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1.
Neurogenetics ; 24(4): 279-289, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37597066

RESUMO

Leukodystrophies (LDs) are a heterogeneous group of progressive neurological disorders and characterized by primary involvement of white matter of the central nervous system (CNS). This is the first report of the Iranian LD Registry database to describe the clinical, radiological, and genomic data of Persian patients with leukodystrophies. From 2016 to 2019, patients suspicious of LDs were examined followed by a brain magnetic resonance imaging (MRI). A single gene testing or whole-exome sequencing (WES) was used depending on the neuroradiologic phenotypes. In a few cases, the diagnosis was made by metabolic studies. Based on the MRI pattern, diagnosed patients were divided into cohorts A (hypomyelinating LDs) versus cohort B (Other LDs). The most recent LD classification was utilized for classification of diagnosed patients. For novel variants, in silico analyses were performed to verify their pathogenicity. Out of 680 registered patients, 342 completed the diagnostic evaluations. In total, 245 patients met a diagnosis which in turn 24.5% were categorized in cohort A and the remaining in cohort B. Genetic tests revealed causal variants in 228 patients consisting of 213 variants in 110 genes with 78 novel variants. WES and single gene testing identified a causal variant in 65.5% and 34.5% cases, respectively. The total diagnostic rate of WES was 60.7%. Lysosomal disorders (27.3%; GM2-gangliosidosis-9.8%, MLD-6.1%, KD-4.5%), amino and organic acid disorders (17.15%; Canavan disease-4.5%, L-2-HGA-3.6%), mitochondrial leukodystrophies (12.6%), ion and water homeostasis disorders (7.3%; MLC-4.5%), peroxisomal disorders (6.5%; X-ALD-3.6%), and myelin protein disorders (3.6%; PMLD-3.6%) were the most commonly diagnosed disorders. Thirty-seven percent of cases had a pathogenic variant in nine genes (ARSA, HEXA, ASPA, MLC1, GALC, GJC2, ABCD1, L2HGDH, GCDH). This study highlights the most common types as well as the genetic heterogeneity of LDs in Iranian children.


Assuntos
Doenças Desmielinizantes , Doenças Neurodegenerativas , Humanos , Criança , Irã (Geográfico) , Heterogeneidade Genética , Imageamento por Ressonância Magnética , Encéfalo , Oxirredutases do Álcool
2.
Cerebellum ; 22(4): 640-650, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35731353

RESUMO

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is now increasingly identified from all countries over the world, possibly rendering it one of the most common autosomal recessive ataxias. Here, we selected patients harboring SACS variants, the causative gene for ARSACS, in a large cohort of 137 patients with early-onset ataxia recruited from May 2019 to May 2021 and were referred to the ataxia clinic. Genetic studies were performed for 111 out of 137 patients (81%) which led to a diagnostic rate of 72.9% (81 out of 111 cases). Ten patients with the molecular diagnosis of ARSACS were identified. We investigated the phenotypic and imaging spectra of all confirmed patients with ARSACS. We also estimated the frequency of ARSACS in this cohort and described their clinical and genetic findings including seven novel variants as well as novel neuroimaging findings. While the classic clinical triad of ARSACS is progressive cerebellar ataxia, spasticity, and sensorimotor polyneuropathy, it is not a constant feature in all patients. Sensorimotor axonal-demyelinating neuropathy was detected in all of our patients, but spasticity and extensor plantar reflex were absent in 50% (5/10). In all patients, brain magnetic resonance imaging (MRI) showed symmetric linear hypointensities in the pons (pontine stripes) and anterior superior cerebellar atrophy as well as a hyperintense rim around the thalami (thalamic rim). Although infratentorial arachnoid cyst has been reported in ARSACS earlier, we report anterior temporal arachnoid cyst in two patients for the first time, indicating that arachnoid cyst may be an associated imaging feature of ARSACS. We also extended molecular spectrum of ARSACS by presenting 8 pathogenic and one variant of unknown significance (VUS) sequence variants, which 7 of them have not been reported previously. MetaDome server confirmed that the identified VUS variant was in the intolerant regions of sacsin protein encoded by SACS.


