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The two genetically similar severe acute respiratory syndrome coronaviruses, SARS-CoV-1 and SARS-CoV-2, have each been responsible for global epidemics of vastly different scales. Although both viruses arose from similar origins, they quickly diverged due to differences in their transmission dynamics and spectrum of clinical presentations. The potential involvement of multiple organs systems, including the respiratory, cardiac, gastrointestinal and neurological, during infection necessitates a comprehensive understanding of the clinical pathogenesis of each virus. The management of COVID-19, initially modelled after SARS and other respiratory illnesses, has continued to evolve as we accumulate more knowledge and experience during the pandemic, as well as develop new therapeutics and vaccines. The impact of these two coronaviruses has been profound for our health care and public health systems, and we hope that the lessons learned will not only bring the current pandemic under control, but also prevent and reduce the impact of future pandemics.

Introduction: Mutations in genes-encoding collagen VI-a chain are known to cause congenital muscular dystrophies, (CMDs). Aim: Screening for COL6A mutations in CMDs’ patients. Methods: WGS, Sanger sequencing, plasmids-construction, Western-blot and RT-PCR. Results: Missense and novel nonsense mutations in COL6A1 and COL6A2 were detected. The analysis revealed a decreased stability of the COL6A mutants as compared to wild-type. Conclusion: Collagen related muscular dystrophies may demonstrate the early presentation as of joints and bone involvement rather than of muscular weakness hence, likely may be misdiagnosed. Collagen VI muscular dystrophy was not identified in Qatari patients with muscular dystrophies, in our cohort.

Although muscular diseases are monogenetic disorders, inherited in an autosomal recessive (AR), dominant or X-linked pattern, the marked variability in genetics and presentations can be identified within the same category of a subtype and among patients even with the same gene involvement. Gulf and Arab populations are characterized by a high rate of consanguineous marriages, which favors the appearance of such group of muscular and neuromuscular diseases in multiple and successive generations. In this presentation, we will discuss the spectrum of genetic muscular diseases in Qatar and identify the particular genetic causes of muscular disorders in our population.The presentation learning objectives involve:1- Epidemiology of muscular diseases in Qatar2- Clinical presentation of muscular diseases in Qatar3- Managements and outcomes

Neuromuscular disorders (NMDs) present a large group of primary muscle weakness’ diseases that progressively affect the subjects’ walking and movements’ abilities. Associated extra-muscular involvements constitute chronic co-morbidities that disturb the patients’ quality of life. There are challenges to better serve NMDs’ chronic patients that require a multidisciplinary team of health care providers. Hence, it is of importance to discuss what approaches are taken to ensure high quality integrated-health measures that aim at advancing the standard care and management plans for these patients in Qatar. The tertiary prevention approach of carrier and prenatal detection or the primary prevention applying the preimplantation genetic diagnosis has a principal role in reducing the recurrence of NMDs in our families and community. Hence, the question up for discussion is whether our prevention genetic program serves the needs for such families. Newborn screening is implemented in Qatar for a pre-designed list of diseases. The panel discussion will address the potential need for a tailored screening program for treatable types of congenital dystrophies or myopathies. Moreover, patients’ voices are known to have a powerful influence on the heath authorities’ decision-making. Patient advocacy groups are groups dedicated to taking patient’s voices to the forefront, these groups are well acting worldwide, and so are we ready to start this experience here in Qatar?

We report a consanguineous Arab family with three affected siblings who display a disorder of global developmental delay, learning difficulties, facial dysmorphism, hearing impairments, and cataract. The clinical phenotype was associated with characteristic brain Magnetic Resonance Imaging (MRI) features of axonal guidance defects involving anterior commissure agenesis as well as scattered areas of polymicrogyria-cobblestone complex. Whole genome sequencing revealed a novel nonsense mutation (159609921C>T) that segregated in the family consistent in an autosomal recessive pattern. This mutation located in the C-terminal region shared by the Schwanomin-Interacting Protein1 (SCHIP1) isoforms including the IQCJ-SCHIP1. The in-vitro expression of SCHIP1 and IQCJ-SCHIP1 truncated mutant isoforms (NM_001197109.1; p.R209* and NM_001197114.1; p.R501*, respectively) were markedly reduced as compared to their full-length versions suggesting protein stability/folding impairment. The pathogenic nature of this mutation is supported by a previously reported mouse knockout of Schip1 isoforms, which phenocopied the human axon guidance abnormality. This is the first report of a SCHIP1/IQCJ-SCHIP1 point mutation in humans associated with a neurological-developmental phenotype.

