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Introduction: Diencephalic-mesencephalic junction dysplasia syndrome is a rare neurogenetic disorder reported to be caused by variants in several genes. Phenotypic presentation is characterized by clinical findings including developmental delay, hypotonia, spasticity, and dyskinetic movements in combination with distinctive imaging features on brain magnetic resonance imaging (MRI). Methods: Whole exome sequencing was conducted to unveil the molecular etiology of patients presenting with neurological manifestations from two unrelated families. Results: To the best of our knowledge, here we report the third family affected with diencephalic-mesencephalic junction dysplasia caused by a novel variant in GSX2 and two siblings with a PCDH12 variant exhibiting a less severe phenotype. The siblings with a PCDH12 variant were positioned at the milder end of the phenotypic spectrum. Although both exhibited a clinical phenotype resembling cerebral palsy, one showed partial fusion of the hypothalamus and mesencephalon, whereas MRI was unremarkable in the other. Biallelic GSX2 variants have been implicated in basal ganglia agenesis, and similarly, our patients had basal ganglia hypoplasia along with hypothalamic-mesencephalic fusion. Conclusion: Identifying variants associated with the syndrome in different genes will contribute to genotype-phenotype correlation.
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OBJECTIVE: Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, autosomal recessive disorder resulting from axonal midline crossing defect due to variants in ROBO3. METHODS: We retrospectively evaluated demographics, clinical phenotype, course of spinal deformities, and neuroimaging findings of six Turkish patients with HGPPS. We performed targeted gene testing by next-generation sequencing. RESULTS: The median age at symptom onset and diagnosis was 1.5 years (0.5-4), and 11 years (2-16), respectively. Oculomotor signs were the most common presenting symptom (n = 4), followed by scoliosis (n = 2). The course of scoliosis was progressive and accompanied by kyphosis, showed intrafamilial variability, and was corrected surgically in three of the patients. Intellectual disability (n = 4), hypergonadotropic hypogonadism (n = 2), hearing loss (n = 2), and tranisent movement disorders (n = 1) were additional features. Targeted gene sequencing revealed five distinct homozygous variants. Of the four novel variants, two of them were located in the acceptor site of the noncoding region of the gene, remaining two were missense and frameshift variants, located in immunoglobulin-like domain-2, and cytoplasmic signaling motif 2, respectively. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) showed the absence of decussation of superior cerebellar peduncle and dorsal transverse pontine fibers. INTERPRETATION: Spectrum of HGPPS is further expanded with novel variants in the ROBO3 with clinical and radiological fingerprints. Spinal deformities require close orthopedic screening and individualized approach. Intellectual disability and hearing loss emerge as additional features. Hypogonadism and transient subtle movement disorders require further attention and confirmation from other series.
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Receptores de Superfície Celular , Escoliose , Humanos , Escoliose/genética , Escoliose/diagnóstico por imagem , Masculino , Feminino , Criança , Adolescente , Pré-Escolar , Estudos Retrospectivos , Receptores de Superfície Celular/genética , Oftalmoplegia Externa Progressiva Crônica/genética , Receptores Imunológicos/genética , Lactente , Fenótipo , Transtornos Congênitos de Denervação Craniana , Proteínas RoundaboutRESUMO
BACKGROUND: Complex spinal deformities necessitate surgical interventions that may intervene with intrathecal injections in patients with spinal muscular atrophy (SMA). This study aimed to determine the effect of spinal deformity correction surgery on nusinersen administration. METHODS: Pediatric patients with SMA, operated by a single surgeon, either via magnetically controlled growing rod (MCGR) or definitive fusion (DF) with skip instrumentation, were evaluated retrospectively in terms of safety and feasibility of intrathecal injections. Patients' and their parents' perspectives were evaluated through a questionnaire regarding any shift in the setting of injections. RESULTS: Fourteen patients with 15 spinal surgeries (10 MCGR and 5 DF) were included. Eleven patients received intrathecal treatment both before and after the surgery. Preoperative (n=3) and postoperative (n=9) fluoroscopic guidance was required leading to a shift in the application settings in 6 patients. Of 106 preoperative injections, 15% required fluoroscopy and 2% required anesthesia. Postoperatively, of 88 injections, 73% required fluoroscopy and 26% required anesthesia. No patients discontinued intrathecal injections due to technical difficulties associated with the spinal surgery. CONCLUSIONS: This study demonstrates that spinal surgery does not prevent safe and successful intrathecal nusinersen injections. In the DF group, the skip instrumentation technique provided access to interlaminal space for intrathecal injections. In either surgical group, no further auxillary approach was required. Modifications in the injection technique require an institutional approach, and concerns of patients and their families should be addressed accordingly. LEVEL OF EVIDENCE: IV.