Assuntos
Ataxia Cerebelar , Cistos , Ataxias Espinocerebelares , Humanos , Irã (Geográfico) , Mutação/genética , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/genética , Espasticidade Muscular/diagnóstico por imagem , Espasticidade Muscular/genética , Neuroimagem
3.
BMC Neurol ; 22(1): 123, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351020

RESUMO

INTRODUCTION: The current multi-center, randomized, double-blind study was conducted among children with cerebral palsy (CP) to assess the safety and efficacy of umbilical cord blood mononuclear cell (UCB-MNC). We performed the diffusion tensor imaging to assess the changes in the white matter structure. METHODS: Males and females aged 4 to 14 years old with spastic CP were included. Eligible participants were allocated in 4:1 ratio to be in the experimental or control groups; respectively. Individuals who were assigned in UCB-MNC group were tested for human leukocyte antigen (HLA) and fully-matched individuals were treated with UCB-MNCs. A single dose (5 × 106 /kg) UCB-MNCs were administered via intrathecal route in experimental group. The changes in gross motor function measure (GMFM)-66 from baseline to one year after treatment were the primary endpoints. The mean changes in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also evaluated and compared between groups. The mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR) were the secondary endpoints. Adverse events were safety endpoint. RESULTS: There were 72 included individuals (36 cases in each group). The mean GMFM-66 scores increased in experimental group; compared to baseline (+ 9.62; 95%CI: 6.75, 12.49) and control arm (ß: 7.10; 95%CI: 2.08, 12.76; Cohen's d: 0.62) and mean MAS reduced in individuals treated with UCB-MNCs compared to the baseline (-0.87; 95%CI: -1.2, -0.54) and control group (ß: -0.58; 95%CI: -1.18, -0.11; Cohen's d: 0.36). The mean PEDI scores and mean CP-QoL scores in two domains were higher in the experimental group compared to the control. The imaging data indicated that mean FA increased and MD decreased in participants of UCB-MNC group indicating improvements in white matter structure. Lower back pain, headaches, and irritability were the most common adverse events within 24 h of treatment that were related to lumbar puncture. No side effects were observed during follow-up. CONCLUSIONS: This trial showed that intrathecal injection of UCB-MNCs were safe and effective in children with CP. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ( NCT03795974 ).


Assuntos
Paralisia Cerebral , Adolescente , Criança , Pré-Escolar , Imagem de Tensor de Difusão/métodos , Método Duplo-Cego , Feminino , Sangue Fetal , Humanos , Masculino , Qualidade de Vida
5.
J Trop Pediatr ; 62(4): 269-75, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26995012

RESUMO

BACKGROUND: Obesity seems to be a critical issue nowadays because of its high prevalence and its adverse effects on health. There is some evidence indicating the relationship between obesity and lower serum 25-hydroxyvitamin D [25(OH)D] concentration. The aim of the present study was to examine serum 25(OH)D status of obese and non-obese Iranian children and compare their therapeutic response with identical oral vitamin D3 treatment. METHODS: In a non-randomized clinical trial, serum 25(OH)D level of 45 obese and 45 non-obese Iranian children aged 2-14 years was measured. Those with serum 25(OH)D status <30 ng/ml (73 cases) were treated with one pearl of vitamin D3 (50 000 International Units) once a week for 6 weeks. Serum vitamin D was measured once more 2 weeks after treatment. RESULTS: The frequency of hypovitaminosis D was 43/45 (95.6%) in obese and 30/45 (66.7%) in non-obese children at baseline (p < 0.001). After treatment of 73 cases (43 obese, 30 non-obese), the above percentages were decreased to 24/43 (55.8%) and 1/30 (3.3%), respectively (p < 0.001). CONCLUSION: Our study demonstrated a high frequency of vitamin D deficiency among Iranian children, particularly the obese ones. Moreover, low therapeutic response in the obese group is witnessed.


