Clinical Spectrum of Monogenic Infantile-Onset Inflammatory Bowel Disease.

Very-early-onset IBD and infantile-onset IBD is extremely rare in children. There is paucity of data with regards to clinical profile and outcome of children with infantile-onset IBD from India. The clinicolaboratory profile, molecular genetic testing and treatment details of 8 children diagnosed with monogenic infantile-onset IBD during 2015-2020 is described here. The median age at onset of symptoms was 3 mo. Sibling death and consanguinity were noted in 4 (50%) each respectively. Diarrhea was the presentation in all (100%) and hematochezia in 5 (62%). Colonic ulcers on colonosopy was seen in 7 infants. The common mutation identified was IL-10R gene in 3 (42%) and LRBA gene mutation in 2 (25%). HSCT was done in 4 children and the rest were managed conservatively. Although there was no mortality in this series, two children (25%) were lost for follow-up.

Correction to: Clinical Spectrum of Inherited Disorders of Metabolism.

In Introduction, 4th line "In India, the reported prevalance of IEM is 1 in 2497 newborns [2] although the true pan India prevalence still remains unknown [3]".

Clinical Spectrum of Inherited Disorders of Metabolism.

OBJECTIVE: To study the clinical profile and outcome of children with Inborn errors of metabolism. METHODS: Thirty one newly diagnosed children with Inborn errors of metabolism over a 1 y period were studied for their relevant clinical, biochemical, diagnosis, treatment and follow-up details. RESULTS: Inborn errors of metabolism accounted for 2% of hospital admissions. Sixty five percent were born to parents of consanguineous marriage. Of the 31 children with Inborn errors of metabolism, 16 (51%) had lysosomal storage disorders, 8 (26%) had disorders of amino acid metabolism, 2 (6%) each had disorders of carbohydrate and bile acid metabolism, 1 (3%) each had disorders of fatty acid oxidation, mitochondrial and peroxisome metabolism. Acrodermatitis dysmetabolica, as a complication was observed in one child and the overall mortality rate in this series was 10%. CONCLUSIONS: Lysosomal storage disorders constituted the majority of Inborn errors of metabolism in this series and amino acidopathies/organic acidemias were successfully treated with special formulas.

Mutational spectrum and identification of five novel mutations in G6PC1 gene from a cohort of Glycogen Storage Disease Type 1a.

BACKGROUND: Glycogen storage disease type-1a is an inherited, autosomal recessive disorder caused by mutations in G6PC1 gene leading to deficiency of glucose-6-phosphatase-α specifically in the liver/kidney/intestine. PATIENTS AND METHODS: DNA of six unrelated Indian GSD-1a patients were screened for mutations in the entire coding region of G6PC1 gene followed by direct DNA sequencing and functional was tested using glucose-6-phosphatase assay. RESULTS: Mutational screening of GSD-1a patients identified five novel mutations, viz., 1) p.V99Cfs*3, 2) p.G125R, 3) IVS1-2A > T, 4) IVS3 + 39G > A and 5) IVS3 + 42G > A along with three previously reported mutations p.G118D, p.R149Q and p.A331V. Interestingly, each of the p.V99Cfs*3, IVS1-2A > T and p.G118D mutations are identified in two unrelated GSD-1a cases. Further allelic distribution of p.V99Cfs*3 and p.A331V mutations were confirmed by RFLP analysis, consistent with autosomal recessive inheritance. Functional characterization revealed that glucose-6-phosphatase activity was completely abrogated with the mutant proteins p.G125R, p.R149Q, p.G118D, p.A331V and p.V99Cfs*3 than wild-type. However, no significant changes were observed in the expression of mutant constructs at transcription and translation level. CONCLUSION: Five novel mutations, p.V99Cfs*3, p.G125R, IVS1-2A > T, IVS3 + 39G > A and IVS3 + 42G > A are reported first time to cause GSD-1a among Indian ethnicity and are not yet reported elsewhere, suggesting separate ethnic founder effects for some mutations among Indian ethnicity.

Bone Mineral Content and Density in Indian Children with Congenital Adrenal Hyperplasia.