Arthrogryposis multiplex congenital, the occurrence of multiple joint contractures at birth, can in some cases be accompanied by insufficient myelination of peripheral nerves, muscular hypotonia, reduced tendon reflexes, and respiratory insufficiency. Recently mutations in the CASPR/CNTN1 complex have been associated with similar severe phenotypes and CNTNAP1 gene mutations, causing loss of the CASPR protein, were shown to cause severe, prenatal onset arthrogryposis multiplex congenita in four unrelated families. Here we report a consanguineous Arab family from Qatar with three children having an early lethal form of arthrogryposis multiplex congenita and a novel frameshift mutation in CNTNAP1. We further expand the existing CNTNAP1-associated phenotype to include profound cerebral and cerebellar atrophy.

Objective Exome sequences account for only 2% of the genome and may overlook mutations causing disease. To obtain a more complete view, whole genome sequencing (WGS) was analyzed in a large consanguineous family in which members displayed autosomal recessively inherited cerebellar ataxia manifesting before 2 years of age. Methods WGS from blood-derived genomic DNA was used for homozygosity mapping and a rare variant search. RNA from isolated blood leukocytes was used for quantitative polymerase chain reaction (PCR), RNA sequencing, and comparison of the transcriptomes of affected and unaffected family members. Results WGS revealed a point mutation in noncoding RNA RNU12 that was associated with early onset cerebellar ataxia. The U12-dependent minor spliceosome edits 879 known transcripts. Reverse transcriptase PCR demonstrated minor intron retention in all of 9 randomly selected RNAs from this group, and RNAseq showed splicing disruption specific to all U12-type introns detected in blood monocytes from affected individuals. Moreover, 144 minor intron–containing RNAs were differentially expressed, including transcripts for 3 genes previously associated with cerebellar neurodegeneration. Interpretation Interference with particular spliceosome components, including small nuclear RNAs, cause reproducible uniquely distributed phenotypic and transcript-specific effects, making this an important category of disease-associated mutation. Our approach to differential expression analysis of minor intron–containing genes is applicable to other diseases involving altered transcriptome processing. ANN NEUROL 2017;81:68–78

Congenital LAMA2 related muscular dystrophy (LAMA2-RD), the most commonly recognized type of congenital muscular dystrophies, has been described in patients' cohorts from Europe and the UK but not from Middle-Eastern. This study aimed to reveal the prevalence, clinical and genomic characteristics of congenital LAMA2-RD in a patient's cohort of 17 families (21 patients) from the Gulf and Middle East. Affected subjects exhibited the classic phenotype of generalized hypotonia, developmental delay, and progressive muscular weakness. Despite the homogeneous background of most of our patients, clinical variability was evident; however, none of our patients was able to achieve independent ambulation. The associated features of nephrocalcinosis, infantile-onset osteopenia, and cardiac arrest were first described in this study. LAMA2 mutations constituted 48% of the genetic causes underlying congenital muscular dystrophies (CMDs) in our patients. We estimated a point prevalence of 0.8 in 100.000 for LAMA2-RD in Qatar, relatively higher compared to that described in Europe's studies. The founder mutation and high rate of consanguinity are potential contributors. This study identified five LAMA2 truncating variants, two novel and three recurrent, of which the c.6488delA-frameshift that was found in 12 unrelated Qatari families, highlighting a founder mutation in Qatari patients. The two novel variants involved an acceptor splice site and N-terminus deletion that removes the LAMA2 promoter, exon1, and part of intron1. The "residual" expression of LAMA2 transcript and protein associated with this large N-terminus deletion suggested an alternative promoter that, while seems to be activated, acts less efficiently.

