Identification of a novel homozygous intron 3 splice site (A>T) mutation in the ARG1 gene in cerebral palsy pediatric cases from Odisha, India.

BACKGROUND: Arginase enzyme is essential for the catalysis of the last step of the urea cycle, resulting in the conversion of L-arginine to L-ornithine and urea. Arginase deficiency could lead to hyperarginemia, an autosomal recessive disorder of the urea cycle that could result in developmental manifestations after the first year of life, followed by gradually progressive atonic cerebral palsy, spastic quadriplegia, and mental decline. ARG1 mutations have been reported in hyperarginemia patients of Western countries because they exhibited reduced arginase activity. Hence, it is important to assess ARG1 mutations in cerebral palsy cases with hyperarginemia in different populations. METHODS AND RESULTS: This study involved two unrelated pediatric patients from two non-consanguineous East Indian families, exhibiting a range of manifestations, including hypotonia of all limbs, mental retardation, and multiple episodes of seizure. The onset of the disease ranged from 1 to 3 years of age. Hyperammonemia (> 250 micromoles) and serum hyperarginemia (> 350 micromoles) were observed in both the patients. Whole-genome sequencing, followed by Sanger sequencing of both the patients confirmed the presence of a homozygous 3' splice site variation in intron 3 of the ARG1 gene (chr6: g.131902357A>T) that affects the invariant AG acceptor splice site of exon 4 (c.330-2A>T; ENST00000356962.2). CONCLUSION: The study reported the identification of a novel ARG1 mutation in two different unrelated pediatric cases from Odisha, India associated with hyperarginemia. The pathogenicity of the mutation was robustly supported by the clinical phenotype, complete co-segregation with the disease, and biochemical observations.

Scrub Typhus in Paediatric Age Group at a Tertiary Care Centre of Eastern India: Clinical, Biochemical Profile and Complications.

Background: Scrub typhus is a reemerging zoonosis, which presents as acute febrile illness. Very few paediatric prospective studies on this disease are reported from Eastern India. This prospective observational study was carried out to study the clinical presentation, diagnosis, complications and immediate outcome of Scrub typhus in paediatric population in a tertiary care hospital from Eastern India. Material and Methods: Totally 209 cases between 1 month and 18 years of age were included. Clinical manifestations, laboratory parameters and immediate outcome of all patients were recorded. All the data were collected and plotted in Microsoft Excel master chart. Continuous data were presented as mean ± standard deviation (SD) and categorical data as frequency and percentage. All the data analysis was performed using statistical software IBM Statistical Package for the Social Sciences (SPSS) version 20.0. Results: Highest number of cases (41.1%) were found between 1 year and 5 years age group. Fever was the presenting complaint in all cases. Other common symptoms were cough (34%), pain abdomen (23.4%), vomiting (23%), seizure (11.5%) and altered sensorium (9.6%). Hepatomegaly was found in 56.5% and splenomegaly in 39.7% cases. Eschar was found in 27.3% cases. C-reactive protein was elevated (>10 mg/L) in 93.3% children. Other complications were pneumonitis (20.6%), meningoencephalitis (12.4%), septic shock (8.6%), acute respiratory distress syndrome (5.7%), myocarditis (4.8%) and acute kidney injury (4.3%). Mortality was low (1%). Conclusion: Scrub typhus is not uncommon in paediatric population and it must be considered as a close differential diagnosis of any acute febrile illness even when classical clinical presentations are not found. Early treatment results in favourable outcome.