Assuntos
Adiposidade/fisiologia , Colecalciferol/administração & dosagem , Colecalciferol/uso terapêutico , Obesidade/sangue , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D/análogos & derivados , Vitaminas/uso terapêutico , Adiposidade/etnologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Obesidade/etnologia , Prevalência , Raquitismo/sangue , Raquitismo/etnologia , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etnologia , Vitaminas/administração & dosagem
6.
Mol Syndromol ; 15(1): 30-36, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38357261

RESUMO

Introduction: TPP1 variants have been identified as a causative agent of neuronal ceroid lipofuscinosis 2 disease, that ataxia is one of its clinical features. Therefore, here, molecular study of TPP1 variants is presented in an Iranian cohort and a novel pathogenic variant is described. Methods: This investigation was conducted as a cross-sectional study in a tertiary referral hospital, Children's Medical Center, Pediatrics Center of Excellence. Clinical presentations and pedigrees were documented. Patients with cerebellar ataxia were enrolled in this study. Next-generation sequencing was applied to confirm the diagnosis. Segregation and bioinformatics analyses were also done for the variants using Sanger sequencing. Results: Forty-five patients were included in our study. The mean age of onset was 104 (+55.60) months (minimum = 31 months, maximum = 216 months). The majority of cases (73.3%) were born to consanguineous parents and only 1 patient (2.2%) had an affected sibling. Of the 45 patients, only 1 patient with a novel pathogenic variant (c.1425_1425+1delinsAT, p.A476Cfs*15) in the TPP1 gene was identified. Discussion: The main strength of current study is the relatively large sample size. Besides, a novel pathogenic variant could be important toward the diagnosis and management of this condition. With significant advances in various therapies, early diagnosis could improve the treatments using personalized-based medicine.

7.
Pediatr Diabetes ; 14(5): 366-71, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22583516

RESUMO

Specific alleles at the HLA-DRB1, -DQA1, and -DQB1 loci seem to be associated with variable risks of developing type 1 diabetes (T1D). This study assessed the distribution of HLA-DR and -DQ alleles among Iranian T1D patients and healthy controls. In this study, HLA-DRB1, -DQA1, and -DQB1 alleles were determined in 100 children with T1D and 100 unrelated healthy controls. The following alleles were found to have a strong positive association with T1D: DRB1*0301, DRB1*0401, DRB1*0402, DQA1*0301, DQA1*0501, DQB1*0201, and DQB1*0302. Meanwhile, protective associations were found for DRB1*1001, DRB1*1101, DRB1*15, DRB1*16, DQA1*0102, DQA1*0103, DQB1*0301, DQB1*0501, and DQB1*0602 alleles. The haplotypes found most frequently among patients with T1D were DRB1*0301-DQA1*0501-DQB1*0201, DRB1*0401-DQA1*0301- DQB1*0302, and DRB1*0402-DQA1*0301-DQB1*0302, whereas DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*16-DQA1*0102- DQB1*0501 haplotypes were negatively associated with the disease. These results confirm the previously reported association of specific HLA-DR and HLA-DQ alleles and haplotypes with T1D in Iranian population. The notable difference was the identification of DRB1*16-DQA1*0102-DQB1*0501 as a protective haplotype and the absence of a negative association of DRB1*1301-DQA1*0103-DRB1*0603 with T1D.


