Neurometabolic disorders are hereditary diseases of which neurological manifestations are a prominent sign. Because some neurometabolic diseases are treatable, early detection and early intervention ...in patients are essential. Children without early diagnosis and treatment suffer recurrent episodes of lethargy and loss of consciousness due to environmental stresses, and these attacks can lead to metabolic decompensating and often have fatal effects. Severe neurological consequences or regression in neurodevelopmental milestones are prominent signs in patients who survive.According to these findings, physicians--especially in the fields of pediatric neurology, pediatric endocrinology, as well as pediatrics and neurology more generally--need to be familiar with these important groups of disorders in order to diagnose and treat them successfully. This atlas of neurometabolic disorders can be used as a guide, and is recommended for all pediatric specialists wishing to provide early diagnoses of pediatric patients.
Pathogenic mutations in the FARSB gene are associated with neurodevelopmental disorder involving the brain, liver, and lungs. We report genetic analysis of a family including two affected members ...with this disorder, which revealed a homozygous pathogenic missense variant, FARSB: NM_005687.4:c.853G > A:p.E285K in both affected patients. The parents were heterozygous for this variant.
Early diagnosis of atypical cases of FARSB mutation in children with multisystem disorders provides the chance to imply novel treatments for them as well as carrier detection and prenatal diagnosis. Therefore, performing genetic test such as Whole Exome Sequencing could help us in this regard.
Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. The signs and symptoms of NP-C vary with age at disease onset, ...and available therapies are directed at alleviating symptoms and stabilizing disease progression. We report the characteristics and factors related to disease progression, and analyze the effect of miglustat treatment on disease progression and patient survival using NP-C disability scales.
This retrospective, observational chart review included patients with NP-C from five expert NP-C centers. Patient disability scores were recorded using three published NP-C disability scales, and a unified disability scale was developed to allow comparison of data from each scale. Disease progression was represented by scores on the unified NP-C disability scale. Patients were stratified as infantile (< 4 years), juvenile (≥ 4 - < 16 years), and adult (≥ 16 years) based on age at diagnosis, and treated ≥1 year and non-treated/treated < 1 year based on the duration of miglustat treatment.
The analysis included 63 patients; the majority (61.9%) were on miglustat therapy for ≥1 year. Ataxia and clumsiness/frequent fall were the most common neurologic symptoms across age groups, whereas, hypotonia and delayed developmental milestones were specific to infantile patients. In both infantile and juvenile patients, visceral signs preceded diagnosis and neurologic signs were noted at or shortly after diagnosis. Adult patients presented with a range of visceral, neurologic, and psychiatric signs in years preceding diagnosis. Patients on miglustat therapy for ≥1 year had a lower mean annual disease progression compared with those untreated/treated < 1 year (1.32 vs 3.54 points/year). A significant reduction in annual disease progression in infantile patients, and a trend towards reduced disease progression in juvenile patients after ≥1 year of miglustat treatment, translated into higher age at last contact or death in these groups.
The type and onset of symptoms varied across age groups and were consistent with descriptions of NP-C within the literature. Miglustat treatment was associated with a reduced rate of disability score worsening in infantile and juvenile patients, both in agreement with increased age at last contact.
Background and Aim: Questionnaires are useful tools for clinicians. This study aimed to translate the Dizziness Handicap Inventory for Patient Caregivers (DHI-PC) into Persian (DHI-PC-P) and assess ...its psychometric properties for children aged 5–12 years.
Methods: This is a descriptive-analytical psychometrics study. After obtaining permission from the developers of the DHI-PC, translation into Persian and cross-cultural adaptation were done according to the international guidelines for self-assessment tools recommended by the American Association of Orthopedic Surgeons. Participants were 21 parents (mean age: 38.05 years, SD=6.1 years, 18 female) and their children with dizziness (mean age
8.69 years, SD=2.41 years, 9 female) between the ages of 5–12 years old. Face validity, content validity, and test-retest reliability at an interval of 14–21 days were evaluated for the DHI-PC-P.
Results: The face validity was confirmed qualitatively by the experts’ opinions and quantitatively by calculating the item impact score. Content validity was confirmed by calculating the content validity index and the content validity ratio (0.97 and 0.86, respectively). The internal consistency was good (Cronbach’s alpha=0.90). For the test- retest reliability, the intraclass correlation coefficient was obtained 0.94, indicating an excellent reliability.
Conclusion: The DHI-PC-P can be used clinically as a valid and reliable tool for children with dizziness aged 5–12 years.