Introduction: Ataxia telangiectasia (AT) is a rare disease characterized by immunodeficiency and neurological manifestations. Ataxia, resulting from cerebella atrophy, runs a progressive incapacitating course. Clinical monitoring of the disease course is mandatory for early treatment. Aim: To study clinical severity of AT and correlate it with the degree of cerebellar atrophy. Patients and Methods: We retrospectively studied all children (less than 14 years) with AT seen at Hamad General Hospital Clinics between 1998-2013. We collected basic demographic data, parental consan-guinity, family history, AT clinical severity scores, and reviewed CBC with differential counts; alpha-fetoprotein, serum immunoglobulins and lymphocyte subsets. Cranial MRI scans of each subject were reviewed by a neuroradiologist. Cerebellar atrophy was visually and semi-quantitatively scored. Results: We analyzed data on 18 AT children (10 males and 8 females), mean age of 76.9 months. 77.8% had a positive family history of AT and 41.7% parental consanguinity. Lymphopenia was observed in 77.8% and high serum alpha-fetoprotein in 87.5% of children. Clinical severity of ataxia was 17.1 ± 8.4 (mean ± SD); 86.7% of patients were moderate-severe. MRI cerebellar atrophy score was 1.9 ± 1.3 (mean ± SD), and moderate in 51% of patients. AT clinical severity score correlated (coefficient r = 0.566) but not statistically significant p = 0.088) with MRI cerebellar atrophy scores. Conclusions: Moderate to severe ataxia and marked cerebellar atrophy are quite common in AT children. There is a correlation between AT clinical severity and cerebellar atrophy. Larger prospective studies might further determine the significance of our observations and help practicing practitioners monitor the progression of the disease.

Objective The objective of this study was to investigate the genetic etiology of the X-linked disorder “Hypomyelination of Early Myelinating Structures” (HEMS). Methods We included 16 patients from 10 families diagnosed with HEMS by brain MRI criteria. Exome sequencing was used to search for causal mutations. In silico analysis of effects of the mutations on splicing and RNA folding was performed. In vitro gene splicing was examined in RNA from patients’ fibroblasts and an immortalized immature oligodendrocyte cell line after transfection with mutant minigene splicing constructs. Results All patients had unusual hemizygous mutations of PLP1 located in exon 3B (one deletion, one missense and two silent), which is spliced out in isoform DM20, or in intron 3 (five mutations). The deletion led to truncation of PLP1, but not DM20. Four mutations were predicted to affect PLP1/DM20 alternative splicing by creating exonic splicing silencer motifs or new splice donor sites or by affecting the local RNA structure of the PLP1 splice donor site. Four deep intronic mutations were predicted to destabilize a long-distance interaction structure in the secondary PLP1 RNA fragment involved in regulating PLP1/DM20 alternative splicing. Splicing studies in fibroblasts and transfected cells confirmed a decreased PLP1/DM20 ratio. Interpretation Brain structures that normally myelinate early are poorly myelinated in HEMS, while they are the best myelinated structures in Pelizaeus–Merzbacher disease, also caused by PLP1 alterations. Our data extend the phenotypic spectrum of PLP1-related disorders indicating that normal PLP1/DM20 alternative splicing is essential for early myelination and support the need to include intron 3 in diagnostic sequencing.

Background Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative diseases. Thin Corpus Callosum (TCC) associated HSP is a distinguished subgroup of complex forms. Purines and pyrimidine, the basic DNA and RNA components, are regulating the cell metabolism, having roles in signal transduction, energy preservation and cellular repair. Genetic defects in nucleotide metabolism related genes have been only recently implicated in brain and neurodegenerative diseases’ pathogenesis. Case presentation We present a consanguineous Qatari family with two brothers, 9 and 3 years, who displayed a characteristic phenotype of early onset and markedly-severe spasticity with tiptoe walking, delayed dysarthric speech, persistent truncal hypotonia, and multiple variable-sized areas of brownish skin discoloration appearing at different places on the body. A clinical diagnosis suggestive of complex hereditary spastic paraplegia (HSP) was set after the family had the second affected child. Whole genome sequencing identified a novel homozygous NT5C2 splice site mutation (NM_012229.4/NM_001134373.2: c.1159 + 1G > T) that recessively segregated in family members. Brain MRI revealed dysgenic and thin corpus callosum (TCC) with peri-trigonal white matter cystic changes in both affected boys, whereas a well-developed corpus callosum with normal white matter was shown in their apparently normal brother, who found to be a carrier for the mutant variant. This mutation led to skipping of exon 14 with removal of 58 amino acid residues at the C-terminal half. The aberrantly spliced NT5C2 showed substantial reduction in expression level in the in-vitro study, indicating marked instability of the mutant NT5C2 protein. Conclusion The present report expands the phenotypic spectrum of SPG45 and confirms NT5C2-SPG45 as a member of the rare TCC SPG-subtypes. Homozygous alteration in NT5C2 seems essential to produce central white matter developmental defects. The study highlights the importance of cytosolic II 5’-nucleotidase (NT5C2) in maintaining the normal balance of purines’ pool in the brain, which seems to play a pivotal role in the normal development of central white matter structures. Electronic supplementary material The online version of this article (doi:10.1186/s12881-017-0395-6) contains supplementary material, which is available to authorized users.

