Neurologic Manifestations of Coronavirus Disease 2019 in Children: An Iranian Hospital-Based Study.

BACKGROUND: COVID-19 infection and its neurological manifestations were seen in children although less common than adults. The aim of this study was to determine the frequency of different types of neurologic findings of hospitalized children with COVID-19. ]. METHODS: This retrospective study was performed on hospitalized pediatric patients aged≤18 years with confirmed SARS-CoV-2 at Children's Medical Center Hospital. Neurological manifestations were defined as the presence of any of the following symptoms: seizure, altered mental status, behavioral/personality change, ataxia, stroke, muscle weakness, smell and taste dysfunctions, and focal neurological disorders. RESULTS: Fifty-four children with COVID-19 were admitted and their mean age was 6.94±4.06 years. Thirty-four of them (63%) were male. The most frequent neurological manifestation was seizure (19 [45%]) followed by muscle weakness (11 [26%]), loss of consciousness (10 [23%]), and focal neurological disorders (10 [23%]). Other neurological manifestations consisted of headache (n=7), movement disorders (n=6), behavioral/personality change (n=5), ataxia (n=3), and stroke (n=3). Twenty-nine percent of our patients had leukocytosis. A neutrophil count above 70% was seen in 31% of participants. Among our patients, 81% had a positive reverse-transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2. CONCLUSION: During the current pandemic outbreak, hospitalized children with COVID-19 should be evaluated for neurological signs because it is common among them and should not be under-estimated.

Expanding the neuroimaging findings of guanidinoacetate methyltransferase deficiency in an Iranian girl with a homozygous frameshift variant in the GAMT.

Guanidinoacetate methyltransferase deficiency (GAMTD) is a treatable neurodevelopmental disorder with normal or nonspecific imaging findings. Here, we reported a 14-month-old girl with GAMTD and novel findings on brain magnetic resonance imaging (MRI).A 14-||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||month-old female patient was referred to Myelin Disorders Clinic due to onset of seizures and developmental regression following routine vaccination at 4 months of age. Brain MRI, prior to initiation of treatment, showed high signal intensity in T2-weighted imaging in bilateral thalami, globus pallidus, subthalamic nuclei, substantia nigra, dentate nuclei, central tegmental tracts in the brainstem, and posterior periventricular white matter which was masquerading for mitochondrial leukodystrophy. Basic metabolic tests were normal except for low urine creatinine; however, exome sequencing identified a homozygous frameshift deletion variant [NM_000156: c.491del; (p.Gly164AlafsTer14)] in the GAMT. Biallelic pathogenic or likely pathogenic variants cause GAMTD. We confirmed the homozygous state for this variant in the proband, as well as the heterozygote state in the parents by Sanger sequencing.MRI features in GAMTD can mimic mitochondrial leukodystrophy. Pediatric neurologists should be aware of variable MRI findings in GAMTD since they would be misleading to other diagnoses.

The quality of life in children with spinal muscular atrophy: a case-control study.

OBJECTIVES: This study aimed to analyze the health-related quality of life (HRQoL) of patients with spinal muscular atrophy (SMA) based on the type of SMA, demographic and clinical features and compare HRQoL of these patients with a matched healthy control group.  METHODS: This was a case-control study of Patients with SMA in Iran. Sixty-six patients with SMA type II and III aged 8-18 years and also 264 healthy age, sex, and socio-economic matched individuals were enrolled. To assess the quality of life, we used the Persian version of the KIDSCREEN-27. RESULTS: The health-related quality of life between children with type II and type III SMA was not significant in all 5 subscales. However, HRQoL in healthy children was significantly higher than in SMA children in all 5 subscales. CONCLUSION: The quality of life in children with SMA was lower than the healthy control group in all subscales, and physical well-being and psychosocial aspects are the main domains of life impaired by SMA disease. However, no significant difference between the quality of life in children with SMA type II and type III was observed.

Childhood Guillain-Barre syndrome in the SARS-CoV-2 era: Is there any causative relation?

We reported an association between SARS-CoV-2 infection and Guillain-Barre syndrome (GBS). From 37 patients with GBS, previous SARS-CoV-2 clinical clues, including fever, cough, and diarrhea, were recorded in 18 patients. Among them, SARS-CoV-2 IgG was detected in seven patients, considered confirmed as cases. SARS-CoV-2 PCR was positive in just one patient. Although we found no increase in patient recruitment during the pandemic compared to previous years, our study indicated that SARS-CoV-2 is associated with poorer outcomes regarding GBS disability scale and hospital stay.

Follow-up of 25 patients with treatable ataxia: A comprehensive case series study.

Autosomal recessive cerebellar ataxias are a group of heterogeneous early-onset progressive disorders that some of them are treatable. We performed a 4-year follow-up for 25 patients who had treatable ataxia. According to our study, patients would benefit from early detection of treatable ataxia, close observation, and follow-up.

Epilepsia Partialis Continua a Clinical Feature of a Missense Variant in the ADCK3 Gene and Poor Response to Therapy.

