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Background Biotin–thiamine‐responsive basal ganglia disease (BTBGD) is an autosomal recessive neurometabolic disorder mostly presented in children. The disorder is described as having subacute encephalopathy with confusion, dystonia, and dysarthria triggered by febrile illness that leads to neuroregression and death if untreated. Using biotin and thiamine at an early stage of the disease can lead to significant improvement. Methods BTBGD is a treatable disease if diagnosed at an early age and has been frequently reported in Saudi population. Keeping this in mind, the current study screened 3000 Saudi newborns for the SLC19A3 gene mutations using target sequencing, aiming to determine the carrier frequency in Saudi Population and whether BTBGD is a good candidate to be included in the newborn‐screened disorders. Results Using targeted gene sequencing, DNA from 3000 newborns Saudi was screened for the SLC19A3 gene mutations using standard methods. Screening of the SLC19A3 gene revealed a previously reported heterozygous missense mutation (c.1264A>G (p.Thr422Ala) in six unrelated newborns. No probands having homozygous pathogenic mutations were found in the studied cohort. The variant has been frequently reported previously in homozygous state in Saudi population, making it a hot spot mutation. The current study showed that the carrier frequency of SLC19A3 gene mutation is 1 of 500 in Saudi newborns. Conclusion For the first time in the literature, we determined the carrier frequency of SLC19A3 gene mutation in Saudi population. The estimated prevalence is too rare in Saudi population (at least one in million); therefore, the data are not in favor of including such very rare disorders in newborn screening program at population level. However, a larger cohort is needed for a more accurate estimate.

Guillain-Barré syndrome (GBS) is a progressive acute form of paralysis most probably secondary to an immune-mediated process. GBS among Saudis has been seldom investigated, which leaves both clinicians and researchers with scarcity in knowledge. Therefore, this study aims to assess the prevalence and clinical prognosis of GBS among pediatrics admitted with acute paralysis at a large healthcare facility in Riyadh, Saudi Arabia. This retrospective study reviewed patients' medical records between 2005 and 2015. Eligible cases were children (<14 years old) admitted to the hospital complaining of acute paralysis and later diagnosed with one form or variant of GBS. Pearson's chi-square, Fisher's exact test, and binary logistic regression were employed to analyze the collected data. The prevalence of GBS was 49%. The male-to-female ratio was 1.45:1. The mean ± standard deviation age was 7±3.7 years. There were 34 (69.4%) cases with progression to maximum paralysis in ≤2 weeks, while 15 (30.6%) cases occurred beyond 2 weeks. Males (n=24, 82.8%) were more likely to endure progression to maximum paralysis in ≤2 weeks after the disease onset, compared to females (n=10, 50%), =0.014. All cases complaining of respiratory problems exhibited a progression to maximum paralysis in ≤2 weeks, compared to those with no respiratory problems, =0.027. Residual paralysis at 60 days post disease onset was highly associated with GBS patients of age 8-14 years (n=15, 65.2%), compared to younger patients (n=8, 30.8%), =0.016. Patients admitted in colder seasons (n=14, 63.6%) were more likely to suffer residual paralysis too, compared to those in warmer seasons (n=9, 33.3%), =0.035. GBS cases who complained of facial weakness (n=9, 75%) and ocular abnormalities (n=10, 71.4%) were also more likely to endure residual paralysis at 60 days post disease onset, =0.025 and =0.03, respectively. Male gender could be a determinant of rapid progression to maximum paralysis, while the older age group in pediatrics is expected to endure residual paralysis at 60 days post disease onset. GBS can be accounted as a rare disease, especially in pediatrics, so confirmed cases should be investigated comprehensively for research purposes.

