Mutation of TBC1 Domain containing kinase (TBCK) with associated intellectual disability and hypotonia

Infantile Hypotonia with Psychomotor Retardation and Characteristic Facies-3 (IHPRF-3) Syndrome is a rare pathology occurring due to mutations in the TBC1 domain containing kinase (TBCK). This is a neurodevelopmental disorder presenting with a neurological and dysmorphic feature including intellectual disability, limb and craniofacial abnormalities. We present a case of TBCK mutation of the variant (p.Gln164*), present on Exon 6; this sequence change creates a premature translational stop signal (p.Gln164*) in TBCK, creating a disrupted protein leading to a loss of function. This variant has not yet been reported in genetic databases. We need to establish a better understanding of this disorder by reporting these novel genetic mutations so that these complex patients can be successfully managed by multidisciplinary teams. Keywords: Infantile hypotonia, Intellectual disability, Gene mutation

Potassium voltage-gated channel subfamily H member 1 (KCNH1) missense mutation causing epileptic encephalopathy and autistic behaviour

The phenotypically similar genetic diseases Zimmermann-Laband syndrome (ZLS) and Temple-Baraitser syndrome (TMBTS) cause neurodevelopmental problems. Mutations in the gene coding for potassium voltage-gated channel, primarily KCNH1, cause these symptoms. An uncommon mutation in KCNH1 (p.Arg357Trp) present on Exon 7, reported to replace arginine with tryptophan at codon 357 of the KCNH1 protein c.1069C>T, caused pharmacoresistant seizures and autistic behaviour in a 2.7-year-old boy. This mutation causes problems with protein modelling and has yet to be documented in any genetic databases around the world. This mutation was overlapped with GPHN gene, c.828+1G>A, in our patient, causing GPHN-related spectrum disorder (autosomal dominant) along with molybdenum cofactor deficiency (autosomal recessive) leading to a neuropsychiatric presentation including autistic behaviour, making diagnosis and management even more complicated. Keywords: Zimmermann-Laband syndrome, Temple-Baraitser syndrome, Autism, KCNH1 (p.Arg357Trp

Early infantile epileptic encephalopathy in asparagine-linked glycosylation thirteen (ALG13) gene defect and dramatic response with ketogenic diet

Asparagine-linked glycosylation thirteen (ALG13) gene-related congenital disorders of glycosylation (CDGs) include early onset epileptic encephalopathy (EIEE), developmental delays (DD) with intellectual disability (ID), speech and visual abnormalities, and haematologic and endocrine dysfunctions. Worldwide there is a scarcity of available data on this. To add to this scarce data, we report the case of a young girl with this rare genetic mutation who showed remarkable improvement in her seizures by addition of ketogenic diet (KD) to her management regimen. With an already high rate of consanguineous marriages, metabolic and genetic errors are widely prevalent; hence, to bridge the huge gap in the understanding of such diseases, further research and trials are needed to be carried out to improve identification of the disease along with outcomes

Early Infantile Epileptic Encephalopathy in asparagine-linked glycosylation thirteen (ALG13) gene defect and dramatic response with Ketogenic diet

Asparagine-linked glycosylation thirteen (ALG13) gene-related congenital disorders of glycosylation (CDGs) include early onset epileptic encephalopathy (EIEE), developmental delays (DD) with intellectual disability (ID), speech and visual abnormalities, and haematologic and endocrine dysfunctions. Worldwide there is a scarcity of available data on this. To add to this scarce data, we report the case of a young girl with this rare genetic mutation who showed remarkable improvement in her seizures by addition of ketogenic diet (KD) to her management regimen. With an already high rate of consanguineous marriages, metabolic and genetic errors are widely prevalent; hence, to bridge the huge gap in the understanding of such diseases, further research and trials are needed to be carried out to improve identification of the disease along with outcomes. Keywords: AGLT13 mutation, epileptic encephalopathy and ketogenic diet

Process evaluation of paediatric fellowship training programs at a university hospital in Pakistan

Background: Fellowship programs offer training in a subspecialty focusing on distinct and advanced clinical/academic skills. This advanced postgraduate training allows physicians, who desire a more specialized practice, to further develop clinical, academic, research, and leadership/administrative skills. The Aga Khan University (AKU) is one of the few institutes offering paediatric sub-specialty training in Pakistan. We aimed to evaluate the current Paediatric fellowship programs at AKU. Methods: Process evaluation of six paediatric fellowship programs (cardiology, neurology, endocrinology, critical care medicine, neonatology, and infectious disease) was conducted from September 2020 to April 2021 by senior clinicians and medical educationists. Evidence was collected through document review (using existing postgraduate medical education program information form), observation of teaching and learning support, and focused group discussions/interviews with program faculty and fellows were conducted. A review of the evaluation report was done as part of this study. This study received an exemption from the ethical review committee. The quantitative data were analyzed using SPSS (22.0) while the reports of discussion with fellows and friends underwent content analysis. Results: All fellowship programs met the criteria for having a robust competency-based fellowship curriculum as per the institutional and national guidelines. Formative assessment in the form of continuous evaluation was found to be integrated into all the fellowship programs, however, most of the programs were found to lack a summative assessment plan. Fellows in training and program faculty were satisfied with the opportunities for mentorship, teaching, and learning. Thematic analysis of the discussion reports with faculty and fellows revealed three key themes including, program aspects translating into strengthening the training, gaps in the training program in delivering the expectations, and making ways to reach par excellence. Conclusions: The process evaluation of paediatric fellowship programs provided an opportunity to holistically review the current strengths and quality of the training in individual programs along with the unmet needs of the trainees. This will help the program stakeholders to prioritize, align and allocate the resources to further enhance the quality of training and outcome of individual fellowship programs to ensure wider impacts at a regional, national, and international health system leve

Spectrum of common pediatric neurological disorders: A cross-sectional study from three tertiary care centres across Pakistan

Background: There is dearth of information on the spectrum of neurological disorders among children less than 18 years of age. The aim of this study is to identify the commonly presenting neurological disorders among children aged ≤ 18 years in Pakistan.Methods: We conducted a cross-sectional study at three tertiary care hospitals in Pakistan.Results: A total of 17,176 children were included in our study; 61.8% were boys and 38.2% females. The most commonly presenting neurological disorder was epilepsy (36%), followed by behavior disorders (16%) and cerebral palsy (10.5%). There was significant difference between children less than 5 years and greater than 5 years age groups, with less than 5 years age group showing higher prevalence for behavioral disorders (P \u3c 0.001), cerebral palsy (P \u3c 0.001), infections (P = 0.014), sequalae (P \u3c 0.001), and developmental disorders (P \u3c 0.001). Gender-wise distribution showed epilepsy to be the most common neurological disorder among both genders, with a significant difference being reported between gender and epilepsy (P = 0.009), headache disorders (P \u3c 0.001), neuroinflammatory disorders (P = 0.025), neurocutaneous syndromes (P \u3c 0.001), behavioral diseases (P \u3c 0.001), cerebral palsy (P = 0.009), and movement disorders (P \u3c 0.001).Conclusions: The result of this analysis helps to assess the commonly presenting neurological disorders in children. This study will help health care workers in resource-poor settings within Pakistan to be mindful of the common neurological disorders while diagnosing a child with neurological symptoms in an outpatient setting. Health care providers need to be trained to identify and treat these common conditions; however, there is still a dire need for more trained neurologists across the country