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Injeções Espinhais , Oligonucleotídeos , Fusão Vertebral , Humanos , Oligonucleotídeos/administração & dosagem , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , Criança , Fusão Vertebral/métodos , Lactente , Fluoroscopia , Atrofias Musculares Espinais da Infância/tratamento farmacológico , Atrofias Musculares Espinais da Infância/cirurgia , Resultado do Tratamento , Atrofia Muscular Espinal/tratamento farmacológico , Atrofia Muscular Espinal/cirurgia , Estudos de ViabilidadeRESUMO
Anti-Ku autoantibodies are associated with several autoimmune inflammatory diseases. We aimed to review our anti-Ku positive pediatric patients in this study. Four pediatric patients (all female) who had anti-Ku positivity were included (Patients 1-2-3 with idiopathic inflammatory myopathy (IIM); Patient 4 with chronic urticaria). Patient 1 (onset:10.5 years) had proximal muscle weakness, Raynaud phenomenon, sclerodactyly, hyperpigmentation, joint contracture, and tenosynovitis. The disease course was progressive despite treatment with corticosteroids, intravenous immunoglobulin (IVIG), plasma exchange, and 11 different immunosuppressive drugs. Patient 2 (onset:15 years) presented with proximal muscle weakness, fatigue, weight loss. She recovered normal muscle strength after treatment with corticosteroids, IVIG, methotrexate, cyclosporine A, mycophenolate mofetil. Patient 3 (onset:10 years) had juvenile dermatomyositis with proximal muscle weakness, Gottron's papules, and calcinosis. She also had anti-NXP2 positivity. Remission was achieved with corticosteroids, methotrexate, azathioprine, and infliximab. Muscle biopsy findings revealed a variable spectrum of necrosis, regeneration, perifascicular pattern, and inflammation. Patient 4 had only chronic urticaria (onset: 6.5 years). The striking features of this series were heterogeneity in clinical presentations including solely chronic urticaria and IIM; variable response to immunosuppressive treatments; and histopathology revealing a spectrum of necrosis, regeneration and inflammatory infiltration. Expanding the spectrum of anti-Ku positivity will allow better understanding of anti-Ku-associated phenotype clusters.
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Autoanticorpos , Autoantígeno Ku , Fenótipo , Humanos , Feminino , Adolescente , Criança , Autoantígeno Ku/imunologia , Autoanticorpos/sangue , Miosite/imunologia , Miosite/tratamento farmacológico , Urticária Crônica/tratamento farmacológico , Urticária Crônica/imunologiaRESUMO
Collagen VI-related dystrophies (COL6-RDs) manifest with a spectrum of clinical phenotypes, ranging from Ullrich congenital muscular dystrophy (UCMD), presenting with prominent congenital symptoms and characterised by progressive muscle weakness, joint contractures and respiratory insufficiency, to Bethlem muscular dystrophy, with milder symptoms typically recognised later and at times resembling a limb girdle muscular dystrophy, and intermediate phenotypes falling between UCMD and Bethlem muscular dystrophy. Despite clinical and immunohistochemical features highly suggestive of COL6-RD, some patients had remained without an identified causative variant in COL6A1, COL6A2 or COL6A3. With combined muscle RNA-sequencing and whole-genome sequencing we uncovered a recurrent, de novo deep intronic variant in intron 11 of COL6A1 (c.930+189C>T) that leads to a dominantly acting in-frame pseudoexon insertion. We subsequently identified and have characterised an international cohort of forty-four patients with this COL6A1 intron 11 causative variant, one of the most common recurrent causative variants in the collagen VI genes. Patients manifest a consistently severe phenotype characterised by a paucity of early symptoms followed by an accelerated progression to a severe form of UCMD, except for one patient with somatic mosaicism for this COL6A1 intron 11 variant who manifests a milder phenotype consistent with Bethlem muscular dystrophy. Characterisation of this individual provides a robust validation for the development of our pseudoexon skipping therapy. We have previously shown that splice-modulating antisense oligomers applied in vitro effectively decreased the abundance of the mutant pseudoexon-containing COL6A1 transcripts to levels comparable to the in vivo scenario of the somatic mosaicism shown here, indicating that this therapeutic approach carries significant translational promise for ameliorating the severe form of UCMD caused by this common recurrent COL6A1 causative variant to a Bethlem muscular dystrophy phenotype.
