Sharmila B. Mukherjee

Sensitivity of the autism behavior checklist in Indian autistic children.

Objective: The autism behavior checklist (ABC) has potential utility for evaluation of autistic children in resource-poor settings. Although the original total cutoff score has been described as 67, lower cutoffs have been suggested. We evaluated the sensitivity of ABC in the diagnosis of autism in Indian children. Methods: This study was conducted over 2 years in the Child Development Clinic of a tertiary care hospital. Children diagnosed with autistic disorder as per the DSM-IV criteria were included. Children with comorbid motor, visual, and hearing deficits were excluded. Each child was evaluated using the Childhood Autism Rating Scale and ABC. Results: Fifty-one children were enrolled in the study. The mean age was 3.28 ± 1.89 years. The ratio of boys to girls was 2.2:1. The mean Childhood Autism Rating Scale score was 44.7 ± 6.22, with all children having scores in the autistic range. The mean ABC score was 72.4, with a standard deviation of 14.2. By using the originally suggested cutoff score of 67, only 40 children in this study were diagnosed with autism. When lower cutoffs were used, the sensitivity increased, with a sensitivity of 98% and a cutoff of 45. Conclusion: The ABC cutoff needs to be lowered to increase its sensitivity for diagnosis of autistic disorder.

Rosai-dorfman Disease: A Case With Lymphadenopathy and Liver Involvement

Rosai-Dorfman disease (RDD), originally described as sinus histiocytosis with massive lymphadenopathy, is a rare histiocytic proliferative disorder with a distinctive microscopic appearance. Formerly thought to be a disease process limited to lymph nodes, RDD has now been reported in many organ systems like bone, skin and soft tissue, central nervous system, eye and orbit, and upper respiratory tract. Here we report a case of RDD with hepatic involvement, which is even more rare.

INCLEN diagnostic tool for attention deficit hyperactivity disorder (INDT-ADHD): development and validation

ObjectiveTo develop and validate INCLEN Diagnostic Tool for Attention Deficit Hyperactivity Disorder (INDT-ADHD).DesignDiagnostic test evaluation by cross sectional design. Setting: Tertiary care pediatric centers.Participants156 children aged 65–117 months.MethodsAfter randomization, INDT-ADHD and Connor’s 3 Parent Rating Scale (C3PS) were administered, followed by an expert evaluation by DSM-IV-TR diagnostic criteria.Main outcome measuresPsychometric evaluation of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency.ResultsINDT-ADHD had 18 items that quantified symptoms and impairment. Attention deficit hyperactivity disorder was identified in 57, 87 and 116 children by expert evaluation, INDT-ADHD and C3PS, respectively. Psychometric parameters of INDT-ADHD for differentiating attention deficit hyperactivity disorder and normal children were: sensitivity 87.7%, specificity 97.2%, positive predictive value 98.0% and negative predictive value 83.3%, whereas for differentiating from other neuro-developmental disorders were 87.7%, 42.9%, 58.1% and 79.4%, respectively. Internal consistency was 0.91. INDT-ADHD has a 4-factor structure explaining 60.4% of the variance. Convergent validity with Conner’s Parents Rating Scale was moderate (r =0.73, P= 0.001).ConclusionsINDT-ADHD is suitable for diagnosing attention deficit hyperactivity disorder in Indian children between the ages of 6 to 9 years.

Incorporating developmental screening and surveillance of young children in office practice

ContextDevelopmental concerns voiced by parents need to be responded to by structured developmental screening. Screening is the use of validated developmental screening tools to identify children with high risk of developmental delay out of an apparently normal population, while surveillance is the process of monitoring children identified as high risk by screening. Absence of routine screening can be attributed to problems at the level of parents, pediatricians or National policies. Hence vulnerable children are not detected early, and are denied benefit from appropriate developmental interventions. There are no definite guidelines for screening or for suitable tools for screening and surveillance.ObjectivesTo review existing developmental screening and monitoring tools for children validated in Indian under-five children, and provide a proposed practice paradigm for developmental screening in office practice.Evidence AcquisitionScientific papers were retrieved by an electronic database search using MeSH terms ‘screening tool’, ‘developmental delay’, and filter of ‘children under 5 years’. Those relevant to office practice and validated internationally or in Indian children were reviewed.ResultsScreening tools applicable to Indian office practice have been compared and certain tools have been recommended according to the level of risk of developmental delay. An algorithmic approach to screening has been given along with strategies for incorporation.ConclusionsScreening and surveillance for high risk of developmental delay are essential components of child health care. It is possible to incorporate both into routine practice.

