Острый рабдомиолиз

Rhabdomyolysis results from the rapid breakdown of skeletal muscle fibers, which leads to leakage of potentially toxic cellular contents into the systemic circulation. Acquired causes by direct injury to the sarcolemma are the most frequent. The inherited causes are: metabolic with failure of energy production, including mitochondrial fatty acid ß-oxidation defects, LPIN1 mutations, inborn errors of glycogenolysis and glycolysis, more rarely mitochondrial respiratory chain deficiency, purine defects and peroxysomalα-Methylacyl-CoA-racemase defect (AMACR); dystrophinopathies and myopathies; calcic causes with RYR1 mutations; inflammatory with myositis. Irrespective of the cause of rhabdomyolysis, the pathophysiologic events follow a common pathway, the ATP depletion leading to an increased intracellular calcium concentration and necrosis. Most episodes of rhabdomyolysis are triggered by an environmental stress, mostly fever. This condition is associated with two events, elevated temperature and high circulating levels of pro-inflammatory mediators such as cytokines and chemokines. We describe here an example of rhabdomyolysis related to high temperature, aldolase deficiency, in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. Thermolability was enhanced in patient myoblasts compared to control. The aldolase A deficiency was rescued by arginine supplementation in vitro. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines. Lipotoxicity may participate to myolysis. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a treatment for this severe disease. Some other diseases involved in rhabdomyolysis may implicate pro-inflammatory cytokines and may be proinflammatory diseases.Острый рабдомиолиз – драматичное внезапное разрушение мышечных волокон скелетных мышц. К генетическим этиологическим факторам относят: метаболические расстройства, сопровождаемые дефицитом окисления жирных кислот, дефицитом липина-1, аномалии гликогенолиза и гликолиза, реже – дефицит митохондриальной дыхательной цепи, дефицит пурина и пероксизмальный дефицит α-метил-ацил-КоА-рацемазы (α-methyl-acyl-CoA-acemase, AMACR); структурные патологии в рамках дистрофинопатий и миопатий; аномалии кальциевого обмена с мутациями в гене RYR1; воспалительные реакции, ассоциированные с миозитом. Независимо от причины, дефицит аденозинтрифосфата в миоците приводит к повышению содержания внутриклеточного кальция и некрозу мышечных волокон. Провоцирующим фактором рабдомиолиза могут быть экзогенные факторы, среди которых травматизация мышц является самой частой причиной рабдомиолиза метаболического генеза. В случае лихорадки следует учитывать 2 фактора: повышение температуры тела и существование провоспалительных цитокинов. В статье описан случай рабдомиолиза у 3 детей от близкородственного брака, спровоцированный гипертермией и вызванный дефицитом альдолазы А, не сопровождаемой гемолитической анемией. В рассматриваемом случае миоглобинурия была всегда вызвана фебрильной температурой. В свою очередь, фермент альдолаза-А обладает тканеспецифичной термолабильностью: при тестируемых температурах он обнаружен в миобластах, но не в эритроцитах, что объясняет специфическую симптоматику у описываемых пациентов. Существуют предположения, что в клеточной липотоксичности участвуют так называемые жировые капли. В ходе исследований in vitro дефицит альдолазы А был возмещен добавлением аргинина. Другие типы рабдомиолиза метаболического генеза, вероятно, являются провоспалительными заболеваниями.перевод: Мария Олеговна Ковальчу

The phenotypic spectrum of WWOX -related disorders: 20 additional cases of WOREE syndrome and review of the literature

Purpose: Germline WWOX pathogenic variants have been associated with disorder of sex differentiation (DSD), spinocerebellar ataxia (SCA), and WWOX-related epileptic encephalopathy (WOREE syndrome). We review clinical and molecular data on WWOX-related disorders, further describing WOREE syndrome and phenotype/genotype correlations. Methods: We report clinical and molecular findings in 20 additional patients from 18 unrelated families with WOREE syndrome and biallelic pathogenic variants in the WWOX gene. Different molecular screening approaches were used (quantitative polymerase chain reaction/multiplex ligation-dependent probe amplification [qPCR/MLPA], array comparative genomic hybridization [array-CGH], Sanger sequencing, epilepsy gene panel, exome sequencing). Results: Two copy-number variations (CNVs) or two single-nucleotide variations (SNVs) were found respectively in four and nine families, with compound heterozygosity for one SNV and one CNV in five families. Eight novel missense pathogenic variants have been described. By aggregating our patients with all cases reported in the literature, 37 patients from 27 families with WOREE syndrome are known. This review suggests WOREE syndrome is a very severe epileptic encephalopathy characterized by absence of language development and acquisition of walking, early-onset drug-resistant seizures, ophthalmological involvement, and a high likelihood of premature death. The most severe clinical presentation seems to be associated with null genotypes. Conclusion: Germline pathogenic variants in WWOX are clearly associated with a severe early-onset epileptic encephalopathy. We report here the largest cohort of individuals with WOREE syndrome