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OBJECTIVE: The aim of the study is to evaluate predictors of clinically important neuroimaging results, that is, computed tomography and magnetic resonance imaging in children in an academic pediatric emergency department (PED) from 2015 to 2019. METHODS: This study was conducted in an academic PED. The patient's demographic and clinical characteristics of PED visits and neuroimaging findings requested at the PED were recorded for January 1, 2015, to December 31, 2019. In addition, descriptive statistics and logistic regression analyses were conducted. We described and determined the predictors of clinically important neuroimaging findings in children. RESULTS: Clinically important neuroimaging findings were detected in patients with blurred vision ( P = 0.001), ataxia ( P = 0.003), unilateral weakness ( P = 0.004), and altered level of consciousness ( P = 0.026). Clinically important neuroimaging was found 9.4 times higher in patients with altered level of consciousness, 7.4 times higher in patients with focal weakness, 4.6 times higher in patients with blurred vision, and 3.5 times more in patients presenting with ataxia. CONCLUSIONS: Advanced neuroimaging, especially for selected patients in PED, can improve the quality of health care for patients. On the other hand, irrelevant neuroimaging findings can lead physicians away from prompt diagnosis and accurate management. According to our study, advanced neuroimaging can be performed in the early period for both diagnosis and early treatment, especially in selected patients with ataxia, blurred vision, altered consciousness, and unilateral weakness. In other cases, clinicians may find more supporting evidence.
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Serviço Hospitalar de Emergência , Imageamento por Ressonância Magnética , Neuroimagem , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Criança , Neuroimagem/métodos , Pré-Escolar , Adolescente , Lactente , Estudos Retrospectivos , AtaxiaRESUMO
Spinal muscular atrophy (SMA) is a genetic disorder that causes progressive degeneration of lower motor neurons and the subsequent loss of muscle function throughout the body. It is the second most common recessive disorder in individuals of European descent and is present in all populations. Accurate tools exist for diagnosing SMA from genome sequencing data. However, there are no publicly available tools for GRCh38-aligned data from panel or exome sequencing assays which continue to be used as first line tests for neuromuscular disorders. This deficiency creates a critical gap in our ability to diagnose SMA in large existing rare disease cohorts, as well as newly sequenced exome and panel datasets. We therefore developed and extensively validated a new tool - SMA Finder - that can diagnose SMA not only in genome, but also exome and panel sequencing samples aligned to GRCh37, GRCh38, or T2T-CHM13. It works by evaluating aligned reads that overlap the c.840 position of SMN1 and SMN2 in order to detect the most common molecular causes of SMA. We applied SMA Finder to 16,626 exomes and 3,911 genomes from heterogeneous rare disease cohorts sequenced at the Broad Institute Center for Mendelian Genomics as well as 1,157 exomes and 8,762 panel sequencing samples from Tartu University Hospital. SMA Finder correctly identified all 16 known SMA cases and reported nine novel diagnoses which have since been confirmed by clinical testing, with another four novel diagnoses undergoing validation. Notably, out of the 29 total SMA positive cases, 23 had an initial clinical diagnosis of muscular dystrophy, congenital myasthenic syndrome, or myopathy. This underscored the frequency with which SMA can be misdiagnosed as other neuromuscular disorders and confirmed the utility of using SMA Finder to reanalyze phenotypically diverse neuromuscular disease cohorts. Finally, we evaluated SMA Finder on 198,868 individuals that had both exome and genome sequencing data within the UK Biobank (UKBB) and found that SMA Finder's overall false positive rate was less than 1 / 200,000 exome samples, and its positive predictive value (PPV) was 97%. We also observed 100% concordance between UKBB exome and genome calls. This analysis showed that, even though it is located within a segmental duplication, the most common causal variant for SMA can be detected with comparable accuracy to monogenic disease variants in non-repetitive regions. Additionally, the high PPV demonstrated by SMA Finder, the existence of treatment options for SMA in which early diagnosis is imperative for therapeutic benefit, as well as widespread availability of clinical confirmatory testing for SMA, warrants the addition of SMN1 to the ACMG list of genes with reportable secondary findings after genome and exome sequencing.
