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OBJECTIVES: Intrathecal baclofen pump associated central nervous system (CNS) infection and meningitis is a rare but serious complication and may have dire consequences. Due to bacterial biofilm formation, the optimal treatment strategy is usually for removal of the pump, followed by systemic antibiotics for treatment of local and CNS infection. We describe this case of a patient with recurrent Staphylococcus aureus pump site empyema and meningitis leading to status dystonicus, who was successfully managed with radical debridement and intrareservoir baclofen-vancomycin co-infusion. MATERIALS AND METHODS: We retrospectively report a case of infected intrathecal baclofen pump with meningitis and provide a full review of literature. CONCLUSIONS: To the best of our knowledge, this is the first reported case of intrathecal baclofen (ITB)-associated pump site empyema and meningitis successfully treated with this technique. In selected cases where surgical explantation is deemed not feasible, this method can provide clinicians with an additional option for pump salvage and retention, while eradicating CNS infection and maintaining optimal control of spasticity and dystonia.
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Meningite , Relaxantes Musculares Centrais , Baclofeno/uso terapêutico , Desbridamento , Humanos , Bombas de Infusão Implantáveis , Injeções Espinhais , Meningite/tratamento farmacológico , Relaxantes Musculares Centrais/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Estudos Retrospectivos , Vancomicina/uso terapêuticoRESUMO
Congenital muscular dystrophies (CMDs) are clinically and genetically heterogeneous conditions. We launched a nationwide study to determine the frequency of CMD in the Chinese population and assess the status of diagnosis and disease management for CMD in China. Cases were chosen from databases in 34 tertiary academic hospitals from 29 first-level administrative divisions (provinces, municipalities, autonomous regions, and special administrative regions), and medical records were reviewed to confirm the diagnoses. The study included 409 patients, of those patients who consented to genetic testing (n = 340), mutations were identified in 286 of them. The most common forms identified were LAMA2-related CMD (36.4%), followed by COL6-related CMD (23.2%) and α-dystroglycanopathy (21.0%). The forms of CMD related to mutations in LMNA and SEPN1 were less frequent (12.5% and 2.4%, respectively). We also recorded a significant difference in the diagnostic capabilities and disease management of CMD, with this being relatively backward in research centers from less developed regions. We provide, for the first time, comprehensive epidemiologic information of CMD in a large cohort of Chinese people. To our knowledge, this is the largest sample size of its kind so far highlighting the prevalence of CMD in China.
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Distrofias Musculares/epidemiologia , Distrofias Musculares/genética , Alelos , China/epidemiologia , Diagnóstico Diferencial , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos , Humanos , Masculino , Distrofias Musculares/diagnóstico , Mutação , Fenótipo , Vigilância da População , PrevalênciaRESUMO
AIM: Increasing preimplantation genetic testing (PGT) cycles are being performed in Hong Kong. This study aims to evaluate the knowledge, attitude and ethical consideration of Chinese couples toward PGT. METHODS: Couples requesting PGT between June 2013 and March 2014 were invited to complete a questionnaire. RESULTS: Total 49 couples (49 women, 47 men) completed the questionnaires. Eighteen couples (37%) were waiting for PGT (pre-PGT group), 15 couples (31%) were undergoing PGT (PGT group) and 16 couples (32%) had completed at least one PGT cycle (post-PGT group). Only 53% of the couples could tell the recurrent risk, and 31% (with monogenic disorders) could tell the mode of inheritance of their condition. The acceptability of PGT (>80%) and attitude toward the embryo fate (58-78%) were good. The post-PGT group had more concern than the PGT and pre-PGT groups on the prenatal diagnostic testing (**P = 0.007). 12.5% of the couples worried about the transfer of healthy embryos with carrier state and they all had monogenic disorders. If the prenatal testing confirmed an affected fetus, a higher percentage (32%) in the Post-PGT group disagreed to terminate the pregnancy in contrast to a much lower 6% in the pre-PGT group (**P = 0.02). Three-quarter of the couples opted to tell their child about their conception through PGT. CONCLUSION: Chinese couples in Hong Kong had an overall good acceptability and positive attitude toward PGT. We appreciate the difficulties the couples have gone through PGT. A checklist on what to cover pre-during-post-PGT in the counseling process is needed.