BackgroundSelf-explanation while individually diagnosing clinical cases has proved to be an effective instructional approach for teaching clinical reasoning. The present study compared the effects on diagnostic performance of self-explanation in small groups with the more commonly used hypothetico-deductive approach.MethodsSecond-year students from a six-year medical school in Saudi Arabia (39 males; 49 females) worked in small groups on seven clinical vignettes (four criterion cases representing cardiovascular diseases and three ‘fillers’, i.e. cases of other unrelated diagnoses). The students followed different approaches to work on each case depending on the experimental condition to which they had been randomly assigned. Under the self-explanation condition, students provided a diagnosis and a suitable pathophysiological explanation for the clinical findings whereas in the hypothetico-deduction condition students hypothesized about plausible diagnoses for signs and symptoms that were presented sequentially. One week later, all students diagnosed eight vignettes, four of which represented cardiovascular diseases. A mean diagnostic accuracy score (range: 0–1) was computed for the criterion cases. One-way ANOVA with experimental condition as between-subjects factor was performed on the mean diagnostic accuracy scores.ResultsStudents in the hypothetico-deduction condition outperformed those in the self-explanation condition (mean = 0.22, standard deviation = 0.14, mean = 0.17; standard deviation = 0.12; F(1, 88) = 4.90, p = 0.03, partial η2 = 0.06, respectively).ConclusionsStudents in the hypothetico-deduction condition performed slightly better on a follow-up test involving similar cases, possibly because they were allowed to formulate more than one hypothesis per case during the learning phase.

Background King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) was the first university in the Kingdom of Saudi Arabia offering both high school entry and graduate entry (GE) students into medical school. We compared the academic performance and professionalism lapses of high school entry and GE students who undertook the same curriculum and examinations in the College of Medicine, Riyadh, KSAU-HS. Methods Examination scores of 196 high school graduates and 54 GE students over a 4-year period (2010–2014) were used as a measure of academic achievement. For assessment of professionalism lapses, we compared the number of warning letters in both streams of students. Results In some pre-clinical courses, high school entry students performed significantly better than GE students. There was no significant difference in academic performance of high school entry and GE students in clinical rotations. GE students had a significantly greater number of warning letters per student as compared to high school entry students. Discussion This is the first Saudi study to compare the performance of high school entry and GE students in a medical school. Overall, both streams of students performed equally well with high school entry students performing better than GE students in a few pre-clinical courses. We compared professionalism lapses and found an increase in number of warning letters for GE students. More studies are needed to evaluate if there are differences in other assessments of professionalism between these two streams of students.

Von Willebrand A domain-containing protein 8 ( VWA8 ), also named KIAA0564, is a poorly characterized, mitochondrial matrix-targeted protein having a putative ATPase activity. VWA8 is comprising of ATPase-associated domains and a VWFA domain associated with ATPase activity inside the cell. In the present study, we describe a large consanguineous family of Saudi origin segregating a complex developmental syndrome in an autosomal recessive fashion. All the affected individuals exhibited severe developmental disorders. DNA from three patients was subjected to whole-exome sequencing followed by Sanger sequencing. VWA8 knock-down zebrafish morpholinos were used to study the phenotypic effect of this gene on zebrafish development. A homozygous missense variant [c.947A > G; p.(Asp316Gly)] was identified in exon 8 of the VWA8 gene, which perfectly segregated with the disease phenotype. Using zebrafish morpholino, we observed delayed development at an early stage, lack of movement, light sensitivity, severe skeletal deformity such as scoliosis, and facial dysmorphism. This is the first homozygous variant identified in the VWA8 gene underlying global developmental delay, microcephaly, scoliosis, limbs, and cardiovascular malformations in humans. We provide genetic and molecular evidence using zebrafish morpholino for a homozygous variant in the VWA8 gene, associated with such a complex developmental syndrome in humans.