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OBJECTIVE: To evaluate clinical characteristics and long-term outcomes in patients with guanidinoacetate methyltransferase (GAMT) deficiency with a special emphasis on seizures and electroencephalography (EEG) findings. METHODS: We retrospectively analyzed the clinical and molecular characteristics, seizure types, EEG findings, neuroimaging features, clinical severity scores, and treatment outcomes in six patients diagnosed with GAMT deficiency. RESULTS: Median age at presentation and diagnosis were 11.5 months (8-12 months) and 63 months (18 months -11 years), respectively. Median duration of follow-up was 14 years. Global developmental delay (6/6) and seizures (5/6) were the most common symptoms. Four patients presented with febrile seizures. The age at seizure-onset ranged between 8 months and 4 years. Most common seizure types were generalized tonic seizures (n = 4) and motor seizures resulting in drop attacks (n = 3). Slow background activity (n = 5) and generalized irregular sharp and slow waves (n = 3) were the most common EEG findings. Burst-suppression and electrical status epilepticus during slow-wave sleep (ESES) pattern was present in one patient. Three of six patients had drug-resistant epilepsy. Post-treatment clinical severity scores showed improvement regarding movement disorders and epilepsy. All patients were seizure-free in the follow-up. CONCLUSIONS: Epilepsy is one of the main symptoms in GAMT deficiency with various seizure types and non-specific EEG findings. Early diagnosis and initiation of treatment are crucial for better seizure and cognitive outcomes. This long-term follow up study highlights to include cerebral creatine deficiency syndromes in the differential diagnosis of patients with global developmental delay and epilepsy and describes the course under treatment.
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Eletroencefalografia , Guanidinoacetato N-Metiltransferase/deficiência , Transtornos do Desenvolvimento da Linguagem , Transtornos dos Movimentos/congênito , Humanos , Masculino , Feminino , Pré-Escolar , Lactente , Criança , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/fisiopatologia , Convulsões/etiologia , Convulsões/tratamento farmacológico , Transtornos dos Movimentos/diagnóstico , Seguimentos , Deficiências do Desenvolvimento/etiologiaRESUMO
ADPRHL2 is involved in posttranslational modification and is known to have a role in physiological functions such as cell signaling, DNA repair, gene control, cell death, and response to stress. Recently, a group of neurological disorders due to ADPRHL2 variants is described, characterized by childhood-onset, stress-induced variable movement disorders, neuropathy, seizures, and neurodegenerative course. We present the diagnostic pathway of two pediatric patients with episodic dystonia and ataxia, who later had a neurodegenerative course complicated by central hypoventilation syndrome due to the same homozygous ADPRHL2 variant. We conducted a systematic literature search and data extraction procedure following the Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 statement in terms of patients with ADPRHL2 variants, from 2018 up to 3 February, 2023. In total, 12 articles describing 47 patients were included in the final analysis. Median age at symptom onset was 2 (0.7-25) years, with the most common presenting symptoms being gait problems (n = 19, 40.4%), seizures (n = 16, 34%), ataxia (n = 13, 27.6%), and weakness (n = 10, 21.2%). Triggering factors (28/47; 59.5%) and regression (28/43; 60.4%), axonal polyneuropathy (9/23; 39.1%), and cerebral and cerebellar atrophy with white matter changes (28/36; 77.7%) were the other clues. The fatality rate and median age of death were 44.6% (n = 21) and 7 (2-34) years, respectively. ADPRHL2 variants should be considered in the context of episodic, stress-induced pediatric and adult-onset movement disorders and seizures.
