A 10‐year‐old boy who was referred due to acute hydrocephalus symptoms was diagnosed as the first case of pediatric DLGNT in Iran. The results suggested that using shunting for hydrocephaly and ...anti‐seizure medicines, as well as chemotherapeutic agents, can be an effective treatment strategy for DLGNT. Although the patient was stable without a tumor recurrence for a limited follow‐up period of 22 months, further studies are expected.
A case of DLGNT was reported for the first time from Iran. Pediatric DLGNT may be successfully managed with shunting for hydrocephaly and anti‐seizure medicines, as well as chemotherapeutic agents. The patient did not have a tumor recurrence for a follow‐up period of 22 months.
Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder with varying symptomatology depending on the age of onset. The diagnosis of NP-C is challenging due to heterogeneous ...nonspecific clinical presentation of the disease. NP-C Suspicion Index (SI) was developed to aid screening and identification of patients with suspicion of NP-C for further clinical evaluation. Here we assess the performance of five NP-C SI models to identify patients with NP-C compared with clinical practice to determine the best SI model for identification of each clinical form of NP-C by age.
This was a post hoc analysis of a retrospective chart review of patient data collected from five expert NP-C centers. The study assessed the proportion of patients with NP-C who could have been identified using the Original SI, Refined SI, 2/7 SI, 2/3 SI, and Early-Onset SI and evaluated the performance of each SI against clinical practice. A score above a threshold of 70 points for the Original SI, 40 points for the Refined SI, 6 points for the Early-Onset SI, and 2 points for the 2/7 and 2/3 SIs represented identification of NP-C.
The study included 63 patients, and of these, 23.8% had a family history of NP-C. Of the available SI tools, the Refined SI performed well in identifying patients with NP-C across all age groups (77.8% infantile, 100% juvenile and 100% adult groups), and earlier identification than clinical diagnosis would have been possible in 50.0% of infantile, 72.7% of juvenile and 87.0% of adult patients. Patients who were not detected by the Refined SI prior to clinical diagnosis mainly presented with delayed developmental milestones, visceral manifestations, neurologic hypotonia, clumsiness, ataxia, vertical supranuclear gaze palsy, parent or siblings with NP-C, dysarthria/dysphagia and psychotic symptoms.
This study demonstrated the applicability of various SI models for screening and identification of patients with NP-C for further clinical evaluation. Although NP-C is rare and the patient population is limited, this study was conducted in a real-world setting and confirms SI models as useful screening tools that facilitate identification of patients with NP-C earlier in their disease course.
The occurrence of thiamine metabolism dysfunction syndrome (THMD), a rare autosomal recessive condition, may be linked to various mutations found in the TPK1 and SLC19A3 genes. The disease chiefly ...manifests through ataxia, muscle hypotonia, abrupt or subacute onset encephalopathy, and a decline in developmental milestones achieved during the early stages of infancy. We present findings from an investigation that involved two individuals from Iran, both of whom experienced seizures along with ataxia and hypotonia. The underlying genetic causes were found with the use of next-generation sequencing (NGS) technology, which has facilitated the detection of causal changes in a variety of genetic disorders.
The selection of cases for this study was based on the phenotypic and genetic information that was obtainable from the Center for Comprehensive Genetic Services. The genetic basis for the problems observed among the participants was determined through the application of whole-exome sequencing (WES). Subsequently, sanger sequencing was employed as a means of validating any identified variations suspected to be causative.
The first patient exhibited a homozygous mutation in the TPK1 gene, NM_022445.4:c.224 T > A:p.I75 N, resulting in the substitution of isoleucine for asparagine at position 75 (p.I75 N). In our investigation, patient 2 exhibited a homozygous variant, NM_025243.4:c.1385dupA:pY462X, within the SLC19A3 gene.