Duchenne muscular dystrophy (DMD) is a severe and rare X-linked neuromuscular childhood disorder that results in functional decline, loss of ambulation and early death due to cardiac or respiratory failure. The objective of this paper is to address different aspects of the current management of DMD in the Middle East, north Africa (MENA) region, and to gather experts’ recommendations on how to optimally diagnose and treat patients suffering from this disease. A group of experts (neuromuscular medicine, neuropediatricians and geneticists) convened to discuss the diagnosis and management of DMD in the MENA region. A list of practical statements was prepared by the chair of the meeting to guide the discussions around critical aspects relating to the current and future management of DMD. Ideally, DMD management should be a multidisciplinary approach. Nevertheless, few tertiary care hospitals in the region are currently able to provide the full spectrum of medical expertise and services needed by DMD patients. Clinical practice in the region remains heterogeneous. Specific guidelines for diagnosis and treatment are needed in the MENA region to improve outcomes. Disease awareness among the general public and the medical community is lacking. Now that mutation-specific therapies are being developed and more widely studied, general education programs regarding early signs and symptoms, a standardized referral and diagnosis pathway, patient registries and support groups will significantly improve the management of the disease.

Joubert syndrome is a congenital brain malformation of the cerebellar vermis and brainstem with abnormalities of axonal decussation (crossing in the brain) affecting the corticospinal tract and superior cerebellar peduncles 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 . Individuals with Joubert syndrome have motor and behavioral abnormalities, including an inability to walk due to severe clumsiness and 'mirror' movements, and cognitive and behavioral disturbances 5 , 6 , 7 , 8 , 10 , 11 , 12 . Here we identified a locus associated with Joubert syndrome, JBTS3, on chromosome 6q23.2–q23.3 and found three deleterious mutations in AHI1 , the first gene to be associated with Joubert syndrome. AHI1 is most highly expressed in brain, particularly in neurons that give rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles. Comparative genetic analysis of AHI1 indicates that it has undergone positive evolutionary selection along the human lineage. Therefore, changes in AHI1 may have been important in the evolution of human-specific motor behaviors.

We report our results of 1000 diagnostic WES cases based on 2819 sequenced samples from 54 countries with a wide phenotypic spectrum. Clinical information given by the requesting physicians was translated to HPO terms. WES processes were performed according to standardized settings. We identified the underlying pathogenic or likely pathogenic variants in 307 families (30.7%). In further 253 families (25.3%) a variant of unknown significance, possibly explaining the clinical symptoms of the index patient was identified. WES enabled timely diagnosing of genetic diseases, validation of causality of specific genetic disorders of PTPN23, KCTD3, SCN3A, PPOX, FRMPD4, and SCN1B, and setting dual diagnoses by detecting two causative variants in distinct genes in the same patient. We observed a better diagnostic yield in consanguineous families, in severe and in syndromic phenotypes. Our results suggest that WES has a better yield in patients that present with several symptoms, rather than an isolated abnormality. We also validate the clinical benefit of WES as an effective diagnostic tool, particularly in nonspecific or heterogeneous phenotypes. We recommend WES as a first-line diagnostic in all cases without a clear differential diagnosis, to facilitate personal medical care.

Introduction: Adrenocorticotropic hormone (ACTH) is a tropic hormone naturally secreted by the anterior pituitary gland to stimulate the secretion of cortisol and androgens. ACTH is used in non-tuberous sclerosis infantile epileptic spasms syndrome (IESS), and it has shown significant, promising results in epilepsy syndromes with possible inflammatory processes. However, many studies have also demonstrated a promising potential even in other types of drug-resistant epilepsy. Material and method: This study is a retrospective observational study that follows the clinical characteristics and outcomes of nine pediatric patients with drug-resistant epilepsy treated with short-term synthetic ACTH in Saudi Arabia. The response was assessed during the ACTH infusion and after three months.Results: During infusion, six of the nine (66%) patients had a short-term (within two weeks) favorable response, with a more than 50% reduction in seizure frequency. Four of the nine (44%) patients had complete responses with seizure freedom. After three months, four patients (44%) had a three-month seizure frequency reduction of more than 30% attributed to ACTH, including one patient with an IESS history who had a 70% reduction in seizure frequency. Of the four patients who had a complete response, three (75%) had a seizure relapse after tapering in the following three months. Conclusion: This case series adds to the literature to suggest ACTH treatment of drug-resistant epilepsies other than IESS might benefit some patients in the acute setting but they are less likely to maintain a sustained treatment response. Randomized and large sample size studies are necessary to assess treatment response and accurately aid in appropriate patient selection.