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Ataxia , Humanos , Masculino , Criança , Feminino , Pré-Escolar , Adolescente , Adulto Jovem , Ataxia/genética , Ataxia/fisiopatologia , Adulto , Lactente , Hipoventilação/genética , Hipoventilação/diagnósticoRESUMO
OBJECTIVES: The MetabQoL 1.0 is the first disease-specific health related quality of life (HrQoL) questionnaire for patients with intoxication-type inherited metabolic disorders. Our aim was to assess the validity and reliability of the MetabQoL 1.0, and to investigate neuropsychiatric burden in our patient population. METHODS: Data from 29 patients followed at a single center, aged between 8 and 18 years with the diagnosis of methylmalonic acidemia (MMA), propionic acidemia (PA) or isovaleric acidemia (IVA), and their parents were included. The Pediatric Quality of Life Inventory (PedsQoL) was used to evaluate the validity and reliability of MetabQoL 1.0. RESULTS: The MetabQoL 1.0 was shown to be valid and reliable (Cronbach's alpha: 0.64-0.9). Fourteen out of the 22 patients (63.6%) formally evaluated had neurological findings. Of note, 17 out of 20 patients (85%) had a psychiatric disorder when evaluated formally by a child and adolescent psychiatrist. The median mental scores of the MetabQoL 1.0 proxy report were significantly higher than those of the self report (p = 0.023). Patients with neonatal-onset disease had higher MetabQoL 1.0 proxy physical (p = 0.008), mental (p = 0.042), total scores (p = 0.022); and self report social (p = 0.007) and total scores (p = 0.043) than those with later onset disease. CONCLUSIONS: This study continues to prove that the MetabQoL 1.0 is an effective tool to measure what matters in intoxication-type inherited metabolic disorders. Our results highlight the importance of clinical assessment complemented by patient reported outcomes which further expands the evaluation toolbox of inherited metabolic diseases.
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Erros Inatos do Metabolismo dos Aminoácidos , Acidemia Propiônica , Criança , Recém-Nascido , Adolescente , Humanos , Acidemia Propiônica/diagnóstico , Qualidade de Vida/psicologia , Turquia , Reprodutibilidade dos Testes , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Inquéritos e QuestionáriosRESUMO
In a currently 13-year-old girl of consanguineous Turkish parents, who developed unsteady gait and polyneuropathy at the ages of 3 and 6 years, respectively, we performed whole genome sequencing and identified a biallelic missense variant c.424C>T, p.R142W in glypican 1 (GPC1) as a putative disease-associated variant. Up to date, GPC1 has not been associated with a neuromuscular disorder, and we hypothesized that this variant, predicted as deleterious, may be causative for the disease. Using mass spectrometry-based proteomics, we investigated the interactome of GPC1 WT and the missense variant. We identified 198 proteins interacting with GPC1, of which 16 were altered for the missense variant. This included CANX as well as vacuolar ATPase (V-ATPase) and the mammalian target of rapamycin complex 1 (mTORC1) complex members, whose dysregulation could have a potential impact on disease severity in the patient. Importantly, these proteins are novel interaction partners of GPC1. At 10.5 years, the patient developed dilated cardiomyopathy and kyphoscoliosis, and Friedreich's ataxia (FRDA) was suspected. Given the unusually severe phenotype in a patient with FRDA carrying only 104 biallelic GAA repeat expansions in FXN, we currently speculate that disturbed GPC1 function may have exacerbated the disease phenotype. LC-MS/MS data are accessible in the ProteomeXchange Consortium (PXD040023).