Background WW domain containing oxidoreductase (WWOX) gene was cloned in 2000; alteration has been seen in many cancer cells. It acts as a tumor suppresser by blocking cell growth and causing apoptosis. WWOX protein showed different expression of mice brain and spinal cord, for which deletion causes seizure and early death. Case presentation Clinical and molecular characteristics of a consanguineous family show a homozygous mutation of WWOX gene at specific bases, causing a debilitating syndrome characterized by growth retardation, intractable epilepsy, intellectual disability, and early death. Using Whole Exome Sequencing (WES), a novel homozygous mutation in the WWOX gene is identified in a consanguineous Arab family from Qatar with two daughters who presented with intractable seizure and developmental delay. Conclusion The study presents the importance of human WWOX gene for brain development and the association between gene mutation and epileptic encephalopathy. It also highlights the power of WES particularly in clinically challenging cases.

We report on a mother and two children from a consanguineous Arab Qatari family demonstrating a highly distinctive pattern of intracranial calcification involving the globus pallidus, posterior limb of the internal capsule, genu of the corpus callosum, and deep white matter. Both siblings, a girl and boy, presented with neonatal seizures without subsequent deterioration in neurological function. The girl demonstrated mild to moderate psychomotor delay but her brother and mother showed completely normal development. All three affected individuals were normocephalic. To the best of our knowledge this phenotype represents a novel disorder of inherited brain calcification, which may be recognizable on computerized tomography brain imaging in other cases. Although the disease shows apparent autosomal dominant inheritance, the high degree of consanguinity in the family leaves open the possibility of pseudo-dominance for an autosomal recessive trait.

Item does not contain fulltext GLUT1 deficiency syndrome (GLUT1DS) is understood as a monogenetic disease caused by heterozygous SLC2A1 gene mutations with autosomaldominant and sporadic transmission. We report on a six-year-old girl from an inbred Arab family with moderate global developmental delay, epilepsy, ataxia, hypotonia, and hypoglycorrhachia (CSF glucose 36 mg/dL; CSF lactate 1.09 mmol/L; CSF/blood glucose ratio 0.44). Molecular analysis of the SLC2A1 gene identified a novel homozygous c1402C>T (p. Arg468Trp) mutation in exon 10 in the index patient and her asymptomatic younger sister. The mutation was absent in 120 control alleles of healthy individuals as well as in 400 alleles of other GLUT1DS patients. Arg468 represents a highly conserved, functionally important amino acid residue in the GLUT1 carboxy-terminus essential for substrate recognition and transport. Both unaffected parents were heterozygous for the mutation. A younger brother and two family members were healthy and carried the GLUT1 wild type. A ketogenic diet effectively controlled seizures in the index patient. We conclude that GLUT1DS can be transmitted as an autosomal recessive disease and provide new insights into genetic counselling for this treatable disorder. 01 oktober 2009