Collectively, when presented with patients showcasing ataxia, encephalopathy, and basal ganglia necrosis, it is essential to account for thiamine deficiency in light of the potential advantages of prompt intervention. At times, it may be feasible to rectify this deficiency through the timely administration of thiamine dosages. Accordingly, based on the results of the current investigation, these variations may be useful for the diagnosis and management of patients with THMD.
Background: Considering that better understanding of the underlying mechanisms and risk factors of arterial ischemic stroke (AIS) would be helpful for better management of stroke and its outcome in ...children as well as preventing or reducing the occurrence of its related potential disabilities, the aim of this study was to investigate the most common risk factors and causes of AIS in patients referred to the referral hospitals in Tehran and Isfahan cities of Iran. Methods: In this study, medical files of all pediatric patients admitted to the Mofid and Imam Hossein children's hospitals with the diagnosis of AIS from 2001 to 2011 and 2011 to 2016, respectively, were evaluated. Identified risk factors of AIS were categorized as arteriopathies, cardiac disorders (CDs), infection, acute head-and-neck disorders, acute systemic conditions, chronic systemic conditions, prothrombotic states, chronic head-and-neck disorders, atherosclerosis-related RFs, and others. Results: In this study, 61 patients were evaluated. Mean (standard deviation) age of the patients was 5.1 (3.9) years. About 62.3% of the patients were boys while 37.7% were girls (P < 0.01). A total of 36 patients (59%) had at least one risk factor for AIS. About 40.9% of patients had undetermined risk factors. CDs (21.31%) and vascular disease (21.31%) were the most common risk factors of AIS in the studied children. Nearly 11.5% of the patients had moyamoya vascular disease (MMD). Conclusion: The findings of our study indicated that the most common risk factors for AIS in the two studied regions are congenital heart and vascular diseases. The results of the current study could be used for planning more preventive strategies in patients suffering from the mentioned diseases. In addition, the obtained data could be used for conducting targeted education and management of high-risk patients.
Purpose: We aimed to present the ophthalmic manifestations of neuro-metabolic disorders.
Methods: Patients who were diagnosed with neuro-metabolic disorders in the Neurology Department of Mofid ...Pediatric Hospital in Tehran, Iran, between 2004 and 2014 were included in this study. Disorders were confirmed using clinical findings, neuroimaging, laboratory data, and genomic analyses. All enrolled patients were assessed for ophthalmological abnormalities.
Results: A total of 213 patients with 34 different neuro-metabolic disorders were included. Ophthalmological abnormalities were observed in 33.5% of patients. Abnormal findings in the anterior segment included Kayser-Fleischer rings, congenital or secondary cataracts, and lens dislocation into the anterior chamber. Posterior segment (i.e., retina, vitreous body, and optic nerve) evaluation revealed retinitis pigmentosa, cherry-red spots, and optic atrophy. In addition, strabismus, nystagmus, and lack of fixation were noted during external examination.
Conclusion: Ophthalmological examination and assessment is essential in patients that may exhibit neuro-metabolic disorders.
Next-generation sequencing (NGS) has been proven to be one of the most powerful diagnostic tools for rare Mendelian disorders. Several studies on the clinical application of NGS in unselected cohorts ...of Middle Eastern patients have reported a high diagnostic yield of up to 48%, correlated with a high level of consanguinity in these populations. We evaluated the diagnostic utility of NGS-based testing across different clinical indications in 1436 patients from Iran, representing the first study of its kind in this highly consanguineous population. A total of 1075 exome sequencing and 361 targeted gene panel sequencing were performed over 8 years at a single clinical genetics laboratory, with the majority of cases tested as proband-only (91.6%). The overall diagnostic rate was 46.7%, ranging from 24% in patients with an abnormality of prenatal development to over 67% in patients with an abnormality of the skin. We identified 660 pathogenic or likely pathogenic variants, including 241 novel variants, associated with over 342 known genetic conditions. The highly consanguineous nature of this cohort led to the diagnosis of autosomal recessive disorders in the majority of patients (79.1%) and allowed us to determine the shared carrier status of couples for suspected recessive phenotypes in their deceased child(ren) when direct testing was not possible. We also highlight the observations of recessive inheritance of genes previously associated only with dominant disorders and provide an expanded genotype-phenotype spectrum for multiple less-characterized genes. We present the largest mutational spectrum of known Mendelian disease, including possible founder variants, throughout the Iranian population, which can serve as a unique resource for clinical genomic studies locally and beyond.
