[McArdle's disease revealed by acute low back pain]. / Une maladie de McArdle révélée par une lombalgie aiguë.

INTRODUCTION: McArdle disease, or glycogen storage disease type V (GSD 5), is a rare metabolic myopathy linked to an autosomal recessive myophosphorylase deficiency. CASE REPORT: 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. DISCUSSION: 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.

Long term disease burden post-transplantation: three decades of observations in 25 Hurler patients successfully treated with hematopoietic stem cell transplantation (HSCT).

BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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.

Weighing in on the risks and benefits of probiotic use in HIV-infected and immunocompromised populations.

Probiotics are used in the prophylaxis and treatment of several conditions, including irritable bowel syndrome, diarrhoea, necrotising enterocolitis (NEC) and colic in infants. Despite the long history of probiotic use in humans, there is still significant debate about their efficacy and safety, particularly in HIV-infected and immunocompromised individuals. Here, we reviewed the safety and adverse event (AE) reporting from clinical trials that have tested probiotics in at risk populations, including HIV-infected individuals, the terminally ill and elderly, and neonates. Our analysis suggests that the benefits of probiotic therapy outweigh their potential risks in HIV-infected populations, and in the treatment of colic and NEC in low birth weight or premature neonates. Most case reports of severe AEs were in the elderly and terminally ill, or in those with additional severe medical conditions. We conclude that probiotic use, as adjunctive treatment, is effective and safe in the majority of patients including HIV-infected individuals, although special care should be taken in individuals with extreme immunosuppression and severe medical conditions in all ages.

Increase in taxonomic assignment efficiency of viral reads in metagenomic studies.

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 ¼ 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.

Peripheral nerve involvement in Fabry's disease: Which investigations? A case series and review of the literature.

BACKGROUND: 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. PATIENTS AND 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. RESULTS: 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. CONCLUSION: 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.

Clinical Analysis of Algerian Patients with Pompe Disease.

Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha-glucosidase (GAA), also called acid maltase, an enzyme that degrades lysosomal glycogen. The clinical presentation of Pompe's disease is variable with respect to the age of onset and rate of disease progression. Patients with onset of symptoms in early infancy (infantile-onset Pompe disease (IOPD)) typically exhibit rapidly progressive hypertrophic cardiomyopathy and marked muscle weakness. Most of them die within the first year of life from cardiac and/or respiratory failure. In the majority of cases of Pompe's disease, onset of symptoms occurs after infancy, ranging widely from the first to sixth decade of life (late-onset Pompe's disease or LOPD). Progression of the disease is relentless and patients eventually progress to loss of ambulation and death due to respiratory failure. The objective of this study was to characterize the clinical presentation of 6 patients (3 with EOPD and the other 3 with LOPD) of 5 families from the East of Algeria. All our patients were diagnosed as having Pompe's disease based on biochemical confirmations of GAA deficiency by dried blood spots (DBS) and GAA gene mutations were analyzed in all patients who consented (n = 4). Our results are similar to other ethnic groups.

[Acid sphingomyelinase deficiency (Niemann-Pick disease type B) in adulthood: A retrospective multicentric study of 28 adult cases]. / Déficit en sphingomyélinase acide (maladie de Niemann-Pick B) : une étude rétrospective multicentrique de 28 patients adultes.