Objectives/design Comparative cross-sectional study to assess homocysteine and vitamin status in carriers of CBS gene mutations. Method Subjects included 34 parents (13 males, 21 females, age 27–59 years) of 30 patients with classical homocystinuria due to homozygous cystathionine β-synthase deficiency. Control subjects were matched for gender and age (13 males, 21 females, age 25–59 years). All subjects were of Qatari origin, had normal liver and renal function tests and had not taken drugs or vitamin supplements prior to the study. The concentrations of homocysteine, folic acid and vitamins B 6 and B 12 in blood were determined after an overnight fast. Results Heterozygous carriers had significantly increased fasting levels of homocysteine compared to controls (9.1 vs. 8.1μmol/l, P =0.012). Both folic acid (328 vs. 478pmol/l, P =0.002) and vitamin B 12 concentrations (232 vs. 287pmol/l, P =0.013) were reduced whilst there was no significant difference in vitamin B 6 levels between the two groups (5.8 vs. 6.44μg/l). Conclusions Increased homocysteine concentrations in CBS gene mutation carriers are associated with reduced concentrations of folic acid and vitamin B 12 in blood. In view of the adverse effects of mild hyperhomocysteinemia, routine testing of vitamin status in parents of homocystinuria patients may be warranted. The causal relationship and pathophysiological consequences are uncertain; it is likely that CBS gene mutation carriers need higher doses of dietary vitamins.

We present a Qatari family with two children who displayed a characteristic phenotype of congenital marked pain insensitivity with hypohidrosis and progressive aseptic destruction of joints and vertebrae resembling that of hereditary sensory and autonomic neuropathies (HSANs). The patients, aged 10 and 14, remained of uncertain genetic diagnosis until whole genome sequencing was pursued. Genome sequencing identified a novel homozygous C65S mutation in the LIFR gene that is predicted to markedly destabilize and alter the structure of a particular domain and consequently to affect the functionality of the whole multi-domain LIFR protein. The C65S mutant LIFR showed altered glycosylation and an elevated expression level that might be attributed to a slow turnover of the mutant form. LIFR mutations have been reported in Stuve-Wiedemann syndrome (SWS), a severe autosomal recessive skeletal dysplasia often resulting in early death. Our patients share some clinical features of rare cases of SWS long-term survivors; however, they also phenocopy HSAN due to the marked pain insensitivity phenotype and progressive bone destruction. Screening for LIFR mutations might be warranted in genetically unresolved HSAN phenotypes.

Background: Hurst disease is the rarest yet the most fatal form of acute demyelinating encephalomyelitis. There around 100 cases around the world, 10 of them are pediatric patients. The disease is quite severe in course and aggressive therapy is crucial to help improving the outcome. We are reporting a rather successful story of early recognition and treatment of young toddler with using all lines of known therapies simultaneously and aggressively. Case report: We are reporting 2 ½ years old girl who was previously healthy. She has some viral prodromal illness ended by severe encephalopathy. She has found to have novel H1N1 infection. Early plasma exchange and therapeutic hypothermia have been simultaneously utilized. There was obvious significant fast improvement in clinical status thereafter. Discussion: Immune therapy is advised in treating Hurst disease. One trial of hypothermia has been suggested in one case report. However, Combination of early use of plasma exchange and therapeutic hypothermia has not been reported in literature up to our knowledge. Our patient showed impressive clinical progress following these rarely used procedures. Conclusion: Recognition of autoimmune encephalitis especially the most severe forms is a must. If the patient shows enough clinical and radiological signs suggestive of Hurst disease, then aggressive immunotherapy and therapeutic hypothermia should be considered. A more favorable outcome might be reached using these therapies simultaneously

Oculo-ectodermal syndrome (OES - OMIM 600628), also known as Toriello Lacassie Droste syndrome, is a very rare condition, first described by Toriello et al., in 1993. OES has been proposed to be a mild variant of encephalocraniocutaneous lipomatosis (ECCL). It is characterized by aplasia cutis congenita (ACC), epibulbar dermoids, coarctation of the aorta, arachnoid cysts in the brain, seizure disorder, hyperpigmented nevi, non-ossifying fibromas and a predisposition to develop giant cell tumors of the jaw. There are few reported cases of OES worldwide but with no definite diagnostic criteria yet. We present a case in a child with unilateral hyperpigmented nevi and ACC on the scalp, ocular lesions (lipodermoid cysts and coloboma), temporal arachnoid cyst, spinal lipomatosis and aortic coarctation with the aim of enhancing the foundation to establish diagnostic criteria for this condition. It additionally serves as a teaching point to emphasize the importance of pursuing a definite diagnosis when faced with such a multisystem illness, to counsel patients and their parents regarding long term morbidity and overall prognosis.