INTRODUCTION: Coenzyme Q10 deficiency can be due to mutations in Coenzyme Q10-biosynthesis genes (primary) or genes unrelated to biosynthesis (secondary). Primary Coenzyme Q10 deficiency-4 (COQ10D4), also known as autosomal recessive spinocerebellar ataxia-9 (SCAR9), is an autosomal recessive disorder caused by mutations in the ADCK3 gene. This disorder is characterized by several clinical manifestations such as severe infantile multisystemic illness, encephalomyopathy, isolated myopathy, cerebellar ataxia, or nephrotic syndrome. METHODS: In this study, whole-exome sequencing was performed in order to identify disease-causing variants in an affected girl with developmental regression and Epilepsia Partialis Continua (EPC). Next, Sanger sequencing method was used to confirm the identified variant in the patient and segregation analysis in her parents. CASE PRESENTATION: The proband is an affected 11-year-old girl with persistent seizures, EPC, and developmental regression including motor, cognition, and speech. Seizures were not controlled with various anticonvulsant drugs despite adequate dosing. Progressive cerebellar atrophy, stroke-like cortical involvement, multifocal hyperintense bright objects, and restriction in diffusion-weighted imaging (DWI) were seen in the brain magnetic resonance imaging (MRI). CONCLUSIONS: A novel homozygous missense variant [NM_020247.5: c.814G>T; (p.Gly272Cys)] was identified within the ADCK3 gene, which is the first mutation in this gene in the Iranian population. Bioinformatics analysis showed this variant is damaging. Based on our patient, clinicians should consider genetic testing earlier to instant diagnosis and satisfactory treatment based on exact etiology to prevent further neurologic sequelae.

Genetic Analysis of Forty MLPA-Negative Duchenne Muscular Dystrophy Patients by Whole-Exome Sequencing.

This manuscript aimed to determine the underlying point mutations causing Duchenne muscular dystrophy (DMD) in a heterogeneous group of Iranian patients, who are clinically suspected. Whole-exome sequencing was utilized to detect disease-causing variants in 40 MLPA-negative DMD patients. Disease-causing variants were detected in the DMD gene in 36/40 of the patients (90%), and 4/40 of them (10%) remained undiagnosed. WES analysis revealed that nonsense variant was the most common type in our study (23/36 of the cases). Besides, 12/36 of the cases had frameshift variant, and one of the patients had a likely pathogenic splice variant in the DMD gene. Carrier testing revealed that 21/40 of the mothers had the identified variant. Therefore, most variants were inherited (58.3%), while 19/40 were de novo (41. 7%). The present study has demonstrated the importance of performing WES to detect disease-causing point mutations in MLPA-negative DMD patients and to identify carrier females. Due to regulatory challenges, the clinical development of therapeutic approaches is time-consuming and may not be available to all patients shortly. Therefore, it appears that the techniques used to accurately detect disease-causing variants in carrier mothers are a more efficient solution to prevent the increased prevalence of DMD.

Primary and Secondary Microcephaly, Global Developmental Delay, and Seizure in Two Siblings Caused by a Novel Missense Variant in the ZNF335 Gene.

Autosomal recessive microcephaly is a rare clinical condition, which is characterized by reduced brain size that can be associated with delayed intellectual ability, developmental delay, and seizure. In this study, we describe two siblings with microcephaly: a 12-year-old girl with primary microcephaly, and a 7-year-old boy with secondary microcephaly, whose episodes of seizure and neurodevelopmental regression started at 6 years and 6 months of age, respectively. The interesting finding in these siblings was two different presentations of the same variant: one case with primary and one case with secondary microcephaly. Whole-exome sequencing was performed in order to identify causative variants in one family having two affected siblings with microcephaly. Confirmation of the identified variant in the ZNF335 gene in the proband and her affected brother and segregation analysis in the family were performed using the Sanger sequencing method. In both patients, a novel homozygous missense variant, [NM_022095.4: c.3346G>A; p.(Gly1116Arg)], in the ZNF335 gene was identified. The p.(Gly1116Arg) variant causes a defect in the last zinc finger domain of the protein. Conservation analysis by ConSurf server and UCSC genome browser revealed that Gly1116 is a highly conserved amino acid among different species. Different in-silico prediction tools and bioinformatics analysis predicted this variant as damaging.

A flowering inhibitor of the temperature-dependent pathway in Crocus sativus L.

Saffron is the world highest-priced spice because its production requires intensive hand labour. Reduce saffron production costs require containerised plant production under controlled conditions and expand the flowering period. Controlling the flowering process and identify the factors involved in saffron flowering is crucial to introduce technical improvements. The research carried out so far in saffron has allowed an extensive knowledge of the influence of temperature on the flower induction, but the molecular mechanisms controlling flowering induction processes are largely unknown. The present study is the first conducted to isolate and characterize a regulator gene of saffron floral induction the Short Vegetative Phase (SVP) gene, which represses the floral initiation genes in the temperature response pathway, which involved in saffron flower induction. The results obtained from both phylogenetic analysis and T-coffee alignment confirms that the isolated sequence belongs to the SVP gene clades of MADS-box gene family. Gene expression analysis in different developmental stages revealed the highest expression of SVP transcript (CsSVP) during the dormancy and the vegetative stages, but decrease when flower development initiated and it was the least in late September when flower primordia are developed. Furthermore, its expression increased in the apical bud when corms are storage at 9-10 ºC, thus inhibiting flower induction. Additionally, comparison of the CsSVP transcript in apical buds from big and small corms, differing in their flowering capacity, indicates that the CsSVP transcript is present only in vegetative buds. Taken together, these results suggested inhibitory role of the SVP gene.