INTRODUCTION: Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease with a clinical spectrum ranging from a neurovisceral infantile form (Niemann-Pick disease type A) to a chronic visceral form also encountered in adults (Niemann-Pick disease type B, NP-B). METHODS: Retrospective multicentric analysis of French adult patients with ASMD over the period 1985-March 2015. Clinical, biological, and imaging data were analyzed. RESULTS: Twenty-eight patients (19 males, 9 females) were analyzed. Diagnosis was made before the age of 10 years in 16 cases. Main symptoms at diagnosis were spleen/liver enlargement and interstitial lung disease. Biological abnormalities included: thrombocytopenia (platelet count <150 000/mm3) in 24 cases including 4 patients with platelet count <60 000/mm3, constantly low high-density lipoprotein (HDL) cholesterol, polyclonal hypergammaglobulinemia (n=6), monoclonal gammopathy of unknown significance (n=5), normal prothrombin level discordant with low factor V (n=5), elevated chitotriosidase level (n=11). The diagnosis was confirmed in all cases by deficient acid sphingomyelinase enzyme activity. SMPD1 gene sequencing was performed in 25 cases. The frequent p.R610del mutation was largely predominant, constituting 62% of the non-related alleles. During the follow-up period, three patients died before 50 years of age from cirrhosis, heart failure and lung insufficiency, respectively. CONCLUSION: ASMD in adulthood (NP-B) associates spleen/liver enlargement and interstitial lung disease. Early diagnosis and appropriate management are essential for reducing the risk of complications, improving quality of life, and avoiding inappropriate procedures such as splenectomy. To date, only symptomatic therapy is available. A phase 2/3 therapeutic trial with IV infusion of recombinant enzyme is on-going.

30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: About one case.

Patients under 5 years 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 19 months old and treated by ERT at 21 months old for the next 30 months. Applying the standard ERT protocol on this very young patient appeared to reduce his urinary excretion of glycosaminoglycans (GAGs); the improvements in both the 6 minute-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 (1 mg/kg of betamethasone the day before and 1 h 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 18 months. 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 30 months-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.

Discovery of parvovirus-related sequences in an unexpected broad range of animals.

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.

A Novel Itera-Like Densovirus Isolated by Viral Metagenomics from the Sea Barley Hordeum marinum.

Densoviruses (DVs) infect arthropods and belong to the Parvoviridae family. Here, we report the complete coding sequence of a novel DV isolated from the plant Hordeum marinum (Poaceae) by viral metagenomics, and we confirmed reamplification by PCR. Phylogenetic analyses showed that this novel DV is related to the genus Iteradensovirus.

[Laboratory diagnosis and follow up of mucopolysaccharidoses]. / Diagnostic et suivi des mucopolysaccharidoses.

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.

[Prenatal symptoms and diagnosis of inherited metabolic diseases]. / Maladies héréditaires du métabolisme : signes anténatals et diagnostic biologique.

Inherited metabolic diseases are mostly due to enzyme deficiency in one of numerous metabolic pathways, leading to absence of a compound downstream from and the accumulation of a compound upstream from the deficient metabolite(s). Diseases of intoxication by proteins (aminoacidopathies, organic acidurias, urea cycle defects) and by sugars (galactosemia, fructosemia) usually do not give prenatal symptoms since mothers protect their fetuses from pathological metabolite accumulation. A well-known exception is hypoplasia of corpus callosum, as is sometimes observed in nonketotic hyperglycinemia and sulfite oxidase deficiency. Conversely, women with phenylketonuria "poison" their fetus if they are not treated (spontaneous abortions, intrauterine growth restriction [IUGR], cardiac malformations, and brain disease). Amino acid synthesis defects can lead to prenatal symptoms: microcephaly in serine deficiency (detectable by amino acid analysis in fetal cord blood), and brain malformations in glutamine synthetase deficiency. Impaired folate metabolism is involved in a large fraction of neurodevelopmental defects referred to as spina bifida, yet the underlying genetic component(s) are largely unknown. Energy metabolism diseases caused by defects in the synthesis or utilization of relevant metabolites lead to organ dysfunctions or malformations, but prenatal diagnosis is usually impossible unless genetic analysis can rely on a previously affected child in the family. A somewhat intermediate condition is defects of mitochondrial beta-oxidation of fatty acids, as they may sometimes be symptomatic prenatally (notably the HELLP syndrome or other presentations), and in this case, organic acid and acylcarnitine analysis in amniotic fluid can be informative in the absence of an index case. In contrast, complex molecule diseases commonly give prenatal symptoms that may permit the diagnosis even in the absence of index cases: hydrops fetalis and skeletal anomalies in lysosomal storage diseases, hydrops fetalis in congenital disorders of glycosylation (CDG) and transaldolase deficiency, brain malformations in O-glycosylation defects, brain malformations, kidney cysts and skeletal anomalies in peroxysomal diseases (Zellweger syndrome), syndactyly, genitalia malformations, and IUGR in Smith-Lemli-Opitz (SLO) syndrome. Although many metabolic disorders show biochemical abnormalities during fetal development that are informative for prenatal diagnosis, only a fraction of them are clinically/sonographically symptomatic before birth, thus allowing for prenatal diagnosis in the absence of an index case, i.e., serine deficiency, some fatty acid beta-oxidation defects, transaldolase deficiency, lysosomal diseases, CDG, Zellweger syndrome, and SLO syndrome.