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Ataxia de Friedreich , Proteômica , Humanos , Ataxia , Cromatografia Líquida , Ataxia de Friedreich/genética , Ataxia de Friedreich/metabolismo , Glipicanas/metabolismo , Proteínas de Ligação ao Ferro/genética , Proteínas de Ligação ao Ferro/metabolismo , Espectrometria de Massas em Tandem , Feminino , AdolescenteRESUMO
BACKGROUND: Management of pediatric patients presenting with first seizure is challenging, especially with regards to emergent neuroimaging. The rate of abnormal neuroimaging findings is known to be higher in focal seizures than in generalized seizures, but those intracranial abnormalities are not always clinically emergent. In this study, we aimed to determine the rate and indicators for clinically important intracranial abnormalities that change acute management in children presenting with a first focal seizure to the pediatric emergency department (PED). METHODS: This study was conducted retrospectively in the PED at a University Children`s Hospital setting. The study population consisted of patients aged between 30 days and 18 years with first focal seizure and who had emergent neuroimaging at the PED between the years 2001 and 2012. RESULTS: There were 65 eligible patients meeting the study criteria. Clinically important intracranial abnormalities requiring emergent neurosurgical or medical intervention were detected in 18 patients (27.7%) at the PED. Four patients (6.1%) underwent emergent surgical procedures. Seizure recurrence and the need for acute seizure treatment in the PED were significantly associated with clinically important intracranial abnormalities. CONCLUSIONS: Neuroimaging study yielding of 27.7% shows that first focal seizure must be evaluated meticulously. From the emergency department`s point of view; we suggest that first focal seizures in children should be evaluated with emergent neuroimaging, if possible with magnetic resonance imaging. Especially patients with recurrent seizures at presentation requires more careful evaluation.
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Serviço Hospitalar de Emergência , Convulsões , Humanos , Criança , Lactente , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Convulsões/etiologia , Hospitais Universitários , NeuroimagemRESUMO
BACKGROUND/OBJECTIVE: Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myopathy is rare in children. Here, we present a boy with relapsing refractory anti-HMGCR myopathy along with a systematic literature review. CASE REPORT: 17-year-old boy with five years of muscle weakness, rash, high creatinine kinase (CK) levels, and muscle biopsy compatible with inflammatory myopathy was diagnosed with juvenile dermatomyositis. He was treated with corticosteroids, intravenous immunoglobulin (IVIG), and methotrexate. His muscle weakness improved with this treatment although never completely resolved. CK levels decreased from â¼15000 U/L to â¼3000 U/L. At the age of 15, muscle weakness relapsed after an upper respiratory tract infection; pulse corticosteroid treatment was administered. The re-evaluated muscle biopsy showed a necrotizing pattern and the HMGCR antibody was positive confirming anti-HMGCR myopathy when he was 16. The diagnostic delay was 50 months. Disease activity was monitored by Medical Research Council score, MRI and functional tests. Despite corticosteroids, methotrexate, IVIG, cyclosporine A, and rituximab therapies, muscle weakness improved only slightly during the first three months and remained stable afterwards.Results of the Literature Search:We identified 16 articles describing 50 children (76% female) with anti-HMGCR myopathy by reviewing the English literature up to March 1st, 2022. Proximal muscle weakness was the most common clinical symptom (70.8%). Corticosteroids (84.8%), IVIG (58.7%), and methotrexate (56.5%) were preferred in most cases. Complete remission was achieved in nine patients (28.1%). CONCLUSION: Diagnosis and management of children with anti-HMGCR myopathy are challenging. Complete remission is achieved in only one third of these patients. Imaging biomarkers may aid treatment.