INCLEN Diagnostic Tool for Neuromotor Impairments (INDT-NMI) for primary care physician: development and validation.

ObjectivesTo develop and validate a diagnostic tool for use by primary care physicians for diagnosing neuro-motor impairment among 2–9 year old children in primary care settings.Study designModified Delphi technique involving national (n=49) and international (n=6) experts was used for development of INDT-NMI. The tool was then validated through a cross sectional study.SettingNeurology specialty clinics of three tertiary care pediatric centers in New Delhi, India.Participants454 children aged 2–9 years [mean (SD) age: 60.4 (23.7) mo], selected through systematic random sampling, underwent assessment for identification and classification of neuromotor impairments (NMI).InterventionAll study subjects were first administered INDT-NMI (candidate test) by a trained physician followed by expert assessment for NMI and other neurodevelopment disorders (NDD) by team of two pediatric neurologists (Gold standard).ResultsAccording to expert evaluation, 171 (37.8%) children had neuromotor impairments. There were four categories of subjects: NMI alone (n=66); NMI+other NDDs (n=105); Other NDDs without NMI (n=225) and ‘Normal’ group (n=58). Using expert evaluation as gold standard, overall sensitivity of the INDT-NMI was 75.4% and specificity was 86.8%. INDT-NMI helped graduate physicians to correctly classify 86.6% (112/129) children with NMI into different types (cerebral palsy, neuromotor diseases and other NMI). Graduate physicians assigned 40 children (8.8%) as ‘indeterminate’, 38 (95%) of whom had either NDD and/or NMI and thus merited referral. Misclassification of NMI occurred in those with mild changes in muscle tone, dystonia, or ataxia and associated NDDs.ConclusionGraduate primary care physicians with a structured short training can administer the new tool and diagnose NMI in 2–9 year old children with high validity. INDT-NMI requires further evaluation in actual primary care settings.

Efficacy and tolerability of the modified Atkins diet in young children with refractory epilepsy: Indian experience.

Background: The modified Atkins diet (MAD) has been used predominantly in older children, adolescents, and adults. There is a paucity of data on the use of the MAD in refractory epilepsy in young children. Objectives: This study was planned to evaluate the efficacy and tolerability of the MAD in refractory epilepsy in young children. Methods: This study recruited children aged 9 months to 3 years with refractory seizures. Children received MAD for 6-month with the on-going anticonvulsant medications being continued unchanged. Reduction in seizure frequency was the primary outcome measure. Adverse effects were also studied. Results: Thirty-one children with daily seizures were studied with a median age of 18-month (range 9-30 months). West syndrome was the most common epilepsy syndrome (26, 86.6%). Twenty-one children remained on diet at 3 months and 13 at 6 months. The children who achieved >50% seizure reduction were 17 (54.8%) at 3 months and 9 (29%) at 6 months. Refusal to eat was a significant problem seen in eight children. Three children discontinued the diet due to adverse effects. Conclusion: The MAD was found to be feasible, effective, and well-tolerated.

The Renal Cysts and Diabetes (RCAD) Syndrome in a Child with Deletion of the Hepatocyte Nuclear Factor-1β Gene

The authors describe a 14-yr-old boy who presented with non-ketotic hyperglycemia, elevated serum creatinine levels and deranged liver function. There was no microalbuminuria or proteinuria. He also had mild mental retardation with learning difficulties. Ultrasonography of the abdomen revealed multiple renal cysts of varying sizes in both the kidneys. Dosage analysis of the hepatocyte nuclear factor (HNF)-1β gene by multiplex ligation-dependent probe amplification (MLPA) detected a heterozygous whole gene deletion (p.Met1_Trp557del). This finding is consistent with the diagnosis of renal cysts and diabetes (RCAD) syndrome. This is the first case of the RCAD syndrome reported in an Indian patient. Pediatricians need to be aware of this entity whenever renal disease is seen in a diabetic child in the absence of microalbuminuria or proteinuria.