The virulence-transmission trade-off in vector-borne plant viruses: a review of (non-)existing studies.

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.

[Priapism: a severe paediatric complication of Fabry disease]. / Le priapisme: une complication pédiatrique grave de la maladie de Fabry.

Fabry disease is an X-linked recessive lysosomal storage disorder caused by α-galactosidase A deficiency. Although the disease presents in childhood, diagnosis is often delayed to adulthood or missed, presumably due to the lack of specificity of the symptoms and to the absence of major complication during the paediatric years. We report a 9-year-old boy known to have a Fabry disease who presented an episode of priapism. Successful treatment was achieved by repeated corporeal aspiration under general anaesthesia. This case is the fifth report of priapism in children with Fabry disease, suggesting that priapism may be a severe vascular complication of the disease during infancy. This report emphasizes the importance of an early diagnosis and treatment of Fabry disease, including enzyme replacement therapy, to prevent major disease-associated morbidity and to optimize patient outcomes.

[Contribution of the measurement of globotriaosylceramide in urine to the diagnosis and follow-up of Fabry disease]. / Intérêt du dosage du globotriaosylcéramide urinaire pour le diagnostic et le suivi du traitement de la maladie de Fabry.

Globotriaosylceramide (Gb(3)) has been measured in urine of 35 male hemizygotes and 66 female heterozygotes for Fabry disease (FD). In males, Gb(3) measurement allows to confirm the diagnosis which is based on deficient α-galactosidase A (α-Gal A) activity in leukocytes. Our results show that hemizygotes for classic FD have increased Gb(3) and C24/C18 isoforms ratio. Hemizygotes for FD variants have slightly elevated or normal Gb(3) and/or C24/C18 ratio. These variants often have a residual α-Gal A activity, and milder clinical signs. In females, urinary Gb(3) is more informative than α-Gal A activity in leukocytes. Our study shows that urinary Gb(3) (measurement and C24/C18 ratio) allows the diagnosis of 92 % of classical FD heterozygotes, and is often normal in variant FD heterozygotes. The diagnosis of FD heterozygote cannot be completely excluded even if urinary Gb(3) and α-Gal A in leukocytes are normal. Urinary Gb(3) can be used for therapeutic follow-up (enzyme replacement therapy) when increased.

[Contribution of genotyping in Fabry's disease]. / Apports du génotypage dans la maladie de Fabry.

Fabry's disease is an X-linked disorder due to mutations in the GLA gene encoding the lysosomal enzyme alpha-galactosidase A. Clinically, most patients present with the "classical" form, though "variant" forms with inaugural or preminent heart or kidney involvement have been described. Heterozygous women are most often symptomatic though generally less severely affected than men. We performed mutation analysis in 170 patients from 65 families and identified 55 different mutations. Our results confirm the wide molecular heterogeneity at this locus. Molecular study allows to confirm the diagnosis in male patients and the reliable diagnosis of heterozygous females in the family as biochemical tests (alpha-galactosidase A activity and urinary Gb(3) study) can be normal. However, in a few cases in which the index case is a female, it may remain difficult in the absence of an extensive familial study, to confirm (identification of a new missense the pathogenicity of which is unknown) or rule out (no gene alteration found) an heterozygote. Generally, genotype/phenotype correlations remain difficult as only a few mutations are more frequent. Furthermore, variations of the phenotype, even within the same family, suggest that other factors (genetic and epigenetic) could influence disease progression.