Remediation of Allophonic Perception and Visual Attention Span in Developmental Dyslexia: A Joint Assay

International audienc

Relationships between Categorical Perception of Phonemes, Phoneme Awareness, and Visual Attention Span in Developmental Dyslexia

International audienceWe tested the hypothesis that the categorical perception deficit of speech sounds in developmental dyslexia is related to phoneme awareness skills, whereas a visual attention (VA) span deficit constitutes an independent deficit. Phoneme awareness tasks, VA span tasks and categorical perception tasks of phoneme identification and discrimination using a d/t voicing continuum were administered to 63 dyslexic children and 63 control children matched on chronological age. Results showed significant differences in categorical perception between the dyslexic and control children. Significant correlations were found between categorical perception skills, phoneme awareness and reading. Although VA span correlated with reading, no significant correlations were found between either categorical perception or phoneme awareness and VA span. Mediation analyses performed on the whole dyslexic sample suggested that the effect of categorical perception on reading might be mediated by phoneme awareness. This relationship was independent of the participants' VA span abilities. Two groups of dyslexic children with a single phoneme awareness or a single VA span deficit were then identified. The phonologically impaired group showed lower categorical perception skills than the control group but categorical perception was similar in the VA span impaired dyslexic and control children. The overall findings suggest that the link between categorical perception, phoneme awareness and reading is independent from VA span skills. These findings provide new insights on the heterogeneity of developmental dyslexia. They suggest that phonological processes and VA span independently affect reading acquisition

Evaluations et implications des Troubles Auditifs Centraux (TAC) dans la dysphasie : Etude de cas

International audienc

Clustering syncope in a young male with temporal lobe seizures.

International audienceWe report the case of a male aged 2 years 6 months with left temporal lobe epilepsy who presented with ictal bradycardia syndrome leading to asystole. The clinical presentation was remarkable for the occurrence of clustering syncope. A seizure was recorded on a video electroencephalogram- electrocardiogram and analyzed. A cardiac pacemaker was implanted and antiepileptic drug treatment was initiated. We suggest that clustering of syncope is an important feature in the presentation of epilepsy in a young child

The Dynamics of Handwriting Improves the Automated Diagnosis of Dysgraphia

Cet article est en open-access archive, avant publicationHandwriting disorder (termed dysgraphia) is a far from a singular problem as nearly 8.6% of the population in France is considered dysgraphic. Moreover, research highlights the fundamental importance to detect and remediate these handwriting difficulties as soon as possible as they may affect a child's entire life, undermining performance and self-confidence in a wide variety of school activities. At the moment, the detection of handwriting difficulties is performed through a standard test called BHK. This detection, performed by therapists, is laborious because of its high cost and subjectivity. We present a digital approach to identify and characterize handwriting difficulties via a Recurrent Neural Network model (RNN). The child under investigation is asked to write on a graphics tablet all the letters of the alphabet as well as the ten digits. Once complete, the RNN delivers a diagnosis in a few milliseconds and demonstrates remarkable efficiency as it correctly identifies more than 90% of children diagnosed as dysgraphic using the BHK test. The main advantage of our tablet-based system is that it captures the dynamic features of writingsomething a human expert, such as a teacher, is unable to do. We show that incorporating the dynami

The Dynamics of Handwriting Improves the Automated Diagnosis of Dysgraphia

Cet article est en open-access archive, avant publicationHandwriting disorder (termed dysgraphia) is a far from a singular problem as nearly 8.6% of the population in France is considered dysgraphic. Moreover, research highlights the fundamental importance to detect and remediate these handwriting difficulties as soon as possible as they may affect a child's entire life, undermining performance and self-confidence in a wide variety of school activities. At the moment, the detection of handwriting difficulties is performed through a standard test called BHK. This detection, performed by therapists, is laborious because of its high cost and subjectivity. We present a digital approach to identify and characterize handwriting difficulties via a Recurrent Neural Network model (RNN). The child under investigation is asked to write on a graphics tablet all the letters of the alphabet as well as the ten digits. Once complete, the RNN delivers a diagnosis in a few milliseconds and demonstrates remarkable efficiency as it correctly identifies more than 90% of children diagnosed as dysgraphic using the BHK test. The main advantage of our tablet-based system is that it captures the dynamic features of writingsomething a human expert, such as a teacher, is unable to do. We show that incorporating the dynami

Predicted and observed discrimination curves for the Dyslexic subgroup with a single phoneme awareness deficit (PA DYS) and the Control Group (CTL).

<p>Predicted and observed discrimination curves for the Dyslexic subgroup with a single phoneme awareness deficit (PA DYS) and the Control Group (CTL).</p

Phonemic boundary: location along the VOT continuum and correlations with locations of the predicted and expected discrimination peaks.

<p>Phonemic boundary: location along the VOT continuum and correlations with locations of the predicted and expected discrimination peaks.</p