Background With diminishing costs of next generation sequencing (NGS), whole genome analysis becomes a standard tool for identifying genetic causes of inherited diseases. Commercial NGS service providers in general not only provide raw genomic reads, but further deliver SNP calls to their clients. However, the question for the user arises whether to use the SNP data as is, or process the raw sequencing data further through more sophisticated SNP calling pipelines with more advanced algorithms. Results Here we report a detailed comparison of SNPs called using the popular GATK multiple-sample calling protocol to SNPs delivered as part of a 40x whole genome sequencing project by Illumina Inc of 171 human genomes of Arab descent (108 unrelated Qatari genomes, 19 trios, and 2 families with rare diseases) and compare them to variants provided by the Illumina CASAVA pipeline. GATK multi-sample calling identifies more variants than the CASAVA pipeline. The additional variants from GATK are robust for Mendelian consistencies but weak in terms of statistical parameters such as TsTv ratio. However, these additional variants do not make a difference in detecting the causative variants in the studied phenotype. Conclusion Both pipelines, GATK multi-sample calling and Illumina CASAVA single sample calling, have highly similar performance in SNP calling at the level of putatively causative variants. Electronic supplementary material The online version of this article (doi:10.1186/1756-0500-7-747) contains supplementary material, which is available to authorized users.

Combined clinical, neuroimaging, genomics, and molecular genetics research efforts between neuropediatrics clinic at HMC, international clinical collaborators, and neurogentics lab at WCMCQ has successfully enabled a prominent achievement in providing tools and defined strategy for diagnostics, and primary prevention, carrier detection and prenatal intervention, of a wide variety of neurogenetics diseases encountered in Gulf and Arab patients. Whole genome sequencing, Sanger sequencing, in-vitro studies were our main experimental tools to prove the gene defect and to derive the well characterized diagnostic tool. Examples of diseases that are identified in our collection of families and now possible to screen and diagnose on gene basis include AR-Leukodystroph y with subcortical cysts [ VDK], ARLGMD-sarcoglycan s, AR-HSP-related genes, AR-hyperexplexia and other interesting neurogentics disorders. The presentation will show a summary of clinical, neuroimaging, novel genes/ mutations and the preventive measures that have been actually undertaken in those diseases. Health and Biomedical

Objective To determine whether abnormal EEG and neuroimaging are to be considered as valuable predictors for intractable epilepsy and to identify such electroencephalographic and radiological abnormalities associated with medical intractability in children with epilepsy. Methods All children who had a diagnosis of epilepsy in Hamad general hospital before age 5 years from January 2012 till December 2013 were studied; their EEG and neuroimaging results were evaluated and assessed in regard to their long-term epilepsy control. Results Around 90% of children fulfilling diagnosis of intractable epilepsy were below 3 years of age. Male to female ratio was 2:3. 67% of patients cohort had initial abnormal neuro-imaging. More than 70% had abnormal EEG at begining of their illness. Conclusion Early observation and looking for the risk factors for intractable epilepsy may decrease the cost for health care utilization. Medical intractability in childhood epilepsy can be predicted by monitoring these factors, among these factors are: Diagnosis before age 12 months, Abnormal neuroimaging including congenital brain anomalies and acquired insult fallowing asphyxia and traumatic brain injury, and abnormal initial EEG including multifocal spike and wave and abnormal background

