Our knowledge of the genetic diversity and host ranges of viruses is fragmentary. This is particularly true for the Parvoviridae family. Genetic diversity studies of single stranded DNA viruses ...within this family have been largely focused on arthropod- and vertebrate-infecting species that cause diseases of humans and our domesticated animals: a focus that has biased our perception of parvovirus diversity. While metagenomics approaches could help rectify this bias, so too could transcriptomics studies. Large amounts of transcriptomic data are available for a diverse array of animal species and whenever this data has inadvertently been gathered from virus-infected individuals, it could contain detectable viral transcripts. We therefore performed a systematic search for parvovirus-related sequences (PRSs) within publicly available transcript, genome and protein databases and eleven new transcriptome datasets. This revealed 463 PRSs in the transcript databases of 118 animals. At least 41 of these PRSs are likely integrated within animal genomes in that they were also found within genomic sequence databases. Besides illuminating the ubiquity of parvoviruses, the number of parvoviral sequences discovered within public databases revealed numerous previously unknown parvovirus-host combinations; particularly in invertebrates. Our findings suggest that the host-ranges of extant parvoviruses might span the entire animal kingdom.
Mucopolysaccharidosis type I-Hurler syndrome (MPSI-H) is a lysosomal storage disease characterized by severe physical symptoms and cognitive decline. Early treatment with hematopoietic cell ...transplant (HSCT) is critical to the survival of these patients. While survival rates and short-term outcomes are known to be improved by HSCT, the long-term cognitive, adaptive and psychosocial functional outcomes of children with (MPSI-H) post-HSCT are not well documented. This manuscript focuses on retrospective long-term follow-up (7-33 years) of 25 MPSI-H patients, transplanted between 1986 and 2011.
The median age at transplantation was 21 months (range 12-57 months). Except for one death, all successfully transplanted MPSI-H patients surviving at least 1 year after HSCT are alive to-date, with a median age of 21 years (range 8-36 years) at the last follow-up evaluation. A majority of HSCT grafts were bone marrow transplants (BMT), resulting in durable full chimerism in 18 (72%). Pre-HSCT, the onset of first symptoms occurred very early, at a median age of 3 months (range birth-16 months). The most prevalent symptoms before MPSI-H diagnosis involved progressive dysostosis multiplex; almost all patients suffered from hip dysplasia and thoracolumbar spine Kyphosis. Despite HSCT, considerable residual disease burden and ensuing corrective surgical interventions were observed in all, and at every decade of follow-up post HSCT. Late-onset psychiatric manifestations were significant (n = 17 patients; 68%), including depression in 13 patients at a median onset age of 18 years (range 13-31 years), hyperactivity and attention deficit disorder (n = 4), and multiple acute psychotic episodes (APE), independent of depression observed (n = 3) at a median onset age of 18 years (range 17-31 years). The adult Welscher Intelligence Scale results (n = 16) were heterogenous across the four scale dimensions; overall lower scores were observed on both working memory index (median WMI = 69.5) and processing speed index (median PSI = 65), whereas verbal comprehension index (median VCI = 79) and perceptual reasoning index (median PRI = 74) were higher.
With advanced treatment options, MPSI-H are living into 3rd and 4th decades of life, however not disease free and with poor adaptation. Residual disease (loss of mobility, limited gross and fine motor skills; low cognitive ability; suboptimal cardiopulmonary function, vision and hearing) negatively impacts the quality of life and psychosocial functioning of affected individuals.
The adaptive hypothesis invoked to explain why parasites harm their hosts is known as the trade-off hypothesis, which states that increased parasite transmission comes at the cost of shorter ...infection duration. This correlation arises because both transmission and disease-induced mortality (i.e. virulence) are increasing functions of parasite within-host density. There is, however, a glaring lack of empirical data to support this hypothesis. Here, we review empirical investigations reporting to what extent within-host viral accumulation determines the transmission rate and the virulence of vector-borne plant viruses. Studies suggest that the correlation between within-plant viral accumulation and transmission rate of natural isolates is positive. Unfortunately, results on the correlation between viral accumulation and virulence are very scarce. We found only very few appropriate studies testing such a correlation, themselves limited by the fact that they use symptoms as a proxy for virulence and are based on very few viral genotypes. Overall, the available evidence does not allow us to confirm or refute the existence of a transmission–virulence trade-off for vector-borne plant viruses. We discuss the type of data that should be collected and how theoretical models can help us refine testable predictions of virulence evolution.
McArdle disease, or glycogen storage disease type V (GSD 5), is a rare metabolic myopathy linked to an autosomal recessive myophosphorylase deficiency.
We report the case of a 17-year-old male ...patient who was referred to the emergency department for the management of acute inflammatory low back pain, without traumatic context, associated with an increase of CK at 66,336 UI/L (N<192UI/L) and a CRP at 202mg/L. The immunological assessment was negative and the spinal MRI showed images in favor of necrotizing fasciitis affecting the erector spinae muscles, among others. Faced with the description of difficulties in practicing physical activities since childhood and a non-ischaemic forearm exercise test showing no elevation in lactacidemia, genetic tests were carried out, finding two heterozygous variants in the PYGM gene: c.1963G>A (p.Glu655Lys) class 5 and c.2178-1G>A class 4, confirming the diagnosis of McArdle disease.