Aseptic meningitis and ischaemic stroke in Fabry disease.

BACKGROUND: Fabry disease (OMIM 301 500) is an X-linked lysosomal storage disease. Neurological symptoms in Fabry disease mainly include stroke, acroparesthesia, cranial nerve palsies and autonomic dysfunction. We report on aseptic meningitis in Fabry patients. METHODS: Clinical analysis, brain magnetic resonance imaging, cerebrospinal fluid analysis, treatment and outcome data were analysed in three cases of meningitis associated with Fabry disease. FINDINGS: Mean age at meningitis onset was 26.6 (24-28) years. Headache was present in all cases and fever in two cases. Meningitis was always diagnosed before Fabry disease. A familial history of Fabry disease was present in two cases. Non-neurological symptoms caused by Fabry disease were present in all cases. All patients also suffered stroke and sensorineural hearing loss. Cerebrospinal fluid (CSF) analysis showed pleocytosis (mean, 36; range: 8-76 cells/mm(3)) and a high protein level (mean, 63; range, 47-70 mg/dl). C-reactive protein blood levels and erythrocyte sedimentation rate were raised. Diagnosis was assessed by low alpha-galactosidase A dosage and/or gene mutation analysis in all cases. All patients were treated with enzyme replacement therapy (ERT). In two cases, lumbar puncture was repeatedly performed and there was no normalisation of CSF under ERT alone, at 9 and 24 months of follow-up, respectively. One patient who suffered intracranial hypertension was treated efficiently with steroids, associated with azathioprine. The fact that Fabry disease could be an auto-inflammatory disorder is discussed. INTERPRETATION: Fabry disease may cause aseptic meningitis.

Four successful pregnancies in a patient with mucopolysaccharidosis type I treated by allogeneic bone marrow transplantation.

To date, little is known about the fertility of women suffering from mucopolysaccharidosis type I (MPS I). We report on a female patient with MPS I treated by allogeneic bone marrow transplantation (BMT) at the age of 4 years (after a conditioning regimen containing busulfan 16 mg/kg and cyclophosphamide 100 mg/kg) who had four successful pregnancies without any reproductive assistance. Clinical and biological examinations of the children were normal. On the basis of this case, we discuss the fertility counselling of female MPS I patients at the time of BMT.

[Enzyme replacement therapy in a boy with infantile Pompe disease: cardiac follow-up]. / Enzymothérapie substitutive chez un nourrisson atteint de maladie de Pompe : évolution cardiologique.

Pompe disease is an autosomal recessive glycogen storage disorder caused by acid-alpha-glucosidase deficiency. The infantile form is usually fatal by 1 year of age in the absence of specific therapy. We report the cardiac follow-up of a 4-month-old boy treated with enzyme replacement therapy (ERT) for 8 months. The patient had no cardiac failure at the age of 1 year. Before starting ERT, ECG showed a shortened PR interval, with huge QRS complexes and biventricular hypertrophy; echocardiography demonstrated major hypertrophic cardiomyopathy. The QRS voltage (SV1+RV6) decreased from 13 to 2.9 mV after 32 weeks of ERT, suggesting a progressive reduction of cardiac hypertrophy and intracellular glycogen excess. The PR interval increased from 60 to 90 ms. A block of the right bundle branch appeared after 13 weeks of treatment. The indexed left ventricular mass decreased from 240 to 90 g/m2 after 30 weeks of ERT. The left ventricular ejection fraction decreased transitorily between the 5th and the 15 th weeks of treatment. In summary, ERT is an efficient therapeutic approach for the cardiomyopathy of infantile Pompe disease. However, the possible occurrence of a right bundle branch block and a transitory alteration in the ejection fraction highlight the importance of cardiac follow-up.

Dilative arteriopathy and basilar artery dolichoectasia complicating late-onset Pompe disease.

BACKGROUND: 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. METHODS: We report cerebral artery involvement in three French patients with late-onset Pompe disease. RESULTS: 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. CONCLUSION: 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.