Sturge Weber–Like Gyral Calcification Seen in Tuberous Sclerosis Complex 1

A 10-year-old girl presented with poorly controlled epilepsy. On evaluation, she had microcephaly, neuro-cutaneous stigmata of tuberous sclerosis complex, profound mental retardation, and spastic hemiparesis. Computed tomography (CT) revealed a calcified subependymal nodule and extensive left gyral calcification of the temporal, parietal, and occipital regions with unilateral cerebral atrophy, radiologic features usually seen in Sturge Weber syndrome. Magnetic resonance imaging (MRI) revealed absence of tubers, enlarged choroid plexus, or leptomeningeal angiomas, thus excluding type 3 Sturge Weber syndrome. The genotype was a heterozygous mutation in exon 18 of the tuberous sclerosis type 1 gene (c.2293C>T p.Q765X). A comparison of previously reported 7 cases of Sturge Weber syndrome and tuberous sclerosis complex was made. This revealed 4 actual double phakomatoses (clinical, radiologic, or genetic phenotypes) and 3 cases with clinical phenotype of tuberous sclerosis and gyral calcifications within tubers simulating the radiologic picture of Sturge Weber syndrome.

Report of a novel Indian case of congenital erythropoietic porphyria and overview of therapeutic options.

Congenital erythropoietic porphyria is a rare disorder of heme biosynthesis, resulting from decreased enzymatic activity of uroporphyrinogen III synthase. Clinical manifestations are heterogenous, of variable severity, and with occasional phenotypic-genotypic correlation. A 14-month-old boy developed fever, extensive dermatitis, and reddish colored urine. Anemia, erythrodontia, hepatosplenomegaly, and massive urinary elimination of predominantly type I porphyrins was suggestive of congenital erythropoietic porphyria. Although hemolysis remained mild and compensated, facial and digital mutilation developed indicative of moderate clinical phenotype. Mutational analysis revealed compound heterozygosity of mutant alleles, including a novel mutation (p.Pro190Leu). The child received supportive management and underwent facial reconstruction successfully.

Hereditary Multiple Exostoses - A Tale of 50 years

We continue our expedition into the past while reviewing an article from the September 1965 issue data due to less severe forms associated with females or the gender bias in healthcare seeking behavior. In both of the cases, calcium, phosphorus and serum alkaline phosphatase levels in serum were normal. The only salient diagnostic findings were radiological (described later). Biopsies demonstrated proliferative chondroid tissue. The fungating mass in the second case was infectious, not malignant. The discussion of this article dwelt on various nomenclature, demographic characteristics, hereditary pattern (64% familial, remaining unknown or due to a new mutation), and clinical and radiological features (bony projections of various size and contour with the apex pointing towards the shaft and away from the nearest epiphysis, heterogeneously radio-opaque with interspersed areas of translucency). Historical background and past knowledge: A patient with multiple exostoses was presented in a lecture by Hunteras as early as 1786, while another with familial involvement was reported in 1814 [2,3]. Various terms based on the typical clinical and histopathological features (i.e. multiple osteochondromas, cartilaginous exostosis, deforming chondrodysplasia, diaphyseal aclasis) were in use. The prefix ‘hereditary’was added once the familial nature was recognized. HME remained an enigma till the 1950s when some groundbreaking research emerged. Solomon, et al. [4] delineated the clinical, radiological, pathological and genetic characteristics of HME in 1963. In this paper, it was stated that exostoses were cartilage-capped bony outgrowths from the juxta-ephipyseal regions of rapidly growing ends of bones originating in cartilage. Long bones and less commonly flat bones were described to be involved with sparing of face and skull. It was described that lesions appear by the end of the first decade, increase during puberty, and become dormant with cessation of growth. The number, size and location of exostoses were reported to vary between and within families. of Indian Pediatrics. This comprised of 41 pages with four research papers (ECG changes in progressive muscular dystrophy, a mathematical method to estimate gene frequencies, antenatal illnesses in villages of Punjab and a case series), two case records (pulmonary agenesis, polyarteritis nodosa), book reviews, current literature and news. We selected the case series of Hereditary multiple exostoses (HME), primarily to showcase the meticulousness with which the authors attempted to trace back the pedigree [1]. After briefly discussing the scientific knowledge that existed then, we will touch upon the recent advances that have evolved in understanding this disorder at the molecular and genetic levels.