Assuntos
Diabetes Mellitus Tipo 1/genética , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Adolescente , Alelos , Criança , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/etnologia , Feminino , Frequência do Gene , Haplótipos , Humanos , Irã (Geográfico)/epidemiologia , Masculino , População Branca/genética
8.
Int J Prev Med ; 14: 11, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36942039

RESUMO

Congenital hypothyroidism (CH) is one of the most treatable endocrine disorders in infants and children that can influence the function of many organs in the body. On-time diagnosis and treatment can prevent the adverse effects of thyroid hormone deficiency on the child's neurodevelopment. There are many challenges in screening, post-screening, diagnosis, and managing this disorder. Therefore, this article aimed to mention updated information on this issue. Although there are different approaches for the treatment of hypothyroidism, the authors decided to create a national approach based on the conditions of our country.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35975869

RESUMO

BACKGROUND: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder. This study aimed to investigate whether disturbances in amino acid metabolism and fatty acid oxidation existed in neonates with CH compared to healthy neonates. METHODS: In this case-control study, we evaluated the metabolomics of neonates with newly diagnosed CH and healthy neonates. Forty-three metabolites, including 13 amino acids and 30 acylcarnitines, were investigated. RESULTS: Two hundred neonates with CH and 209 healthy children were enrolled. The mean age of males and females was 4.8 ± 2.4 and 5.52 ± 3.2 days in the case group and 5.1 ± 2.6 and 4.7 ± 3.6 days in the control group, respectively. Of the metabolites, 34 were significantly different between the two groups. Five amino acids and four acylcarnitines did not differ significantly between groups. CONCLUSION: These findings pave the way for a better understanding of the relationship between alterations and the clinical manifestation of CH, which has the potential for identifying novel therapeutics.


Assuntos
Aminoácidos , Hipotireoidismo Congênito , Masculino , Recém-Nascido , Criança , Feminino , Humanos , Hipotireoidismo Congênito/diagnóstico , Estudos de Casos e Controles , Carnitina
10.
Mediterr J Rheumatol ; 34(1): 44-52, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37223593

RESUMO

Background and Objective: Given the growing awareness about the important role of children's age in building bone for a person's life, physicians need to assess bone health in high-risk children for bone density disorders more than before to optimize their bones' density and prevent osteoporosis in future. The aim of this study was to evaluate bone density based on chronological and bone age. Materials and Methods: In this cross-sectional study, 80 Patients who have been referred for bone density to the Osteoporosis Centre of the Children's Medical Centre over a one-year period (spring 98 to spring 99) were studied. Bone density was performed for all patients by using DEXA method. Results: The z-score mean chronological age for the lumbar spine was -0.8± 1.85 years and bone age was -0.58±1.64 years. The z-score mean chronological age for femoral bone was -1.6±1.02 years and bone age was -1.32± 1.4 years. Conclusion: Results showed that in all patients, the difference in the mean Z score of chronological age and bone age of the spine between patients was not significant but for femur was significant. Also, use of corticosteroids leads to significant difference between the two age groups' z-score in femur and spine.

11.
Clin Lab ; 58(9-10): 1063-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23163125

RESUMO

The incidence of Congenital Adrenal Hyperplasia (CAH) is 1:10,000 - 16,000 worldwide, of which 90% occurs in the CYP21A2 gene coding for steroid 21-hydroxylase. On the other hand, Turner's syndrome, with an incidence of 1:2500, is a form of gonadal dysgenesis which leads to early ovarian failure and other phenotypic changes such as webbed neck, widely-spaced nipples and short stature. Here, we present a girl suffering from both 45,X/46,XX Turner's syndrome and salt wasting (SW) form of CAH. Clinical and biochemical examinations were performed for the patient. Cytogentic studies and molecular testing such as allele specific PCR for eight mutations in the CYP21A2 gene, multiplex ligation probe amplification (MLPA) and direct sequencing confirmed the clinical diagnosis. Heterozygous mutations in the regulatory region at positions -316 to -264 verified SW form of 21-hydroxylase deficiency. 45,X/46,XX mosaicism proved Turner's syndrome. The SW presentation of the patient may be due to the CYP21A1P microconversion. The study of regulatory changes of the CYP21A2 and gender differentiation pathways would be possible using such patients.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Cromossomos Humanos X/genética , Mosaicismo , Esteroide 21-Hidroxilase/genética , Síndrome de Turner/genética , Anormalidades Múltiplas , Adolescente , Hiperplasia Suprarrenal Congênita/enzimologia , Processamento Alternativo , Feminino , Humanos , Cariotipagem , Mutação , Cloreto de Sódio/metabolismo , Esteroide 21-Hidroxilase/metabolismo , Síndrome de Turner/enzimologia
12.
Turk J Pediatr ; 54(3): 309-11, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23094546