Keywords: Questionnaire; dizziness handicap inventory; validity; reliability; vertigo; children
Lysosomal storage diseases (LSDs) are known as genetic disorders with an overall prevalence of 1 per 7700 live births. Sphingolipidosis, which is a subgroup of LSDs, is resulted from mutations in the ...coding genes of specific enzymes of sphingolipid hydrolases. The current study aimed to provide additional knowledge on the genotype of sphingolipidoses disease among Iranian patients affected by the disease. In this research, we studied 68 unrelated Iranian patients diagnosed with one kind of sphingolipidoses from 2014 to 2019. Thereafter, genomic DNA was isolated from their peripheral blood leukocytes samples in EDTA in terms of the manufacturer’s protocol. All the coding exons and exon–intron boundaries of the related genes were sequenced and then analyzed using the NCBI database. Finally, they were reviewed using some databases such as the Human Gene Mutation Database (HGMD) and ClinVar (
https://www.ncbi.nlm.nih.gov/clinva
). By studying 22 MLD patients, 18 different variations of the
ARSA
gene were found, one of which was new including, named as c.472 T > G p. (Cys158Gly). Out of 15 Sandhoff disease (SD) patients, 11 different variations of the
HEXB
gene were found. Correspondingly, the c.1083-2delA was not reported earlier. By investigating 21 Iranian patients with Tay-Sachs disease (TSD), one new variant was found as c.622delG. The study of 10 Niemann–Pick disease A/B (NPDA/B (patients has led to the identification of 9 different
SMPD1
gene variations, among which 3 variations were novel mutations. The results of the present study can be expanded to the genotypic spectrum of Iranian patients with MLD, SD, TSD, and NPD diseases and also used to innovate more effective methods for the detection of genetic carriers as well as diagnosing and counseling of Iranian patients affected with these disorders.
To evaluate the prevalence of positive serum antinuclear antibody (ANA) in children with epilepsy using three major antiepileptic drugs (phenytoin, carbamazepine and ethosuximide), 60 children under ...18 years with epilepsy who were referred to pediatric neurology clinic or had admitted to neurology ward in Children Hospital in Tehran, Iran, were entered our study. They had been treated with one of the three antiepileptic drugs (carbamazepin, phenytoin, ethosuximide) with suitable dose for at least one month. The patients were divided into two groups according to the classification of the International League Against Epilepsy (ILAE): drug-resistant and drug-responsive. We studied the epidemiological and clinical characteristics and also serum ANA of the patients in both groups. In this research, we studied ANA in 60 epileptic children. 30 patients were diagnosed with drug resistant epilepsy and the other 30 were drug responsive. None of them showed the clinical manifestations of lupus erythematosus. As a whole, 7 patients (11.7%) were ANA-positive, 6.7% of drug resistant and 16.7% of drug responsive group showed this finding. There was no relationship between drug resistancy and ANA according to statistical studies (P=0.21). Although in our study, epidemiological and clinical data of the patients was reported in two separate groups of resistant or responsive to antiepileptic drugs, and no meaningful statistical difference was found between these two groups. Overally in our study, the prevalence of positive ANA in patients receiving antiepileptic drugs was less in comparison with previous studies and was more common in males. Finally, we suggest a more comprehensive and extensive study with more cases and further follow-up period in order to find the cause of immunological reactions to antiepileptic drugs in children with epilepsy.
Sleep disturbances are common in childhood and adolescence. Sleep problems in early infants tend to be persistent and prominent in preschool and school-aged children. Chronic sleep disorders, ...especially in young children may lead to neurobehavioral problems and psycho-cognitive impairment. Sleep difficulties may be the result of underlying medical conditions, （breathing disorders） or psychological problems. Research studies have shown the association between sleep disorders and day time cognitive impairment, behavioral problems, poor school performance and inattention in children. Appropriate diagnosis and early management of sleep disorders in children lead to improvement of neurocognitive function and behavioral problems in these children.
Pontocerebellar hypoplasia is an umbrella term describing a heterogeneous group of prenatal neurodegenerative disorders mostly affecting the pons and cerebellum, with 17 types associated with 25 ...genes. However, some types of PCH lack sufficient information, which highlights the importance of investigating and introducing more cases to further elucidate the clinical, radiological, and biochemical features of these disorders. The aim of this study is to provide an in-depth review of PCH and to identify disease genes and their inheritance patterns in 12 distinct Iranian families with clinically confirmed PCH.
Cases included in this study were selected based on their phenotypic and genetic information available at the Center for Comprehensive Genetic Services. Whole-exome sequencing (WES) was used to discover the underlying genetic etiology of participants' problems, and Sanger sequencing was utilized to confirm any suspected alterations. We also conducted a comprehensive molecular literature review to outline the genetic features of the various subtypes of PCH.
