Clinical, Biochemical, and Molecular Characterization of Metachromatic Leukodystrophy Among Egyptian Pediatric Patients: Expansion of the ARSA Mutational Spectrum.

Metachromatic leukodystrophy (MLD) is a neurodegenerative disorder characterized by progressive demyelination due to deficiency of the enzyme arylsulfatase A (ARSA) in leukocytes, and consequently leads to impaired degradation and accumulation of cerebroside-3-sulfate (sulfatide). This study aimed to sequence the ARSA gene in a total of 43 patients with metachromatic leukodystrophy descendant from 40 Egyptian families. In addition, four carrier parents from two families with children who had died from MLD came to the clinic for genetic analysis. Prenatal diagnosis was performed for four families with molecularly diagnosed MLD sibs. Different mutations were characterized in our cohort, including missense, nonsense, splice, and deletion. Overall, 21 different mutations in the ARSA gene were detected, with 12 novel mutations, i.e. p.Arg60Pro, p.Tyr65*, p.Val112Asp, p.Arg116*, p.Gly124Asp, p.Pro193Ser, p.Gln238*, p.Gln456*, p.Thr276Lys, and p.Gly311Arg, in addition to two new acceptor splice-site mutations 685-1G > A and c.954_956 delCTT. The amniotic fluid samples revealed two carrier fetuses with heterozygous monoallelic mutations, and two affected fetuses had the homozygous biallelic mutations. In conclusion, the current study sheds light on the underlying ARSA gene defect, with an expansion of the mutation spectrum. To our knowledge, this is the first molecular study of MLD among the Egyptian population.

Apical extrusion of debris with different rotary and reciprocating single-file endodontic instrumentation systems: a systematic review and meta-analysis protocol.

INTRODUCTION: Root canal treatment is one of the oldest dental procedures for the treatment of endodontic infection. Extrusion of debris beyond the root apex during root canal instrumentation and subsequent persistence of pain are common complications. A systematic review of the evidence on reciprocating single-file instrumentation systems and their comparison with rotary single-file systems, with apical extrusion of debris as primary outcome, will be done through this study. METHODS AND ANALYSIS: Published ex vivo and in vitro studies with no language restriction will be included. We will search MEDLINE (Ovid), EMBASE (Ovid), Web of Science, Cochrane and Google Scholar. Strategies will be incorporated to search grey literature also. Thorough evaluation of search results, completion of data abstraction and assessment of quality will be done by two reviewers independent from each other. Assessment of included studies will be done by utilising an evidence model developed on the basis of standards of quality reported in guidelines to document ex vivo and in vitro studies regarding dental materials and pertained for extrusion of debris apically and has been already used in quality assessment of studies involving quantification of debris extrusion apically. We will calculate the standardised mean differences for apically extruded debris, with congruent 95% CIs. We will measure the statistical heterogeneity by applying the Cochrane Q test and quantify using the I2 statistic. Existence of covariates and any potential heterogeneity will be explored through prespecified subgroup and sensitivity analyses. ETHICS AND DISSEMINATION: Approval from an ethical research committee is not required because it will be done using data that have been already published and have no concerns related to the privacy of patients. Extensive dissemination of results from this review will be done through submission to a peer-reviewed journal for publication and conferences. PROSPERO REGISTRATION NUMBER: CRD42019151804.

Calcific Metamorphosis: A Review.

Dental trauma to the permanent dentition can lead to clinical complications and its management may considerably challenge a practitioner. The incidence of pulp canal obliteration following dental trauma has been reported to be approximately 4 - 24%. Attempting to locate canals following calcific metamorphosis and negotiating it to full working length may lead to iatrogenic errors such as fractured instrument and perforation. This review article describes the possible etiology of Calcific Metamorphosis, its clinical and radiographic features as well as its management.