RESUMO

Despite the essential role of insulin in the management of patients with diabetes mellitus type 1, insulin use can cause a variety of adverse effects, such as hypoglycemia and weight gain. Herein, we describe an adolescent girl with type 1 diabetes mellitus diagnosed one year ago, who presented with edema of the lower extremities approximately two weeks after an increase in the insulin dose; other causes of edema were excluded. Spontaneous recovery was observed in the patient.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Edema/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Adolescente , Feminino , Humanos , Extremidade Inferior , Remissão Espontânea
13.
J Diabetes Metab Disord ; 21(2): 1255-1260, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36404836

RESUMO

Background: Obesity is a complicated phenomenon which is a combination of genetic, environmental, and psychological factors. Genetic factors of obesity play an important role in individual risk. It is well known that obese children have disturbed puberty timing. To the best of our knowledge, no study has been performed to investigate the association between MC4R gene mutation and puberty timing. Methods: This study was performed as a cross-sectional study evaluating the near MC4R rs17782313 variation in 60 obese children and 98 healthy non obese children. Weight, height, BMI ( Body Mass Index ), BMI z-score (BMIz), family history of diabetes mellitus and obesity, the age of the obesity onset, overeating behavior, type of obesity (central or general) and puberty stage were evaluated in 60 obese children. Results: The average age of the participants was 14.87 (+/- 1.3) years, with average weight and BMI of 90.77 (+/-12.2) Kg and 31.72 (+/-4.35) Kg/m2, respectively. Compared to healthy non obese patients, those with C-T genotype (C-T Vs. T-T and C-C) had higher odds of obesity than those with T-T and C-C genotype (p < 0.0001) while genotype TT showed significant protective effect (p = 0.0007). The heterozygote individuals (CT) have a higher BMIz than homozygote ones (CC and TT) (2.8 vs. 2.5 Kg/m2, p = 0.04). Conclusions: children with CT genotype have 5.1 increased risk of obesity. While genotype TT showed significant obesity protective effect. We did not find association of this polymorphism with either childhood eating disorders or puberty. It is recommended to perform a cohort study in a larger sample. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01011-5.

14.
Arch Physiol Biochem ; 128(5): 1209-1214, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32449378

RESUMO

Objective: This study is designed to investigate the levels of carnitine and acylcarnitines (ACs) in the children with diabetes type 1 compared to the healthy subjects.Methods: Forty-two type 1 diabetic children and healthy subjects were recruited in the study, respectively. In addition to FBS and Hb A1C, free carnitine and ACs in butyl-ester form in the fasting blood samples were assessed by isotope dilution mass spectrometry for all diabetics and controls using the tandem mass spectrometry system.Results: Diabetic patients had a higher level of C, C4, C6, C14, C18:2, and C18:2OH. Females had elevated C14:2 compared to the males. The C18:2 and C18:2OH levels were elevated as the Hb A1C level increased. The C18:2, C14OH were mostly increased in the prediabetic and diabetic patients, respectively.Conclusion: Increased ACs level indicates the increased acyl-CoA intermediates for the fatty acids and amino acids oxidation.


