Case Series of Ethylmalonic Encephalopathy from Southern India.

Ethylmalonic encephalopathy is a rare neurometabolic disorder with central nervous system involvement and vasculopathy. It is presented in infancy with developmental delay, acrocyanosis, petechiae, chronic diarrhea, and early death. This was a retrospective study of confirmed cases of ethylmalonic aciduria from a tertiary care hospital over a period of 5 years from January 2015 to December 2020. Case details including analysis of clinical history, investigations, and outcomes are presented. Of six cases, male-to-female ratio was 4:2. Mean age of presentation was 35.5 months (range: 14-83 months). Consanguinity, global developmental delay, failure to thrive, skin rashes, microcephaly, hypotonia, and exaggerated deep tendon reflexes were observed in all cases. Chronic diarrhea was presented in five cases. The serum levels of C4 carnitine and urinary levels of ethylmalonic acid were increased in all cases. Magnetic resonance imaging (MRI) of the brain showed heterogenous bilateral symmetrical changes in the basal ganglia in five cases, and in one case, MRI could not be done. Genetic testing in two cases showed a homozygous variant in ETHE1 gene. Four children died, while the other two cases showed a decreased in recurrent encephalopathies and diarrhea after starting metronidazole. All children had global developmental delay, failure to thrive, skin rashes, central hypotonia, increased C4 carnitine levels in the serum, and increased ethylmalonic acid in the urine. Chronic diarrhea, acrocyanosis, and basal ganglia change in the MRI of the brain also give important clues for diagnosis. Metronidazole is useful in preventing recurrent episodes of encephalopathy.

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.

Assessment of neurological sequelae and new-onset symptoms in the long-term follow-up of paediatric Guillain-Barre syndrome: A longitudinal study from India.

BACKGROUND: Guillain-Barre syndrome (GBS) is the commonest cause of acute flaccid paralysis in children. There is a paucity of studies that assess the long-term outcome of paediatric GBS. AIM: To assess the frequency of neurological sequelae and the new-onset symptoms in the long-term follow-up of paediatric GBS and to identify the risk factors associated with them. METHODS: This longitudinal study involved 78 children with GBS treated between January 2015 and 2021. The parents of those children were contacted to visit the hospital for a detailed neurological examination and to look for new-onset symptoms after the initial treatment for GBS. RESULTS: Of the 78 children, acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, and acute motor-sensory axonal neuropathy variants were observed in 30 (38.5%), 27 (34.6%) and 11 (14.1%) children, respectively. The median (interquartile range (IQR)) duration of follow-up was 3 (2, 4.5) years. The median (IQR) time to independent ambulation was 30 (13.5, 105) days. The neurological sequelae were found in 22 (28.2%) children. GBS disability score at admission (odds ratio (OR) = 4.6; 95% confidence interval (CI): 1.1-19.8; P = 0.04) and axonal variant of GBS (OR = 4.1; 95% CI: 1.5-20.8; P = 0.04) were found to be independent predictors of neurologic sequelae. A total of 28 children experienced new-onset symptoms after GBS, with frequent falls while running and fatigue being the predominant symptoms. Those children with demyelinating variant achieved independent ambulation earlier than the axonal group on survival analysis (log-rank P value = 0.04). CONCLUSION: The presence of neurological sequelae and new-onset symptoms were found in 28.2 and 35% of the GBS children, respectively. High GBS disability score at admission and axonal variant of GBS were independent predictors of neurological sequelae. Knowledge about these would help in devising a plan for rehabilitation.

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.

Neuronal Ceroid Lipofuscinosis: Clinical and Laboratory Profile in Children from Tertiary Care Centre in South India.

Neuronal ceroid Lipofuscinosis (NCL), inherited disorders of lysosomal storage disorders, constitute the most common progressive encephalopathies with an incidence of 1.3 to 7 in 100,000 live births. We reported clinical, electrophysiological, radiological, ultrastructural, and molecular genetic features of NCL. This is a retrospective review, in a tertiary care center from January 2016 to December 2019. All children with clinical features of NCL and confirmed by pathogenic mutation and/or enzyme assay were included. A total of 60 children (male:female = 3:1) were studied. The commonest type was CLN 2 (41.7%). Neuroregression, seizures, and ataxia were present in all cases. Retinal arterial attenuation was seen in 38.33% cases. Magnetic resonance imaging (MRI) brain was abnormal in all patients, thalamic and caudate nucleus atrophy common in CLN1 (62%). Electroencephalography was abnormal in all children, but photoparoxysmal response at low intermittent photic stimulation frequencies was seen in four children of CLN2. Electron microscopy done in 43 children revealed abnormal inclusions in 20 (46.52%) children. Enzyme study showed low levels in 36 (78%) out of 46 cases. Of these, 21 had low tripeptidyl peptidase and 15 had low palmitoyl protein thioesterase levels. Molecular testing done in 26 cases showed pathogenic variant in 23 (88%) cases. Infantile onset with thalamic atrophy on MRI is common in CLN1 and refractory epilepsy, visual impairment and specific EEG changes are common in CLN2. These features are helpful in selecting enzyme assay for CLN1 versus CLN2. Electron microscopy helped in the diagnosis and genetic testing in subtyping. Thus, a multimode approach played a role in the diagnosis of NCL.