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Doenças Genéticas Inatas/diagnóstico , Testes Genéticos , Conhecimentos, Atitudes e Prática em Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Diagnóstico Pré-Implantação , Técnicas de Reprodução Assistida , Adulto , Estudos Transversais , Feminino , Hong Kong , Humanos , MasculinoRESUMO
Currently there is a lack of randomized trial data examining the use of the antiviral nirmatrelvir/ritonavir in paediatric patients with SARS-CoV-2 infection. This target trial emulation study aims to address this gap by evaluating the use of nirmatrelvir/ritonavir in non-hospitalized paediatric patients aged 12-17 years with SARS-CoV-2 Omicron variant infection. Among paediatric patients diagnosed between 16th March 2022 and 5th February 2023, exposure was defined as outpatient nirmatrelvir/ritonavir treatment within 5 days of symptom onset or COVID-19 diagnosis. Primary outcome was 28 day all-cause mortality or all-cause hospitalization, while secondary outcomes were 28 day in-hospital disease progression, 28 day COVID-19-specific hospitalization, multisystem inflammatory syndrome in children (MIS-C), acute liver injury, acute renal failure, and acute respiratory distress syndrome. Overall, 49,378 eligible paediatric patients were included. Nirmatrelvir/ritonavir treatment was associated with reduced 28 day all-cause hospitalization (absolute risk reduction = 0.23%, 95%CI = 0.19%-0.31%; relative risk = 0.66, 95%CI = 0.56-0.71). No events of mortality, in-hospital disease progression, or adverse clinical outcomes were observed among nirmatrelvir/ritonavir users. The findings confirmed the effectiveness of nirmatrelvir/ritonavir in reducing all-cause hospitalization risk among non-hospitalized pediatric patients with SARS-CoV-2 Omicron variant infection.
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Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Hospitalização , Ritonavir , SARS-CoV-2 , Humanos , Ritonavir/uso terapêutico , Criança , Adolescente , Feminino , Masculino , Antivirais/uso terapêutico , COVID-19/mortalidade , COVID-19/virologia , COVID-19/complicações , Resultado do Tratamento , Síndrome de Resposta Inflamatória SistêmicaRESUMO
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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Background: Epilepsy-associated dysbiosis in gut microbiota has been previously described, but the mechanistic roles of the gut microbiome in epileptogenesis among children with cerebral palsy (CP) have yet to be illustrated. Methods: Using shotgun metagenomic sequencing coupled with untargeted metabolomics analysis, this observational study compared the gut microbiome and metabolome of eight children with non-epileptic cerebral palsy (NECP) to those of 13 children with cerebral palsy with epilepsy (CPE). Among children with CPE, 8 had drug-sensitive epilepsy (DSE) and five had drug-resistant epilepsy (DRE). Characteristics at enrollment, medication history, and 7-day dietary intake were compared between groups. Results: At the species level, CPE subjects had significantly lower abundances of Bacteroides fragilis and Dialister invisus but higher abundances of Phascolarctobacterium faecium and Eubacterium limosum. By contrast, DRE subjects had a significantly higher colonization of Veillonella parvula. Regarding microbial functional pathways, CPE subjects had decreased abundances of pathways for serine degradation, quinolinic acid degradation, glutamate degradation I, glycerol degradation, sulfate reduction, and nitrate reduction but increased abundances of pathways related to ethanol production. As for metabolites, CPE subjects had higher concentrations of kynurenic acid, 2-oxindole, dopamine, 2-hydroxyphenyalanine, 3,4-dihydroxyphenylglycol, L-tartaric acid, and D-saccharic acid; DRE subjects had increased concentrations of indole and homovanilic acid. Conclusions: In this study, we found evidence of gut dysbiosis amongst children with cerebral palsy and epilepsy in terms of gut microbiota species, functional pathways, and metabolites. The combined metagenomic and metabolomic analyses have shed insights on the potential roles of B. fragilis and D. invisus in neuroprotection. The combined analyses have also provided evidence for the involvement of GMBA in the epilepsy-related dysbiosis of kynurenine, serotonin, and dopamine pathways and their complex interplay with neuroimmune and neuroendocrinological pathways.
