Mutations in
GFPT1
(glutamine-fructose-6-phosphate transaminase 1), a gene encoding an enzyme involved in glycosylation of ubiquitous proteins, cause a limb-girdle congenital myasthenic syndrome ...(LG-CMS) with tubular aggregates (TAs) characterized predominantly by affection of the proximal skeletal muscles and presence of highly organized and remodeled sarcoplasmic tubules in patients’ muscle biopsies. We report here the first long-term clinical follow-up of 11 French individuals suffering from LG-CMS with TAs due to
GFPT1
mutations, of which nine are new. Our retrospective clinical evaluation stresses an evolution toward a myopathic weakness that occurs concomitantly to ineffectiveness of usual CMS treatments. Analysis of neuromuscular biopsies from three unrelated individuals demonstrates that the maintenance of neuromuscular junctions (NMJs) is dramatically impaired with loss of post-synaptic junctional folds and evidence of denervation–reinnervation processes affecting the three main NMJ components. Moreover, molecular analyses of the human muscle biopsies confirm glycosylation defects of proteins with reduced
O
-glycosylation and show reduced sialylation of transmembrane proteins in extra-junctional area. Altogether, these results pave the way for understanding the etiology of this rare neuromuscular disorder that may be considered as a “tubular aggregates myopathy with synaptopathy”.
ABSTRACT
Introduction: In young patients with mononeuropathy who lack family history and precipitating factors, hereditary neuropathy with liability to pressure palsy (HNPP) may be a possibility. Our ...objective is to propose neurophysiological criteria for HNPP in patients <30 years of age. Methods: We conducted a national multicenter retrospective clinical and neurophysiological study in patients under 30 with genetically confirmed HNPP. Results: All of the 51 patients included in the study had at least 1 demyelinating pattern in 2 asymptomatic nerves, and 3 abnormalities were found in almost 90%, including slowed motor nerve conduction velocity across the elbow in at least 1 ulnar nerve (97.5%), increased distal motor latency (DML) in at least 1 fibular nerve (95.8%), and increased DML in both median nerves (89%). Age influenced DML slightly only in the fibular nerve. Discussion: Dissemination of nerve involvement in HNPP incites to perform a complete nerve conduction study. including bilateral ulnar, fibular, and median nerves. Muscle Nerve 57: 217–221, 2018
Granulomatous myositis (GM) is a rare condition that has generally been described in association with sarcoidosis. In the absence of sarcoidosis or other underlying disease, a diagnosis of isolated ...GM is considered. Only one study has focused on the clinical difference between isolated GM and sarcoid myopathy (SM). We report 13 cases of symptomatic GM; 8 had sarcoidosis. All patients with sarcoidosis had predominantly proximal, symmetrical lower‐limb weakness, and 3 subsequently developed upper‐limb or distal involvement. Three of the five patients with isolated GM had predominantly distal muscle involvement, and two had dysphagia. Corticosteroid treatment was followed by prolonged improvement in only one patient with sarcoidosis. One patient had acute sarcoid myositis and benefited from methotrexate; other immunosuppressants and etanercept proved ineffective in chronic sarcoid myopathy. Three of the five patients with isolated GM responded to corticosteroid treatment. When last examined, three patients with sarcoidosis had severe disability, whereas patients with isolated GM showed milder weakness. Thus, SM was frequently associated with severe disability and rarely improved after corticosteroid treatment, whereas most patients with isolated GM improved. Muscle Nerve, 2006
Highlights • We retrospectively studied 131 French late onset Pompe disease patients (LOPD). • 4 patients needed pacemaker implantation for severe atrio-ventricular blocks. • In patients presenting ...with atrio-ventricular blocks, echocardiography was normal. • These patients had no risk factors for cardiovascular diseases. • Cardiac follow-up in PD patients should include periodic EKG and Holter-EKG monitoring.
Introduction
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a debilitating autoimmune neuropathy that is treated with intravenous immunoglobulin (IVIG). The aim of this ...retrospective study was to investigate the efficacy and safety of the sucrose-free IVIG Octagam® (Octapharma AG, Lachen, Switzerland) in patients with CIDP.
Methods
Data from 47 patients who received at least one dose of Octagam were collected from the records of 11 centres in France. Efficacy was assessed using Overall Neuropathy Limitation Scale (ONLS). Safety was evaluated using adverse event rates.
Results
Data from 24 patients who were IVIG naïve (
n
= 11) or had stopped IVIG ≥ 12 weeks before initiation of Octagam therapy (washout group;
n
= 13) were included in the efficacy analysis. At 4 months post-initiation of Octagam treatment, 41.7% of patients had improved their functional status (decrease of ≥ 1 ONLS score) with a significant change in the ONLS score from baseline (– 0.42;
p
= 0.04; signed test). Functional status was reduced in only two patients: one patient in the IVIG-naïve group and one patient in the IVIG-washout group. All 47 patients were included in the safety analysis, which showed that Octagam was well tolerated, with a frequency of 0.04 adverse events per Octagam course. The most common adverse drug reaction was headache.
Conclusions
These real-life results are consistent with the efficacy and safety of IVIG reported in randomised controlled studies. A long-term prospective study of Octagam in patients with CIDP is warranted.
