absent pinnae; instead small skin tags were present. He also had asymmetric crying facies and clinical evidence of hypothyroidism in the form of hoarse voice, constipation and generalized hypotonia. Thyroid function tests confirmed the diagnosis of hypothyroidism.

Atypical hemolytic uremic syndrome with membranoproliferative glomerulonephritis.

Atypical hemolytic uremic syndrome (aHUS) associated with membranoproliferative glomerulonephritis (MPGN) is an uncommon clinical presentation, especially in children. We report a 8-year-old-boy who presented like aHUS but the kidney biopsy showed MPGN type 1.

Distal renal tubular acidosis in a child with HIV infection.

Renal tubular acidosis (RTA) is not uncommon in HIV-infected children with advanced disease, and has been described mainly due to nephrotoxic anti-retroviral therapy and in association with prophylaxis or treatment of Pneumocystis carinii pneumonia with co-trimoxazole. We describe an 8-year-old boy, newly diagnosed to have HIV infection, who presented with distal RTA. There were no features of chronic RTA in the form of rickets or nephrocalcinosis, making an inherited form unlikely.

Does 3-day course of oral amoxycillin benefit children of non-severe pneumonia with wheeze: a multicentric randomised controlled trial.

BACKGROUND: WHO-defined pneumonias, treated with antibiotics, are responsible for a significant proportion of childhood morbidity and mortality in the developing countries. Since substantial proportion pneumonias have a viral etiology, where children are more likely to present with wheeze, there is a concern that currently antibiotics are being over-prescribed for it. Hence the current trial was conducted with the objective to show the therapeutic equivalence of two treatments (placebo and amoxycillin) for children presenting with non-severe pneumonia with wheeze, who have persistent fast breathing after nebulisation with salbutamol, and have normal chest radiograph. METHODOLOGY: This multi-centric, randomised placebo controlled double blind clinical trial intended to investigate equivalent efficacy of placebo and amoxicillin and was conducted in ambulatory care settings in eight government hospitals in India. Participants were children aged 2-59 months of age, who received either oral amoxycillin (31-54 mg/Kg/day, in three divided doses for three days) or placebo, and standard bronchodilator therapy. Primary outcome was clinical failure on or before day- 4. PRINCIPAL FINDINGS: We randomized 836 cases in placebo and 835 in amoxycillin group. Clinical failures occurred in 201 (24.0%) on placebo and 166 (19.9%) on amoxycillin (risk difference 4.2% in favour of antibiotic, 95% CI: 0.2 to 8.1). Adherence for both placebo and amoxycillin was >96% and 98.9% subjects were followed up on day- 4. Clinical failure was associated with (i) placebo treatment (adjusted OR = 1.28, 95% CI: 1.01 to1.62), (ii) excess respiratory rate of >10 breaths per minute (adjusted OR = 1.51, 95% CI: 1.19, 1.92), (iii) vomiting at enrolment (adjusted OR = 1.49, 95% CI: 1.13, 1.96), (iv) history of use of broncho-dilators (adjusted OR = 1.71, 95% CI: 1.30, 2.24) and (v) non-adherence (adjusted OR = 8.06, 95% CI: 4.36, 14.92). CONCLUSIONS: Treating children with non-severe pneumonia and wheeze with a placebo is not equivalent to treatment with oral amoxycillin. TRIAL REGISTRATION: ClinicalTrials.gov NCT00407394.

Fatal thyrotoxic periodic paralysis with normokalemia.

We present a 10-year-old girl who presented to our emergency services with difficulty in breathing of 2-days duration and progressive weakness of a month's duration. In a previous admission elsewhere, she had not been detected to have hyperthyroidism or electrolyte abnormalities. On admission, the child was in hypercapnic respiratory failure with tachycardia and hepatomegaly. A small goiter as well as signs of thyrotoxicosis were present. Laboratory investigations showed anemia, mildly elevated liver enzymes and serum potassium of 4.8mEq/L. Despite intubation and ventilation and other supportive management including propranolol, the patient could not be saved. Post-mortem biopsy of the thyroid showed diffuse hyperplasia of the follicles and muscles showed evidence of thyroid myopathy.

Congenital paraesophageal hernia presenting with severe gastroesophageal reflux.

Paraesophageal hernia in children is relatively rare entity. These children usually present with recurrent respiratory tract infection or vague GI symptoms. An 11 year female presented with episodic vomiting, heartburn and features of hypocalcemic tetany. Investigations revealed right paraesophageal hernia. Reduction of the contents and repair of the defect with fundoplication was done. Patient is asymptomatic on follow-up.

Exchange transfusion in children with severe falciparum malaria and heavy parasitaemia.

While exchange transfusion has been advocated as an adjunctive treatment in severe falciparum malaria complicated by heavy parasitaemia, its role in severe life-threatening disease refractory to standard life support measures is less well recognised. We describe four children with severe falciparum malaria, multi-system involvement and heavy parasitaemia in whom we undertook exchange transfusion because of their deteriorating clinical condition despite antimalarials and supportive therapy. All patients received quinine (one also received artesunate). All patients improved dramatically following the procedure, with subsequent complete clinical recovery.