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OBJECTIVES: The aim of this study is to quantify the mortality rate, direct healthcare costs, and cumulative life costs of pediatric patients with spinal muscular atrophy (SMA) type 1, type 2, and type 3 born in Hong Kong. METHODS: Data were collected from genetically confirmed SMA patients born in or after 2000 from the Hospital Authority medical database. Patients were followed up from birth until they died, left Hong Kong, reached 18 years, or initiated disease-modifying treatment. Study outcomes included incidence risks of mortality, cumulative direct medical costs-attendances of special outpatient clinics, emergency department, allied health services, and mean length of stay in hospitals over time. Total direct medical costs were calculated as unit costs multiplied by utilization frequencies of corresponding healthcare services at each age. RESULTS: Seventy-one patients with SMA were included. Over a median follow-up period of 6 years, the overall incidence rate of death was 5.422/100 person-years (95%CI 3.542-7.945/100 person-years). 67.7% and 11% of deaths occurred in SMA1 and SMA2 groups, respectively. The median age of death was 0.8 years in SMA1 and 10.9 years in SMA2. The mean cumulative direct medical costs in overall SMA, SMA1, SMA2 and SMA3 groups per patient were US$935,570, US$2,393,250, US$413,165, and US$40,735, respectively. INTERPRETATION: Our results confirmed a significantly raised mortality and extremely high healthcare burden for patients with SMA especially SMA type 1 and 2 without disease-modifying treatment. Study evaluating health and economic impact of newborn screening and early treatment is needed.
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Atrofia Muscular Espinal , Atrofias Musculares Espinais da Infância , Recém-Nascido , Criança , Humanos , Lactente , Atenção à Saúde , Custos de Cuidados de Saúde , Serviços de SaúdeRESUMO
There has been a rapid surge of hospitalization due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants globally. The severity of Omicron BA.2 in unexposed, unvaccinated, hospitalized children is unknown. We investigated the severity and clinical outcomes of COVID-19 infection during the Omicron wave in uninfected, unvaccinated hospitalized children and in comparison with influenza and parainfluenza viral infections. This population-based study retrieved data from the HK territory-wide CDARS database of hospitalisations in all public hospitals and compared severe outcomes for the Omicron BA.2-dominant fifth wave (5-28 February 2022, n = 1144), and influenza and parainfluenza viruses (1 January 2015-31 December 2019, n = 32212 and n = 16423, respectively) in children 0-11 years old. Two deaths (0.2%) out of 1144 cases during the initial Omicron wave were recorded. Twenty-one (1.8%) required PICU admission, and the relative risk was higher for Omicron than influenza virus (n = 254, 0.8%, adjusted RR = 2.1, 95%CI 1.3-3.3, p = 0.001). The proportion with neurological complications was 15.0% (n = 171) for Omicron, which was higher than influenza and parainfluenza viruses (n = 2707, 8.4%, adjusted RR = 1.6, 95%CI 1.4-1.9 and n = 1258, 7.7%, adjusted RR = 1.9, 95%CI 1.6-2.2, p < 0.001 for both, respectively). Croup occurred for Omicron (n = 61, 5.3%) more than influenza virus (n = 601, 1.9%, adjusted RR = 2.0, 95%CI 1.5-2.6, p < 0.001) but not parainfluenza virus (n = 889, 5.4%). Our findings showed that for hospitalized children who had no past COVID-19 or vaccination, Omicron BA.2 was not mild. Omicron BA.2 appeared to be more neuropathogenic than influenza and parainfluenza viruses. It targeted the upper airways more than influenza virus.