GSD 5 is a disease characterized essentially by muscular fatigability during exercise. The case reported here is original in the clinical circumstances leading to the diagnosis, i.e., inaugural acute low back pain with rhabdomyolysis. This symptomatology had already been described before, but in a patient whose diagnosis was already known. Spinal MRI showed non-specific muscle inflammation and necrosis. Muscle biopsy only found necrosis but no pathological elements typical of the diagnosis. If the symptoms are suggestive, it may be preferable to directly perform a non-ischaemic forearm exercise test, in order to go directly to molecular genetic analysis. There is no specific curative treatment of GSD 5. However, some measures can be implemented to limit the symptoms, such as learning physical exercises, limiting intense efforts and adopting dietary recommendations.
Metagenomics studies have revolutionized the field of biology by revealing the presence of many previously unisolated and uncultured micro-organisms. However, one of the main problems encountered in ...metagenomic studies is the high percentage of sequences that cannot be assigned taxonomically using commonly used similarity-based approaches (e.g. BLAST or HMM). These unassigned sequences are allegorically called « dark matter » in the metagenomic literature and are often referred to as being derived from new or unknown organisms. Here, based on published and original metagenomic datasets coming from virus-like particle enriched samples, we present and quantify the improvement of viral taxonomic assignment that is achievable with a new similarity-based approach. Indeed, prior to any use of similarity based taxonomic assignment methods, we propose assembling contigs from short reads as is currently routinely done in metagenomic studies, but then to further map unassembled reads to the assembled contigs. This additional mapping step increases significantly the proportions of taxonomically assignable sequence reads from a variety –plant, insect and environmental (estuary, lakes, soil, feces) – of virome studies.
Strokes related to intracranial aneurysm or arteriopathy have been reported in a few patients with late-onset Pompe disease. These reports suggested that cerebral vessel involvement could be an ...underrecognized complication of this disease.
We report cerebral artery involvement in three French patients with late-onset Pompe disease.
The first patient died at age 35 years from complications of a giant fusiform aneurysm of the basilar artery, and her 34-year-old sister showed evidence of dolichoectatic basilar artery on magnetic resonance angiography. A dilative arteriopathy complicated with carotid artery dissection was diagnosed in the third patient, aged 50 years. Two patients are currently being treated with enzyme replacement therapy (alglucosidase alfa), and regular angiographic follow-up showed the absence of progression of vascular abnormalities in one of them.
These observations, combined with previously reported cases, confirm that Pompe disease should be recognized as a predisposing condition to dilative arteriopathy and cerebral aneurysm formation, although the real incidence of these vascular complications remains unknown.
Mucopolysaccharidoses (MPS) often raise diagnostic challenges, particularly in patients with progressive disease and relatively non-specific signs and symptoms. Early diagnosis improves management ...and enables to start specific treatment when available. Each type of MPS is associated with a deficiency of a lysosomal enzyme which catalyses the degradation of glycosaminoglycans (GAGs). The initial diagnosis Wis suggested by quantifying and identifying the accumulated metabolites. Diagnosis is then confirmed by assaying the deficient enzyme, allowing diagnosis in a large majority of cases. Indirect markers, which do not arise directly from the deficient metabolic pathway and vary in concentration depending on the degree of disease progression, are used to support a diagnosis of MPS and/or monitor the efficacy of the specific treatment. Identifying the underlying genic abnormality enables family studies to be carried out and perform prenatal diagnosis.
Patients under 5years were not evaluated in the phase-3 study for enzyme replacement therapy (ERT) in MPS IV A. Here we describe the evolution of a severe Morquio A pediatric patient who was ...diagnosed at 19months old and treated by ERT at 21months old for the next 30months.
Applying the standard ERT protocol on this very young patient appeared to reduce his urinary excretion of glycosaminoglycans (GAGs); the improvements in both the 6minute-walk test (6MWT) and the stair climb test, however, were no different than those reported in the nature history study. Additionally, this young patient experienced many ERT-associated side effects, and as a result a specific corticosteroid protocol (1mg/kg of betamethasone the day before and 1h before the ERT infusion) was given to avoid adverse events. Under these treatments, the height of this patient increased during the first year of the ERT although no more height gain was observed thereafter for 18months. However, despite of ERT, his bone deformities (including severe pectus carinatum) actually worsened and his medullar cervical spine compression showed no improvement (thus needed decompression surgery).
Conclusion: early ERT treatment did not improve the bone outcome in this severe MPS IV A patient after the 30months-long treatment. A longer term follow up is required to further assess the efficacy of ERT on both the motor and the respiratory function of the patient.
Peripheral nerve system (PNS) involvement is common in Fabry's disease (FD), predominantly affecting the small nerve fibers that are difficult to investigate with conventional electrophysiological ...methods.
Eighteen patients followed for Fabry's disease underwent a prospective series of electroneurophysiological explorations, including a study of the cardiac parasympathetic autonomic nervous system (ANS) and electrochemical skin conductance (ESC) tests. Data were compared with those obtained in 18 matched healthy controls.
All patients had at least one clinical sign suggestive of neuropathy: 16 reported an acrosyndrome and 12 had dyshidrosis. Cold hypoesthesia was found in 15 patients and heat hypoesthesia in 13. Electroneurophysiological investigations and study of the cardiac parasympathetic ANS were normal in all patients. The ESC was significantly lower in FD patients compared with controls.
PNS involvement is common in FD and should be suspected in patients exhibiting an acrosyndrome, dyshidrosis and/or cold hypoesthesia. Conventional electrophysiological investigations are normal. New techniques, such as ESC, provide early diagnosis of small fiber involvement that currently requires more sophisticated tests difficult to apply in routine practice.
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