This study classified and described the underlying etiology of PCH into three categories based on the genes involved. Twelve patients also were included, eleven of whom were from consanguineous parents. Ten different variations in 8 genes were found, all of which related to different types of PCH. Six novel variations were reported, including SEPSECS, TSEN2, TSEN54, AMPD2, TOE1, and CLP1. Almost all patients presented with developmental delay, hypotonia, seizure, and microcephaly being common features. Strabismus and elevation in lactate levels in MR spectroscopy were novel phenotypes for the first time in PCH types 7 and 9.
This study merges previously documented phenotypes and genotypes with unique novel ones. Due to the diversity in PCH, we provided guidance for detecting and diagnosing these heterogeneous groups of disorders. Moreover, since certain critical conditions, such as spinal muscular atrophy, can be a differential diagnosis, providing cases with novel variations and clinical findings could further expand the genetic and clinical spectrum of these diseases and help in better diagnosis. Therefore, six novel genetic variants and novel clinical and paraclinical findings have been reported for the first time. Further studies are needed to elucidate the underlying mechanisms and potential therapeutic targets for PCH.
Niemann-Pick disease type C (NPC) is a rare lysosomal neurovisceral storage disease caused by mutations in the NPC 1 (95%) or NPC2 (5%) genes. The products of NPC1 and NPC2 genes play considerable ...roles in glycolipid and cholesterol trafficking, which could consequently lead to NPC disease with variable phenotypes displaying a broad spectrum of symptoms.
In the present study 35 Iranian NPC unrelated patients were enrolled. These patients were first analysed by the Filipin Staining test of cholesterol deposits in cells for NPC diagnostics. Genomic DNA was extracted from the samples of peripheral blood leukocytes in EDTA following the manufacturer's protocol. All exon-intron boundaries and coding exons of the NPC1gene were amplified by polymerase chain reaction (PCR) using appropriate sets of primers. Thereafter, the products of PCR were sequenced and analysed using the NCBI database ( https://blast.ncbi.nlm.nih.gov/Blast.cgi ). The variants were reviewed by some databases including the Human Gene Mutation Database (HGMD) ( http://www.hgmd.cf.ac.uk/ac/index.php ) and ClinVar ( https://www.ncbi.nlm.nih.gov/clinvar (. Moreover, all the variants were manually classified in terms of the American College of Medical Genetics and Genomics (ACMG) guideline.
The sequence analysis revealed 20 different variations, 10 of which are new, including one nonsense mutation (c.406C > T); three small deletions, (c.3126delC, c.2920_2923delCCTG, and c.2037delG); and six likely pathogenic missense mutations, (c.542C > A, c.1970G > A, c.1993C > G, c.2821 T > C, c.2872C > G, and c.3632 T > A). Finally, the pathogenicity of these new variants was determined using the ACMG guidelines.
The present study aimed to facilitate the prenatal diagnosis of NPC patients in the future. In this regard, we identified 10 novel mutations, and verified that the majority of them occurred in six NPC1 exons (5, 8, 9, 13, 19, and 21), that should be considered with a high priority for Iranian patients' cost-effective evaluation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Type II or juvenile GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder, which is clinically distinct from infantile form of the disease by the lack of characteristic cherry-red ...spot and hepatosplenomegaly. The disease is characterized by slowly progressive neurodegeneration and mild skeletal changes. Due to the later age of onset and uncharacteristic presentation, diagnosis is frequently puzzled with other ataxic and purely neurological disorders. Up to now, 3-4 types of GM1-gangliosidosis have been reported and among them type I is the most common phenotype with the age of onset around 6 months. Various forms of GM1-gangliosidosis are caused by GLB1 gene mutations but severity of the disease and age of onset are directly related to the position and the nature of deleterious mutations. However, due to its unique genetic cause and overlapping clinical features, some researchers believe that GM1 gangliosidosis represents an overlapped disease spectrum instead of four distinct types.
Here, we report a less frequent type of autosomal recessive GM1 gangliosidosis with perplexing clinical presentation in three families in the southwest part of Iran, who are unrelated but all from "Lurs" ethnic background. To identify disease-causing mutations, Whole Exome Sequencing (WES) utilizing next generation sequencing was performed. Four patients from three families were investigated with the age of onset around 3 years old. Clinical presentations were ataxia, gate disturbances and dystonia leading to wheelchair-dependent disability, regression of intellectual abilities, and general developmental regression. They all were born in consanguineous families with no previous documented similar disease in their parents. A homozygote missense mutation in GLB1 gene (c. 601 G > A, p.R201C) was found in all patients. Using Sanger sequencing this identified mutation was confirmed in the proband, their parents, grandparents, and extended family members, confirming its autosomal recessive pattern of inheritance.
Our study identified a rare pathogenic missense mutation in GLB1 gene in patients with complex neurodevelopmental findings, which can extend the list of differential diagnoses for childhood ataxia in Iranian patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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