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COVID-19 , Influenza Humana , Orthomyxoviridae , Infecções por Paramyxoviridae , Criança , Criança Hospitalizada , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Infecções por Paramyxoviridae/epidemiologia , SARS-CoV-2RESUMO
BACKGROUND: Children with special educational needs (SEN) are more vulnerable during the COVID-19 pandemic with risk of poor mental wellbeing and child maltreatment. OBJECTIVE: To examine the impact of COVID-19 on the mental health of children with SEN and their maltreatment risk. PARTICIPANTS AND SETTING: 417 children with SEN studying at special schools and 25,427 children with typical development (TD) studying at mainstream schools completed an online survey in April 2020 in Hong Kong during school closures due to COVID-19. METHOD: Emotional/behavioural difficulties, quality of life and parental stress of children with SEN were compared with typically developed children using mixed effect model. Linear regression analyses were performed to explore factors associated with child emotional/behavioural difficulties and parental stress during the pandemic. Chi-square test was performed to detect the differences in maltreatment risk before and during COVID-19. RESULTS: Children with SEN had significantly poorer overall quality of life (68.05 vs 80.65, p < 0.01). 23.5% of children had at least one episode of severe physical assault and 1.9% experienced very severe physical assault during COVID-19. Rates of physical assault increased significantly (59.8% vs. 71.2% p < 0.001) while children with mental disorders had increased risk of severe physical assault comparing to those without mental disorders (RR = 1.58, ê2 = 5.19 p = 0.023). CONCLUSION: Children with SEN had poorer mental health than typically developed children during the COVID-19 pandemic. Maltreatment risk for children with SEN is higher in comparison to pre-COVID-19 era. Surveillance of child maltreatment, continuity of medical and rehabilitation care to support children with SEN are essential during a disease pandemic.
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COVID-19 , Saúde Mental , COVID-19/epidemiologia , Criança , Humanos , Pandemias , Qualidade de Vida , Instituições AcadêmicasRESUMO
BACKGROUND: Neuromuscular disorders (NMDs) comprise a group of heterogeneous genetic diseases with a broad spectrum of overlapping the clinical presentations that makes diagnosis challenging. Notably, the recent introduction of whole-exome sequencing (WES) is introducing rapid changes on the genetic diagnosis of NMDs. We aimed to investigate the diagnostic value of WES for pediatric-onset NMDs. METHODS: We applied integrated diagnostic approach and performed WES in 50 Chinese subjects (30 males, 20 females) with undiagnosed pediatric-onset NMDs despite previous specific tests. The patients were categorized in four subgroups according to phenotyping and investigation findings. Variants on NMDs gene list and open exome analysis for those with initial negative findings were identified. RESULTS: WES identified causative variants in ACTA1 (n = 2), POMT1, COL6A1 (n = 2), MTMR2, LMNA, SELENON, DNM2, TGFB1, MPZ, IGHMBP2, and LAMA2 in 13 patients. Two subjects have variants of uncertain significance (VUSs) in TTN and SCN11A, unlikely to be pathogenic due to incompatible phenotypes. The mean interval time from symptom onset to genetic diagnosis was 10.4 years (range from 1 month to 33 years). The overall diagnostic yield of WES in our cohort was 26%. Open exome analysis was necessary to identify the pathogenic variant in TGFB1 that caused skeletal dysplasia with neuromuscular presentation. CONCLUSION: Our study shows a clear role of WES in the pathway of integrated diagnostic approach to shorten the diagnostic odyssey in patients with rare NMDs.
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Sequenciamento do Exoma/métodos , Testes Genéticos/métodos , Doenças Neuromusculares/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Loci Gênicos , Testes Genéticos/normas , Humanos , Lactente , Masculino , Mutação , Doenças Neuromusculares/diagnóstico , Valor Preditivo dos Testes , Sequenciamento do Exoma/normasRESUMO
BACKGROUND: Autosomal recessive or compound heterozygous mutations in KLHL40 cause nemaline myopathy 8, which is one of the most severe forms of nemaline myopathy. The KLHL40 c.1516A>C variant has recently been reported as a founder mutation in southern Chinese. METHODS: We report six cases of nemaline myopathy 8 which involves the c.1516A>C variant, from five unrelated families of non-consanguineous southern Chinese. The pre- and postnatal phenotypes of these cases were reviewed with emphasis on prenatal clinical features. Genetic testing for the founder mutation was performed on three patients with homozygous mutations. RESULTS: Common prenatal features included reduced fetal movement, polyhydramnios, breech presentation, and clubfeet. Two pregnancies were terminated. Four live-born patients had postnatal features typical of nemaline myopathy 8. The length of survival ranged from 49 days to 17 months, with respiratory failure and infections being the principal causes of death. Haplotype analysis in three patients with homozygous mutation showed a shared haplotype block of 1.1727 cM spanning over the c.1516A>C variant, suggesting it is a southern Chinese-specific founder mutation. CONCLUSION: Analysis of the KLHL40 c.1516A>C variant should be considered in prenatal diagnosis of Chinese pregnant patients with suspected congenital neuromuscular disorders or with significant family history of congenital myopathies.