Assuntos
Diabetes Mellitus Tipo 1 , Aminoácidos , Carnitina/análogos & derivados , Carnitina/metabolismo , Criança , Coenzima A , Ésteres , Ácidos Graxos/metabolismo , Feminino , Hemoglobinas Glicadas , Humanos , Isótopos , Masculino
15.
Minerva Endocrinol (Torino) ; 47(2): 167-171, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-32744439

RESUMO

BACKGROUND: It has been hypothesized that puberty onset is disturbed as the children gain more weight. This study aimed to investigate the prevalence and risk factors of the puberty disturbances among children with obesity in Tehran, Iran. METHODS: This study was performed as a cross-sectional study, investigating 168 children with obesity from Tehran, Iran, from March 2018 to February 2019. BMI percentile more than 95% was considered as the inclusion criteria. RESULTS: Seventy-eight (46.4%) of the assessed children were females. The mean weight, height, BMI were 89.65 (±11.01) kg, 169.88 (±8.32) centimeters and 31.13(±3.8) kg/m2, respectively. There was no difference between males and females regarding the early puberty (P=0.098), but delayed puberty was significantly higher among males (P=0.029). Our results indicated higher birth weight is associated with earlier onset of obesity in children (P=0.044). CONCLUSIONS: Our study demonstrated no association between obesity and early puberty in girls; however, boys with obesity had delayed puberty. We also found higher birth weight is associated with earlier onset of obesity, putting light on the importance of preventive interventions.


Assuntos
Obesidade Infantil , Puberdade Tardia , Puberdade Precoce , Peso ao Nascer , Criança , Estudos Transversais , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Obesidade Infantil/epidemiologia , Puberdade Precoce/epidemiologia
16.
Stem Cell Res Ther ; 13(1): 264, 2022 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725652

RESUMO

BACKGROUND: Type-1 diabetes (T1D) occurs following autoimmune-induced pancreatic beta cells death. Among several treatment modalities, mesenchymal stem cells (MSCs) transplantation is promising for autoimmune disorders due to immunomodulation, regeneration, and migration to damaged tissue upon systemic injection. This study assessed the safety and efficacy of intravenous injection of autologous bone marrow-derived MSCs in newly diagnosed T1D patients. METHODS: After receiving informed consent, 21 patients who met the study criteria were enrolled and randomly assigned to receive either MSCs or placebo. Each patient in the experimental group received two doses of MSCs and was followed for at least one-year post-transplantation. RESULTS: The results have shown that this transplantation is safe and significantly reduces the number of hypoglycemic episodes. MSCs transplantation improved glycated hemoglobin (HbA1c), shifted serum cytokine patterns from pro-inflammatory to anti-inflammatory, increased the number of regulatory T-cells in the peripheral blood, and improved quality of life. Early transplantation of MSCs significantly improved HbA1c and C-peptide levels and shifted pro-inflammatory cytokines to anti-inflammatory cytokines. Also, exercise combined with MSCs transplantation improved glycemic and immunologic indices. CONCLUSIONS: Taken together, autologous MSC transplantation is safe and effective, and its early transplantation is a promising treatment in newly diagnosed T1D children suffering from hypoglycemic episodes. TRIAL REGISTRATION: This clinical trial was registered at the Iranian Registry of Clinical Trials (IRCT) with the identifier IRCT ID: IRCT2016070428786N1 registered on August 20, 2016 (Retrospectively registered) ( https://en.irct.ir/trial/23256 ) and at the U.S. National Institutes of Health (ClinicalTrials.gov) with the related identifier NCT04078308 registered on September 6, 2019 (Retrospectively registered). ( https://clinicaltrials.gov/ct2/show/NCT04078308 ).