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Doenças Musculares , Oxirredutases , Masculino , Humanos , Criança , Feminino , Adolescente , Oxirredutases/uso terapêutico , Coenzima A/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Metotrexato/uso terapêutico , Diagnóstico Tardio , Autoanticorpos , Doenças Musculares/patologia , Debilidade MuscularRESUMO
BACKGROUND/OBJECTIVES: The aim of our study is twofold: To evaluate the presentation, diagnosis, clinical course, and management of juvenile dermatomyositis (JDM) in children under three years of age, and to compare with older-onset patients. METHODS: Nine patients with early-onset, and 63 patients with older-onset JDM followed between December 2010 and April 2022 are included. We also reviewed the literature on early-onset JDM from the inceptions of the PubMed/MEDLINE and Scopus databases up to April 1st, 2022. RESULTS: Early-onset JDM patients were characterized by longer median diagnostic delay (p = 0.005), calcinosis (p = 0.006), anti-NXP2 antibody (p = 0.049). Diagnostic pathway included muscle biopsy (77.7% versus 50.8%). Muscle biopsy findings were more severe in the early-onset group (p<0.001). Although there was no difference in the partial and complete remission rates, the relapse rate was significantly higher in the early-onset group (p = 0.001), reflected to requirement of intravenous immunoglobulin (p = 0.001), cyclophosphamide (p = 0.011), and biological agents (p = 0.016). Literature search revealed 32 articles reporting 75 patients. The median diagnostic delay was 5 (1-30) months. Calcinosis was present in 29.5%. Twenty-three of the 44 patients (52.3%) had a muscle biopsy. Forty-one patients (64.1%) received second and third-line treatments. Complete remission was achieved in almost half of these patients (48.9%), but relapse was observed in 75%. The mortality rate was 10.2%. CONCLUSION: Diagnosis can be challenging and delayed in early-onset JDM patients. Compared to older-onset JDM patients, this group had higher relapse rate, more severe muscle biopsy findings, and received intensive immunosuppressive treatment.
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Calcinose , Dermatomiosite , Criança , Humanos , Pré-Escolar , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Centros de Atenção Terciária , Diagnóstico Tardio , Estudos Retrospectivos , Calcinose/diagnósticoRESUMO
LPIN1 deficiency is an autosomal recessive disease caused by biallelic mutations in LPIN1, where impaired fatty acid metabolism leads to stress in skeletal muscle, resulting in severe rhabdomyolysis, often triggered by fever, exercise, fasting, and anesthesia. It is the second most common cause of severe, recurrent episodes of rhabdomyolysis in early childhood which can result in serious morbidity and mortality. To date, 71 patients have been published in 20 clinical studies in the form of case series. We describe two previously unreported cases, one with a novel LPIN1 mutation that resulted in mortality, and another, to the best of our knowledge, with the first reported compartment syndrome managed with a favorable outcome in this disorder. Recognition of the complications including ventricular arrythmias, acute renal failure and compartment syndrome on the severe end of the spectrum may change the outcome and prognosis of this devastating condition.
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Síndromes Compartimentais , Rabdomiólise , Humanos , Pré-Escolar , Fosfatidato Fosfatase/genética , Mutação , Rabdomiólise/etiologia , Músculo Esquelético/metabolismo , Síndromes Compartimentais/complicações , Síndromes Compartimentais/metabolismoRESUMO
The term 'neuromuscular diseases' defines disorders of the extended motor unit. Newborns with disorders of peripheral nervous system (PNS) (motor neurons, nerve roots, plexuses, peripheral nerves, neuromuscular junction, and skeletal muscles) present most frequently with hypotonia, weakness, contractures, respiratory and feeding difficulties. Challenge in the newborn period is, hypotonia may also occur with more common central causes such as; electrolyte disturbances, sepsis, hypoxic-ischemic encephalopathy (HIE), congestive heart failure, and inborn errors of metabolism. Moreover, newborns with PNS involvement and/or genetic neuromuscular disorders (NMD) can also be prone to intrapartum asphyxia which further masks an underlying condition. This is why, NMD is also described as one of the 'HIE-mimics'. Genetic counseling, individualized treatment strategies, standards of care require accurate diagnosis. Neuromuscular field is moving to screening programs and pre-symptomatic diagnosis with promising disease-modifying treatments. The aim of this paper is to discuss approach to NMD within the newborn period in line with clinical history, examination findings, and diagnostic tests.