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Efeito Fundador , Proteínas Musculares/genética , Miopatias da Nemalina/genética , Feto Abortado/patologia , Adulto , China , Feminino , Haplótipos , Homozigoto , Humanos , Recém-Nascido , Miopatias da Nemalina/patologia , Fenótipo , Mutação PuntualRESUMO
Spinocerebellar ataxia 35 (SCA35) has been associated with pathogenic mutations in the gene TGM6. In a Chinese exome sequencing cohort, we identified 8 families with reported TGM6 variants sharing no features of SCA35. Considering this finding, we reviewed the public database gnomAD and found these variants to be significantly more common in the East Asians than in other ethnic groups (Pâ¯<â¯0.0001). Gene constraint metrics showed that both missense and loss-of-function variants in TGM6 are likely to be tolerated and there is no regional constraint. By performing inflation analysis, it demonstrated that the cumulative frequency of TGM6 reported pathogenic variants is at least 111-fold inflated over disease prevalence of all autosomal dominant SCAs, indicating a high chance of misdiagnosis or low penetrance. Misclassification of benign or low penetrant variants as pathogenic is a significant problem that often results in genetic misdiagnosis. This highlights the necessity of evaluating variant pathogenicity with sequencing of genomes from diverse populations, both from asymptomatic controls and phenotypically different patients, in order to ensure accurate classification of variants.
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Predisposição Genética para Doença/genética , Ataxias Espinocerebelares/genética , Transglutaminases/genética , Adolescente , Adulto , Povo Asiático/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Linhagem , Adulto JovemRESUMO
Mutations in ACTA1 cause a group of myopathies with expanding clinical and histopathological heterogeneity. We describe three patients with severe ACTA1-related myopathy who have muscle fiber cytoplasmic bodies but no classic nemaline rods. Patient 1 is a five-year-old boy who presented at birth with severe weakness and respiratory failure, requiring mechanical ventilation. Whole exome sequencing identified a heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation. Patients 2 and 3 were twin boys with hypotonia, severe weakness, and respiratory insufficiency at birth requiring mechanical ventilation. Both died at 6 months of age. The same heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation was identified by whole exome sequencing. We conclude that clinically severe ACTA1-related myopathy can present with muscle morphological findings suggestive of cytoplasmic body myopathy in the absence of definite nemaline rods. The Asn94Lys mutation in skeletal muscle sarcomeric α-actin may be linked to this histological appearance. These novel ACTA1 cases also illustrate the successful application of whole exome sequencing in directly arriving at a candidate genetic diagnosis in patients with unexpected phenotypic and histologic features for a known neuromuscular gene.
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Actinas/genética , Corpos de Inclusão/patologia , Doenças Musculares/genética , Doenças Musculares/patologia , Miopatias da Nemalina/genética , Miopatias da Nemalina/patologia , Pré-Escolar , Humanos , Masculino , Músculo Esquelético/patologia , Doenças Musculares/complicações , Mutação , Miopatias da Nemalina/complicações , Linhagem , Gêmeos , Sequenciamento do ExomaRESUMO
We report a young boy who presented with progressive weakness of lower extremities associated with areflexia and abnormal electrophysiological findings initially suggestive of chronic inflammatory demyelinating polyneuropathy. Initial lumbosacral spinal magnetic resonance imaging (MRI) showed thickened descending spinal nerve roots only. Immunomodulating therapy was given but with limited clinical response. Repeated spine magnetic resonance imaging showed cauda equina and also new spinal cord extramedullary contrast enhancement. The initial extensive investigations including open biopsy did not point to any specific diagnosis. Only through pursuing a repeated biopsy, the diagnosis of the spinal peripheral primitive neuroectodermal tumor was confirmed. This case highlights the diagnostic challenges of the spinal peripheral primitive neuroectodermal tumor that could have an initial chronic inflammatory demyelinating polyneuropathy-like presentation. The literature review confirms that this is a rare condition and cauda equina origin has only been reported in adults and teenagers, and this is the first reported case in a young child.