OBJECTIVE: To study the bone mineral content and density in children with congenital adrenal hyperplasia (CAH). METHODS: 35 children with congenital adrenal hyperplasia and 35 healthy controls. Bone mineral content and density were studied by Dual Energy X-ray absorptiometry. RESULTS: The mean (SD) of lumbar spine bone mineral density (g/cm2) [0.590 (0.100) vs 0.589 (0.088) (P=0.97)], total Body less head bone mineral density (g/cm2) [0.536 (0.090) vs 0.548 (0.111) (P=0.64)], lumbar spine bone mineral content (g) [29.85 (27.63) vs 31.03 (29.19) (P=0.86)], and total body less head bone mineral content (g) [254.27 (281.25) vs 273.07 (330.71) (P=0.79)] were not different between children with CAH and controls, respectively. CONCLUSIONS: Bone mineral density and content in children with congenital adrenal hyperplasia are maintained in the normal range.

Clinical profile and outcome of children with scrub typhus from Chennai, South India.

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. We prospectively studied the clinico-laboratory profile and outcome of 358 children aged 1 day to 18 years diagnosed with scrub typhus from Chennai, South India. All children (100%) had fever. Eschar was seen in 67%. All children were treated with oral doxycycline and those with complications were treated with intravenous chloramphenicol/azithromycin. Rapid defervescence (within 48 h) after initiation of doxycline was seen in 306 (85%) and 52 (14.5%) developed complications. Multivariate logistic regression analysis revealed that children who had an elevated aspartate amino transferase (> 120 IU/L) and the presence of thrombocytopenia (platelet count less than 1 lac cells/mm3) at admission had high risk of developing complications. The overall mortality rate in this series was 0.8%. CONCLUSION: Our 4-year study highlights the clinico-laboratory profile of Scrub typhus in children from Chennai, South India. Early recognition and prompt treatment reduces the complication and mortality. What is Known: • Scrub typhus is endemic to tsutsugamushi triangle, a geographical triangle extending from northern Japan in the east to Pakistan and Afghanistan in the west and northern Australia in the south. • There is paucity of data regarding its clinico-laboratory profile in neonates as well as its predictors of outcome. What is New: • Children who had an elevated AST and the presence of thrombocytopenia at admission had high risk of developing complications.

A 6-year-old boy with Wilson disease-A diagnostic dilemma.

A 6-year-old boy presented with 2 months history of progressive abdominal distension and jaundice. He was deeply icteric with ascites, hepatosplenomegaly, hyperbilirubinemia, raised transaminases, and coagulopathy. Viral markers and slit lamp examination for Kayser-Fleischer ring were negative. Serum ceruloplasmin and 24-h urinary copper post-D-pencillamine challenge were normal. Anti-smooth muscle antibody was positive 1:20, and liver biopsy showed micronodular cirrhosis with abundant Mallory hyaline and stainable copper deposits. The liver histology was indicative of Indian childhood cirrhosis, whereas the presence of autoantibodies, elevated transaminases, and increased globulin was suggestive of autoimmune hepatitis. Gene studies identified p.R969Q mutation in ATP7B gene, which solved the dilemma and confirmed the diagnosis of Wilson disease (WD). We report a clinicopathological conference of this boy to highlight the challenges faced by pediatricians in the diagnosis of Wilson disease. ᅟ.

Neonatal Diabetes: A Case Series.

BACKGROUND: Neonatal diabetes mellitusis a rare disorder with an incidence of 1 in 2,60,000 live births. METHODS: Retrospective analysis of clinical and genetic profile of children admitted with neonatal diabetes mellitus in a tertiary-care hospital in Chennai, India over 11 years. RESULTS: Ten children were diagnosed with neonatal diabetes of whom 9 had permanent neonatal diabetes mellitus. The age range at onset was from 3 days- 5 months. Of the 9 children, KCNJ11 gene mutation was positive in one, and ABCC 8 and INS gene mutation in two children each. Children with KCNJ11 and ABCC 8 gene mutations were switched over to oral sulfonyl urea therapy. CONCLUSION: Few genotypes causing NDM can be managed effectively with oral sulfonyl ureas.

Correlation of Bone Mineral Parameters with Anthropometric Measurements and the Effect of Glucocorticoids on Bone Mineral Parameters in Congenital Adrenal Hyperplasia.