Assuntos
Diabetes Mellitus Tipo 1 , Transplante de Células-Tronco Mesenquimais , Criança , Citocinas , Diabetes Mellitus Tipo 1/terapia , Hemoglobinas Glicadas , Humanos , Hipoglicemiantes , Irã (Geográfico) , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Qualidade de Vida
17.
Basic Clin Neurosci ; 12(4): 563-568, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35154596

RESUMO

INTRODUCTION: Allan-Herndon-Dudley Syndrome (AHDS) is a rare X-linked recessive intellectual disability condition with neuromuscular involvements. Altered thyroid function tests are major milestones in AHDS diagnosis. However, due to phenotypic variations in the levels of thyroid hormones in AHDS patients, we believe that the disorder is often underdiagnosed. Here, we reported a 3.5-year-old boy with an AHDS diagnosis and healthy thyroid hormones. METHODS: Whole-Exome sequencing followed by data analysis was performed on the patient's sample. The mutation was confirmed by Sanger sequencing in the patient and his mother. RESULTS: We reported a 3.5-year-old boy with AHDS diagnosis and a novel synonymous missense mutation (c. 1026G>A) in the SLC16A2 gene manifesting normal levels of T3, T4, and TSH. The mutation causes no change in amino acid sequence; however, it affects splicing through alteration of an exonic splicing enhancer. To the best of our knowledge, there are only 3 similar reports in the literature reporting AHDS diagnosis and normal levels of thyroid hormones. CONCLUSION: The altered levels of thyroid hormones are notable but not necessary markers for diagnosing AHDS. The candidate diagnosis of AHDS should be considered in patients with X-linked recessive intellectual disability syndrome with neuromuscular involvements irrespective of levels of thyroid hormones; otherwise, it could lead to the under-diagnosis of the disorder.

18.
Sci Rep ; 11(1): 3231, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547378

RESUMO

This study evaluates the genetic spectrum of leukodystrophies and leukoencephalopathies in Iran. 152 children, aged from 1 day to 15 years, were genetically tested for leukodystrophies and leukoencephalopathies based on clinical and neuroradiological findings from 2016 to 2019. Patients with a suggestive specific leukodystrophy, e. g. metachromatic leukodystrophy, Canavan disease, Tay-Sachs disease were tested for mutations in single genes (108; 71%) while patients with less suggestive findings were evaluated by NGS. 108 of 152(71%) had MRI patterns and clinical findings suggestive of a known leukodystrophy. In total, 114(75%) affected individuals had (likely) pathogenic variants which included 38 novel variants. 35 different types of leukodystrophies and genetic leukoencephalopathies were identified. The more common identified disorders included metachromatic leukodystrophy (19 of 152; 13%), Canavan disease (12; 8%), Tay-Sachs disease (11; 7%), megalencephalic leukodystrophy with subcortical cysts (7; 5%), X-linked adrenoleukodystrophy (8; 5%), Pelizaeus-Merzbacher-like disease type 1 (8; 5%), Sandhoff disease (6; 4%), Krabbe disease (5; 3%), and vanishing white matter disease (4; 3%). Whole exome sequencing (WES) revealed 90% leukodystrophies and genetic leukoencephalopathies. The total diagnosis rate was 75%. This unique study presents a national genetic data of leukodystrophies; it may provide clues to the genetic pool of neighboring countries. Patients with clinical and neuroradiological evidence of a genetic leukoencephalopathy should undergo a genetic analysis to reach a definitive diagnosis. This will allow a diagnosis at earlier stages of the disease, reduce the burden of uncertainty and costs, and will provide the basis for genetic counseling and family planning.


Assuntos
Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Leucodistrofia Metacromática/genética , Leucoencefalopatias/genética , Adolescente , Doença de Canavan/epidemiologia , Doença de Canavan/genética , Criança , Pré-Escolar , Feminino , Testes Genéticos , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/epidemiologia , Humanos , Lactente , Recém-Nascido , Irã (Geográfico)/epidemiologia , Leucodistrofia de Células Globoides/epidemiologia , Leucodistrofia de Células Globoides/genética , Leucodistrofia Metacromática/epidemiologia , Leucoencefalopatias/epidemiologia , Masculino , Mutação
19.
Clin Neurol Neurosurg ; 201: 106448, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33385934