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Tumores Neuroectodérmicos Primitivos/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Criança , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética , Masculino , Medula Espinal/patologia , Nervos Espinhais/patologiaRESUMO
The aim of this collaborative study on Duchenne muscular dystrophy and Becker muscular dystrophy is to determine the prevalence and to develop data on such patients as a prelude to the development of registry in Hong Kong. Information on clinical and molecular findings, and patient care, was systematically collected in 2011 and 2012 from all Pediatric Neurology Units in Hong Kong. Ninety patients with dystrophinopathy were identified, and 83% has Duchenne muscular dystrophy. The overall prevalence of dystrophinopathy in Hong Kong in 2010 is 1.03 per 10 000 males aged 0 to 24 years. Among the Duchenne group, we observed a higher percentage (40.6%) of point mutations with a lower percentage (45.3%) of exon deletions in our patients when compared with overseas studies. Although we observed similar percentage of Duchenne group received scoliosis surgery, ventilation support, and cardiac treatment when compared with other countries, the percentage (25%) of steroid use is lower.
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We report an eleven year old girl with early motor difficulties initially diagnosed with a peripheral neuropathy in another hospital based on abnormal electrophysiological findings. Our clinical assessment did not highlight obvious clinical features supporting a peripheral neuropathy but evidence of mild proximal weakness. Electrophysiological studies performed at our hospital revealed evidence of a sensorimotor demyelinating polyneuropathy with possible axonal involvement. Brain magnetic resonance imaging (MRI) revealed subtle white matter signal abnormalities, interpreted as nonspecific. Given the patient's proximal weakness and a mildly elevated serum creatine kinase, we performed a muscle biopsy. The muscle had mildly dystrophic features and subtly depleted laminin α2 expression. There was diffusely upregulated laminin α5 expression, and depletion of laminin α2 in intramuscular motor nerves, which made us suspect a partial laminin α2 (merosin) deficiency. Muscle MRI showed predominant posterior and medial compartments involvement. The patient was found to have autosomal recessively inherited double heterozygous LAMA2 mutations. This case illustrates the mild end of the partial merosin deficiency phenotypic spectrum, and highlights how careful assessment of laminin α2 expression in intramuscular motor nerves can be a helpful diagnostic clue in partial merosin deficiency.
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Laminina/genética , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/genética , Biópsia , Encéfalo/patologia , Códon sem Sentido , Diagnóstico Diferencial , Feminino , Heterozigoto , Humanos , Imageamento por Ressonância Magnética , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular do Cíngulo dos Membros/patologia , Distrofia Muscular do Cíngulo dos Membros/fisiopatologia , Condução Nervosa , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/fisiopatologiaRESUMO
Congenital myasthenic syndrome caused by endplate acetylcholinesterase deficiency constitutes a rare autosomal recessive disease. We describe a child with early-onset ptosis, complete ophthalmoplegia, facial and proximal muscle weakness, easy fatigability, a decremental electromyographic response, and a repetitive compound muscle action potential not improved by anti-acetylcholinesterase medication. Mutation analysis of the collagenic tail of endplate acetylcholinesterase (COLQ) that encodes the collagenic structural subunit of acetylcholinesterase revealed two canonic splice-site mutations: a previously identified IVS15 + 1G>A mutation and a novel IVS2 - 1G>A mutation. Treatment with albuterol resulted in progressive improvement of muscle strength, exercise tolerance, and ophthalmoplegia. Further studies are needed of the efficacy of albuterol in different types of congenital myasthenic syndrome and the physiologic basis of its beneficial effects.
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Acetilcolinesterase/deficiência , Albuterol/uso terapêutico , Síndromes Miastênicas Congênitas/tratamento farmacológico , Síndromes Miastênicas Congênitas/enzimologia , Junção Neuromuscular/enzimologia , Acetilcolinesterase/biossíntese , Acetilcolinesterase/genética , Albuterol/farmacologia , Criança , Humanos , Masculino , Síndromes Miastênicas Congênitas/diagnóstico , Junção Neuromuscular/efeitos dos fármacos , Resultado do TratamentoRESUMO
A young girl with antibodies to the N-methyl-D-aspartate receptor presented with a clinical syndrome suggestive of dyskinetic encephalitis lethargica with neuropsychiatric features at presentation, movement disorder, mutism, sleep disorder, and seizures. Persistent lesions in the white matter and pons were observed in magnetic resonance imaging of the brain, findings that have not been described previously in N-methyl-D-aspartate receptor antibody encephalitis.