To study the changes in the epidemiology of bacterial meningitis in the era of the Hemophilus influenzae (H. influenzae) type b vaccine and pneumoccous resistance.Retrospective study which included patients admitted to Hamad Medical Corporation, Doha, Qatar between January 1998 through to December 2000 with positive cerebrospinal fluid culture.Thirty-seven patients with culture proven bacterial meningitis were described. Streptococcus pneumoniae (S. pneumoniae) and H. influenzae were the most common organisms, accounting for 30% and 24% of cases. Fever, neck stiffness, vomiting, and bulging fontanel were the most frequent presenting features. Fifty four percent of S. pneumoniae isolates were resistant to penicillin, and 22% of H. influenzae were resistant to ampicillin, but both were sensitive to ceftriaxone. No cases of Listeria monocytogenes meningitis were diagnosed. Morbidity was 32%, and mortality 5%. Poor outcome was associated with altered mental status on admission.Bacterial meningitis is a serious illness in our community with significant morbidity and mortality. Streptococcus pneumoniae and H. influenzae are the most frequent pathogens causing meningitis in our community. As there is no bacterial resistance (S. pneumoniae and H. influenzae) reported against ceftrixone, we recommend ceftriaxone alone as empiric therapy for patients with no comorbid conditions presenting with community acquired bacterial meningitis. A continuous surveillance for changes in the microbiology of organisms causing bacterial meningitis or their sensitivity in our community is essential to update these recommendations.

Objective: To describe 4 children with a novel hypomyelinating leukoencephalopathy, defined by a distinct pattern of magnetic resonance imaging (MRI) abnormalities. Design: In our ongoing study on leukoencephalopathies of unknown origin, MRIs of patients are rated in a standardized manner. Patients are grouped according to their MRI abnormalities. The clinical and laboratory data are retrospectively reviewed. Subjects: The MRIs of approximately 3000 patients with a leukoencephalopathy of unknown origin were initially evaluated. Four unrelated patients (all male, aged 1.8-7.4 years) displayed similar MRI alterations. Results: Patients displayed mild T2 hyperintensity of the medulla oblongata, caudal part of the pons, hilus of the dentate nucleus, peridentate white matter, subcortical cerebellar white matter, optic radiation, and frontoparietal periventricular white matter. The posterior limb of the internal capsule showed alternating T2 hyperintensehypointense-hyperintense stripes in 3 patients. The T1-weighted images showed hyperintensity, isointensity, or mild hypointensity of T2 hyperintense structures. The thalamus had a neonatal appearance with a mildly hyperintense signal except for a darker lateral part. Clinically, patients presented with nystagmus between ages 6 and 20 months. Over time, cerebellar ataxia and mild spasticity developed. All achieved unsupported walking. Cognition and language were normal. Known causes of hypomyelination were excluded. Conclusions: The patients share a striking pattern of MRI abnormalities and have a similar clinical picture, suggesting that they have the same disorder. The hypomyelination in this disorder specifically occurs in structures that normally myelinate early. We hypothesize that the disease is caused by a defect in a gene involved in early myelination. ©2012 American Medical Association. All rights reserved.

This study sought to genetically define the first family diagnosed with neuronal ceroid lipofuscinosis from Qatar. Onset was in late infancy (3 years), and sequencing in the affected children revealed a novel homozygous c.613C>T change in exon 3 of ceroid-lipofuscinosis, neuronal 5, corresponding to a missense mutation of a conserved amino acid, p.Pro205Ser. The clinical manifestations of the disease in this family largely resemble those of ceroid-lipofuscinosis, neuronal 5 disease, variant late infantile that was first described in Finland and include mental decline, visual deterioration, ataxia, and epileptic seizures. This description of ceroid-lipofuscinosis, neuronal 5 disease in an Arab family adds to the clinical and molecular diversity of the variant late-infantile neuronal ceroid lipofuscinoses, which were originally reported in Europe and are increasingly recognized in other populations.

We report the results of a study carried out to delineate genetic and epidemiological aspects of homocystinuria in the Qatari population. Sixty-four patients with homocystinuria (37 males, 27 females, age 1 to 29 years) from 31 nuclear families were ascertained over a period of more than four years. The incidence of homocystinuria in Qatar was calculated to be ≥1:3000, the highest in the world known so far. All patients in whom data were available were vitamin B6-nonresponsive. Molecular studies were performed in all patients. All 53 patients from tribe M and all three patients from tribe K were homozygous for the mutation c.1006C>T (p.R336C) in the CBS gene, with an additional seven patients resulting from mixed marriages between tribe M and tribe K. A single patient from tribe S was homozygous for mutation c.700G>A (p.D234N) in the CBS gene. Both mutations have been previously reported but involve hypermutable CpG dinculeotides and may be recurrent mutations in the Qatari population. The results of this study illustrate a strong founder effect causing a high prevalence of an autosomal recessive disease in a highly consanguineous Arabian population. Molecular neonatal screening may be suitable for early detection of homocystinuria in this population. © 2006 Wiley-Liss, Inc.