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Asfixia Neonatal , Hipóxia-Isquemia Encefálica , Doenças Neuromusculares , Asfixia Neonatal/complicações , Humanos , Hipóxia-Isquemia Encefálica/complicações , Recém-Nascido , Neurônios Motores , Hipotonia Muscular , Doenças Neuromusculares/complicações , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/genéticaRESUMO
Neurologic complications have been associated with multisystem inflammatory syndrome in children, possibly involving autoimmune mechanisms. Here, we report a 6-year-old girl who developed myasthenia 11 weeks after severe acute respiratory syndrome coronavirus 2 infection and 8 weeks after the onset of severe multisystem inflammatory syndrome in children.
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COVID-19 , COVID-19/complicações , Criança , Feminino , Humanos , Síndrome de Resposta Inflamatória SistêmicaRESUMO
OBJECTIVES: Syncope is a common presenting symptom in the pediatric emergency department (PED). The etiology of pediatric syncope is generally benign. However, differentiating cardiac and other serious causes from benign causes of syncope are crucial. The aim of this study was to evaluate the change of physicians' behavior after introduction of an institutional protocol designed to act as a guide in the assessment and management of syncope patients in the PED. METHODS: This was a retrospective study, conducted at the PED of our University Children's Hospital. A "pediatric syncope approach protocol" was introduced on March 1, 2019 for quality improvement purposes. Documented information in the medical records, laboratory investigations and the patients' final diagnoses during the six-month periods before and after the protocol introduction were compared. RESULTS: 268 patients were included in the study (131 pre-protocol, 137 post-protocol patients). When compared with the pre-protocol group, there was a significant improvement in the documentation of syncope characteristics (prodromal findings, predisposing factors, association with exercise), cardiac, neurological and electrocardiographic (ECG) warning signs and ordering of cardiac markers in the post-protocol group. CONCLUSIONS: The introduction of the syncope approach protocol in PED has enabled an evidence-based and systematic evaluation and management of syncope patients, and reduced the rates of low-yield investigations. Sustained implementation of this protocol can have long-term benefits in the care of children with syncope at the emergency department.
Assuntos
Médicos , Síncope , Criança , Eletrocardiografia , Serviço Hospitalar de Emergência , Humanos , Estudos Retrospectivos , Síncope/diagnóstico , Síncope/etiologia , Síncope/terapiaRESUMO
PURPOSE: To obtain information on characteristics, management, current objective nutritional status and perception of nutritional status of children with cerebral palsy (CP) from healthcare professionals (HCPs) and caregivers. MATERIALS AND METHODS: A detailed survey of several items on eight main topics (general characteristics, motor function, comorbidities, therapies, anthropometry, feeding mode and problems and perceived nutritional status) was developed and tested for the study. Correlation between nutritional status and Gross Motor Function Classification System (GMFCS) levels was assessed using continuous variables (Z-scores for weight-for-age, height-for-age, weight-for-height, and body mass index-for-age), and categorical variables (being malnourished, stunted, or wasted). HCP and caregiver perceptions of the child's nutritional status as well as agreement between perceived and objective nutritional status and agreement between perceived nutritional status and concerns about the nutritional status were analyzed. RESULTS: Data were available for 497 participants from eight European countries. Poorer nutritional status was associated with higher (more severe) GMFCS levels. There was minimal agreement between perceived and objective nutritional status, both for HCPs and caregivers. Agreement between HCP and caregiver perceptions of the child's nutritional status was weak (weighted kappa 0.56). However, the concerns about the nutritional status of the child were in line with the perceived nutritional status. CONCLUSIONS: The risk of poor nutritional status is associated with more severe disability in children and adolescents with CP. There is a mismatch between HCP and caregiver perceptions of participants' nutritional status as well as between subjective and objective nutritional status. Our data warrant the use of a simple and objective screening tool in daily practice to determine nutritional status in children and adolescents with CP. Clinical trial registration: ClinicalTrials.gov Identifier: NCT03499288 (https://clinicaltrials.gov/ct2/show/NCT03499288). IMPLICATIONS FOR REHABILITATIONUse of the ESPGHAN recommendations and simple screening tools in daily practice is needed to improve nutritional care for individuals with CP.Attention should be paid to the differences in the perception of nutritional status of individuals with CP between professionals and caregivers to improve appropriate referral for nutritional support.Objective measures rather than the professional's perception need to be used to define the nutritional status of individuals with CP.