RESUMO

OBJECTIVE: Metachromatic leukodystrophy (MLD) is an autosomal recessive leukodystrophy caused by deficiency of aryl sulfatase A (ASA) activity affecting the nervous system. MLD and mutations in ARSA have not been widely studied in non-European cohorts. The genotype-phenotype spectrum of MLD patients was investigated in this study of a cohort of Iranian leukodystrophy patients. In silico analysis was performed to investigate the pathogenicity of the variants. METHODS: Genetic analysis for 25 patients was performed with direct sequencing of the ARSA gene. The missense variants underwent in silico analysis to characterize the pathogenicity based on predicted structural and stability changes. RESULTS: 19 patients had variants in ARSA genes, including 18 homozygotes and one compound heterozygote individual. In 6 individuals no mutations were found in ARSA gene, suggesting an alternative cause of their leukodystrophy. We found 5 novel disease causing variants: p.Phe64Ile, p.Ser292Alafs*34, p.Arg99Profs*35, p.Phe400Leu and p.Leu429Pro. 32 % of the patients had p.Gly311Ser substitution and resulted in juvenile MLD type. Different in silico analysis showed variable pathogenic effect for the variants. CONCLUSION: c.931 G > A (p.Gly311Ser) and c.465 + 1 G > A variants are the most frequent alleles among Iranian MLD patients and five mutations appear to be confined to the Iranian patients. Population screening for these variants may be helpful to reduce the burden of the disease in this part of the world.


Assuntos
Cerebrosídeo Sulfatase/genética , Leucodistrofia Metacromática/genética , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Estudos de Associação Genética , Humanos , Lactente , Irã (Geográfico) , Masculino , Mutação de Sentido Incorreto
20.
Front Pediatr ; 9: 582043, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956968

RESUMO

Objective: Previous studies have demonstrated that both children and adult patients with a history of congenital heart disease (CHD) are at high risk for coronavirus disease 2019 (COVID-19) infection. This study investigates the status of COVID-19 infection among children undergoing surgical repair within the past 2 years. Methods: All alive patients operated on in a tertiary referral center between March 2018 and March 2020 were recruited in the present study. Detailed demographics, past medical and surgical history, and physical examination were reviewed for each patient. During the COVID-19 pandemic, data regarding the patient's status were collected by telephone survey from April 15 to April 30, 2020. Results: A total number of 210 patients are analyzed in this study. Participants' median age was 21.59 months [interquartile range (IQR) = 12-54.67], and 125 (59.5%) were female. The median interval between surgery and COVID-19 assessment was 305 days (IQR = 215-400). In addition, 67 (32%) patients used angiotensin receptor blocker (ARB)/angiotensin-converting enzyme (ACE) inhibitor (spironolactone and/or captopril). Sixteen patients (7.6%) were symptomatic and had positive chest CT results and/or RT-PCR compared to the previously reported prevalence of COVID-19 among the pediatric population (2.4% of children with <18 years of age); the prevalence of COVID-19 among the patients operated on due to CHD in the present study was significantly higher (p = 0.00012). Two patients were admitted to the intensive care unit (ICU); one patient was discharged 2 weeks later with acceptable status, and one patient died 2 days after ICU admission due to cardiac and respiratory arrest and myocarditis. The complexity of the underlying cardiac disorders was not different between patients with low risk (p = 0.522), suspicious patients (p = 0.920), and patients positive for COVID-19 (p = 0.234). The ARB/ACE inhibitor consumption was not associated with the COVID-19 infection [p = 0.527, crude odds ratio (OR) = 1.407, 95% CI = 0.489-4.052]. Conclusion: Children with a history of previous CHD surgery are more susceptible to infections, especially those infections with pulmonary involvements, as the lung involvement could cause worsening of the patient's condition by aggravating pulmonary hypertension. The results of the current study indicate that these patients are more prone to COVID-19 infection compared to the healthy children population.

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