Inborn errors of metabolism (IEM) are rare conditions, with an overall incidence of 1 per 1000 births. Approximately 40-60% of IEM cases present with epilepsy as one of the main clinical ...presentations of the disease. A substantial number of these patients require timely and accurate diagnosis, besides specific treatment to prevent the irreversible outcomes.
In this two-year retrospective study, a total of 128 patients with documented neurometabolic disorders were selected and evaluated in Mofid Children Hospital of Tehran, Iran, using a questionnaire to investigate the prevalence of epilepsy and seizure phenotypes. The collected data were evaluated in SPSS version 23.
Seizure was reported in 49% (63/128) of the patients. A single episode of seizure occurred in 7 (7%) patients. The prevalence of epilepsy was estimated at 42% (54/128). The most common seizure types were generalized tonic-clonic (43%), tonic (22%), and myoclonic (10%), respectively. Epilepsy was refractory in 30% (16/54) of the patients, and the mean number of administered anti-seizure drugs for refractory cases was 3.2. Overall, 50% of refractory cases had mixed-type seizures, and 25% had generalized tonic-clonic and myoclonic seizures.
Neurometabolic disorders are rare, but treatable causes of epilepsy. A considerable number of patients (42%) in the current study presented with epilepsy as a clinical feature of IEM.
Objective Neurometabolic disorders are an important group of diseases that mostly are presented in newborns and infants. Neurological manifestations are the prominent signs and symptoms in this group ...of diseases. Seizures are a common sign and are often refractory to antiepileptic drugs in untreated neurometabolic patients. The onset of symptoms for neurometabolic disorders appears after an interval of normal or near normal growth and development.Additionally, affected children may fare well until a catabolic crisis occurs. Patients with neurometabolic disorders during metabolic decompensation have severe clinical presentation, which include poor feeding, vomiting, lethargy, seizures, and loss of consciousness. This symptom is often fatal but severe neurological insult and regression in neurodevelopmental milestones can result as a prominent sign in patients who survived. Acute symptoms should be immediately treated regardless of the cause. A number of patients with neurometabolic disorders respond favorably and, in some instances, dramatically respond to treatment. Early detection and early intervention is invaluable in some patients to prevent catabolism and normal or near normal neurodevelopmental milestones. This paper discusses neurometabolic disorders, approaches to this group of diseases (from the view of a pediatric neurologist), clinical and neurological manifestations, neuroimaging and electroencephalography findings, early detection, and early treatment.
Epilepsy, in children, is a common neurological problem for referral to child neurology clinics. The prevalence of nonfebrile seizure in children (under 10 years old), is estimated from 5.2 to 8.1 ...per 1000. Also, the prevalence of epilepsy in Iran estimated about 5 %; it means 4 million people of Iranian population live with epilepsy in Iran. Although antiseizure drugs (ASDs) are the essential treatment modalities in most children, more than 30% of epileptic children have intractable seizures or they suffer from drug adverse effects secondary to these medications. Because only a limited number of epileptic patients benefit from surgical therapy using the additional therapeutic options is inevitable. There are many available nonpharmacologic proven therapies for refractory seizures that Dietary therapy ( Ketogenic Diet) is one of the important therapeutic options in this group. In this review, we will discuss the different features of pediatric epilepsy dietary therapies (Especially the Ketogenic Diet) in Iran and also the history of epilepsy in ancient Iran, utilization, effectiveness, side effects, tolerability, and acceptability as well as ongoing and future programs.
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