OBJECTIVE: To correlate the bone mineral parameters [bone mineral content (BMC) and bone mineral density (BMD)] using Dual energy X ray Absorptiometry (DXA) scan with anthropometric measurements and to study the effect of glucocorticoid therapy on BMC/BMD in children with Congenital adrenal hyperplasia (CAH). METHODS: A cross-sectional study was carried out in the Pediatric Endocrinology unit from January 2012 through March 2013 at Kanchi Kamakoti CHILDS Trust hospital, Chennai. Thirteen CAH children aged 0-132 mo with classic salt wasting due to 21 hydroxylase deficiency were included in the study. All children were treated with T.hydrocortisone @10-15 mg/m(2)/d twice daily and T. fludrocortisone 50 µg once daily orally at the time of enrollment into the study. The duration of glucocorticoid (hydrocortisone) treatment from the date of diagnosis till the time of enrollment into the study was noted and categorized as children receiving < 5 and > 5 y of glucocorticoid therapy. None received Vitamin D/calcium supplementation at the time of enrollment. BMC and areal BMD for the lumbar spine and total body less head (TBLH) were measured with Lunar DXA machine. RESULTS: The mean height, weight and BMI of children were 87.3 ± 33 cm, 13.49 ± 11.2 kg and 14 ± 4.07 kg/m(2) respectively. TBLH BMC was 369.14 ± 312.18 g and TBLH BMD was 0.63 ± 0.11 g/cm(2). There was a significant correlation between height and total body less head BMC/BMD in the index series [P < 0.05, significant]. The TBLH and spine BMD were also assessed with regards to the duration of glucocorticoid therapy and it has been observed that TBLH and spine BMD decreased with increased duration of steroid therapy (p < 0.05, significant). CONCLUSIONS: In the absence of normative data or z scores, BMC/BMD correlates well with height for age. Children who received more than 5 y of glucocorticoid treatment had lower TBLH and spine BMD scores and hence, calcium and Vitamin D supplementation should be considered.

Partial internal biliary diversion: a solution for intractable pruritus in progressive familial intrahepatic cholestasis type 1.

Biliary diversion offers a potential option for intractable pruritus in children with chronic cholestatic disorders. Progressive familial intrahepatic cholestasis (PFIC) is an inherited disorder of impaired bile acid transport and excretion, which presents with jaundice and pruritus in the first few months of life and progresses to cirrhosis by infancy or adolescence. We report a child with PFIC type 1 who underwent internal biliary diversion for intractable pruritus and was relieved of his symptoms.

Profile of typhoid fever in children from a tertiary care hospital in Chennai-South India.

AIM: To study the clinical profile and outcome of hospitalized children with typhoid fever. MATERIALS AND METHODS: A retrospective study was conducted in a private tertiary care children's hospital over a 3 year period. RESULTS: A total of 316 children (7 in every 1000 admissions) were diagnosed to have typhoid fever during this period. More than one third were aged between 5 and 10 years and most cases (38%) clustered around the months of January to April. Around 59% of children in our series were unimmunised against typhoid. Eosinopenia was seen in 72 %. There was a significant increase in NARST (p < 0.001). Predictors of severity in this study were increased AST levels, eosinopenia and isolation of NARST. CONCLUSION: Public health interventions to minimize human carrier contact, improved personal hygienic measures including health care behavior strategies, typhoid vaccination and rational antibiotic selection based on sensitivity pattern to prevent resistance will help to reduce the morbidity and mortality of this global health problem.

Kawasaki disease mimicking retropharyngeal abscess.

Kawasaki disease is an acute, self-limiting febrile mucocutaneous vasculitis of infants and young children. Retropharyngeal lymphadenopathy is a rare presentation of Kawasaki disease. We present a case of Kawasaki disease mimicking a retropharyngeal abscess, with upper airway obstruction resulting in delayed diagnosis.

Clinical profile and outcome of diabetic ketoacidosis in children.

UNLABELLED: BACKGROUND. There is little information on the clinical profile and outcome of children with diabetic ketoacidosis in India. We analysed the data of children managed by us at a tertiary care hospital. METHODS. We retrospectively analysed the case records of 21 children (13 boys and 8 girls) with diabetic ketoacidosis admitted to our hospital from January 2004 to August 2008. They were managed using a standard protocol including intravenous fluids and insulin infusion. Blood glucose, serum electrolytes, blood urea, arterial blood gases and urinary ketones were monitored at regular intervals. The outcomes were assessed. RESULTS: The median age at presentation was 8 years and 17 children (80%) were detected to have diabetes mellitus at the time of presentation. Twelve children (57%) presented with severe diabetic ketoacidosis. Polyuria with polydipsia was the commonest clinical presentation (17). All of them had elevated HbA1C levels. The average length of stay in the paediatric intensive care unit was 2.9 days. The median time for the arterial blood gases to become normal was 19 hours and for urinary ketones to become non-detectable was 28 hours. None of the children received bicarbonate and there were no complications or mortality. All the children were doing well on follow up at 3 months. CONCLUSION; The outcome of active management of diabetic ketoacidosis in children is rewarding. The use of a standard protocol for management was associated with no complications or mortality in our series.