To study the changes in the epidemiology, clinical and bacteriological profiles of bacterial meningitis in the era of the Haemophilus influenzae type b (Hib)vaccine and pneumococcus resistance.This is a retrospective study of children aged12 years admitted to the Hamad Medical Corporation, Qatar between January 1998 through December 2002 with positive cerebrospinal fluid culture.We described 64 patients with culture proven bacterial meningitis. In infants3 months (n=29 [45%]), the most common organism was Group B Streptococcus (GBS) (20%). Children3 months (n=35 [55%]); Hib (25%) and Streptococcus pneumoniae (STP) (20%) were the most common organisms before introduction of Hib vaccination. A significant drop of Hib infections were noticed after introduction of the vaccine. Fever, neck stiffness, seizure, vomiting, and bulging fontanel were the most frequent presenting features. Group B Streptococcus were sensitive to ampicillin and cefotaxime with no resistance detected. Forty percent of STP isolates were resistant to penicillin and 12% were resistant to ceftriaxone. Fifty percent of Hib were resistant to ampicillin; while none of Hib were resistant to ceftriaxone. No case of Listeria monocytogenes meningitis was diagnosed. Morbidity was 28%, and one patient expired (2%) after Klebsiella pneumoniae meningitis. Streptococcus pneumoniae was associated with the highest morbidity (62%) while Hib had zero morbidity in our patients.Bacterial meningitis is a serious illness with a significant morbidity and mortality. Haemophilus influenzae type b infection decreased which indicated an effective vaccination. As there is 12% bacterial resistance of STP reported against ceftriaxone; We recommend Cefotaxime for infants3 months while ceftriaxone plus vancomycin as empiric therapy for older patients with community acquired bacterial meningitis. A pneumococcal vaccination may further decrease the incidence of meningitis in our community. A continuos surveillance to detect changes in the microbiology of organisms causing bacterial meningitis or their sensitivity in our community is essential to update these recommendations.

The aim of this study is to determine the prevalence rate and impact of headache in school children on school attendance with particular attention to migraine.A cross sectional survey was conducted among the school children ranging from 6-17 years old over a period from March 2001 to April 2003. The study was carried out in 10 primary, preparatory and secondary schools. Subjects were selected by multistage stratified sampling procedure. This involved 851 children studying in the first to tenth year of school in the State of Qatar.The present study showed that the prevalence rate of recurrent headache was 85% and migraine 11.9%. Comparing gender frequency of headache, it was noted that it was higher in female students (86.5%) than males (81%). In respect of age, it was observed that the oldest children had more frequent episodes of headache, the highest rate was in the age group of 11-15 years old (49%). The most common triggers were fatigue (35.8%) and lack of sleep (17.6%). The most common symptoms that occurred before headache were change in mood for female students (39.1%) and blurred vision for males (34.6%). The impact of headache on children was frequent absence from school (80%), which affected their school performance.The current study indicated the high prevalence of headache among school children in Qatar, and its effect on school attendance and performance.

We report a female premature infant with bronchopulmonary dysplasia and Sandhoff disease. The clue for diagnosis was the fundoscopy examination. We discuss this rare disease with unusual presentation of intrauterine growth retardation, premature delivery, and bronchopulmonary dysplasia.

Opsoclonus myoclonus syndrome (OMS) is a very rare syndrome which presents with ataxia, opsoclonus and myoclonus. We report the combined treatment of immunoglobulins and prednisolone compared to prednisolone alone in two patients. The diagnosis was based on the clinical findings. Work up for neuroblastoma was negative in both patients. Prednisolone treatment in the first patient was associated with slow response, relapses and toxic side effects. Immunoglobulins combined with prednisolone in the second patient were effective with neither relapse nor drug side effect. The clinical findings, differential diagnosis and the management are discussed. It appears that combined therapy with prednisolone and immunoglobulin gives better results. To the best of our knowledge this is first paper from the Middle East reporting this syndrome.