Funding
Octapharma, France SAS.
Facioscapulohumeral muscular dystrophy type 1(FSHD1) is an autosomal dominant disorder associated with the contraction of D4Z4 less than 11 repeat units (RUs) on chromosome 4q35. Penetrance in the ...range of the largest alleles is poorly known. Our objective was to study the penetrance of FSHD1 in patients carrying alleles ranging between 6 to10 RUs and to evaluate the influence of sex, age, and several environmental factors on clinical expression of the disease.
A cross-sectional multicenter study was conducted in six French and one Swiss neuromuscular centers. 65 FSHD1 affected patients carrying a 4qA allele of 6-10 RUs were identified as index cases (IC) and their 119 at-risk relatives were included. The age of onset was recorded for IC only. Medical history, neurological examination and manual muscle testing were performed for each subject. Genetic testing determined the allele size (number of RUs) and the 4qA/4qB allelic variant. The clinical status of relatives was established blindly to their genetic testing results. The main outcome was the penetrance defined as the ratio between the number of clinically affected carriers and the total number of carriers.
Among the relatives, 59 carried the D4Z4 contraction. At the clinical level, 34 relatives carriers were clinically affected and 25 unaffected. Therefore, the calculated penetrance was 57% in the range of 6-10 RUs. Penetrance was estimated at 62% in the range of 6-8 RUs, and at 47% in the range of 9-10 RUs. Moreover, penetrance was lower in women than men. There was no effect of drugs, anesthesia, surgery or traumatisms on the penetrance.
Penetrance of FSHD1 is low for largest alleles in the range of 9-10 RUs, and lower in women than men. This is of crucial importance for genetic counseling and clinical management of patients and families.
Tangier disease (TD) (OMIM#205400) is a rare autosomal recessive disorder resulting from mutations in the
ABCA1
gene, leading to decreased levels of plasma high-density lipoproteins (HDL). Peripheral ...neuropathy is a common finding in this disease, and may present as relapsing/remitting mono/polyneuropathies or as syringomyelia-like neuropathy. We retrospectively analyzed four patients, and report here their clinical, biological, electrophysiological, imaging, and genetic findings. Three patients had a typical pseudosyringomyelic neuropathy including facial diplegia, but asymmetrical onset was observed in one patient who had first been misdiagnosed with Lewis–Sumner syndrome. Electrophysiological pattern was heterogeneous, showing both signs of demyelination and axonal degeneration. Truncating mutations of the
ABCA1
gene, including two previously undescribed mutations, were constantly found. Atypical symptom onset and demyelinating features on electrophysiological examination can be misleading in case of pseudosyringomyelic neuropathy. These reports illustrate two different neurological phenotypes in TD, namely the pseudosyringomyelic type and the Lewis–Sumner-like type, and advocate for a systematic assessment of lipid profile including HDL cholesterol in demyelinating neuropathies.
Les syndromes canalaires du membre supérieur sont fréquemment rencontrés en pratique électroneuromyographique, notamment dans l’exercice libéral. Il s’agit d’une atteinte tronculaire secondaire au ...passage du nerf dans une structure anatomique « contrainte » ; elle peut être révélée par un traumatisme ou maladie professionnelle. Le but de l’atelier est de savoir reconnaître les atteintes cliniques en lien avec un entrappement inhabituel et de réaliser l’exploration électrophysiologique appropriée. En neurographie on a recours soit une technique de “base” bien connue soit à une technique adaptée au tronc nerveux intéressé (exploration branche profonde du nerf ulnaire, technique bi-centimétrique, stimulation proximale, nerf sensitif inhabituel). Lors de l’examen myographique, il convient de savoir repérer des muscles inhabituels (long fléchisseur du pouce, carré pronateur, supra et infra-épineux, divers chefs du trapèze, …) en s’aidant dans certains cas de l’échographie musculaire.
The efficacy of intravenous immunoglobulins (IVIg) in patients with autoimmune diseases (AID) has been known for several decades. Majority of these patients received IVIg in hospital. A retrospective ...study was conducted in 22 centers in France to evaluate the feasibility of the administration of Tegeline, an IVIg from LFB Biomedicaments, and assess its safety at home, compared to in hospital, in patients with AID. The included patients were at least 18 years old, suffering from AID, and treated with at least 1 cycle of Tegeline at home after receiving 3 consecutive cycles of hospital-based treatment with Tegeline at a dose between 1 and 2 g/kg/cycle. Forty-six patients with AID, in most cases immune-mediated neuropathies, received a total of 138 cycles of Tegeline in hospital and then 323 at home. Forty-five drug-related adverse events occurred in 17 patients who received their cycles at home compared to 24 adverse events in hospital in 15 patients. Serious adverse events occurred in 3 patients during home treatment, but they were not life-threatening and did not lead to discontinuation of Tegeline. Forty-five patients continued their treatment with Tegeline at home or in hospital; 39 (84.8%) were still receiving home treatment at the end of the study. In conclusion, the study demonstrates the good safety profile of Tegeline administered at home at high doses in patients with AID who are eligible for home administration of Tegeline.
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