Downloaded from http://jnnp.bmj.com/ on November 26, 2014 - Published by group.bmj.com ABN Abstracts genes have been implicated in causing the inherited neuropathies, and many more remain unknown. In order to determine the proportion of patients with inherited neuropathy attending our clinic who obtained a genetic diagnosis, we screened all known genes that cause CMT, HMN and HSAN. Of 871 patients attending a specialist neuropathy clinic over a 5-year period, 613 had an inherited neuropathy of whom 409 had CMT. A genetic diagnosis was reached in 59% of patients with CMT; 54% accounted for by chromosome 17 rearrangements or mutations in the commonly available genes PMP22, GJB1, MPZ and MFN2. A genetic diagnosis was achieved in 79% of patients with CMT1 and 35% of CMT2. The chromosome 17 duplication only accounted for 38% of CMT, less than reported in other populations; this reﬂects a bias in our clinic towards patients with rarer forms of CMT. We give details of the individual contributions the rarer genes made to our cohort. These results suggest that the majority of patients with CMT1 should obtain a genetic diagnosis. Mutations in the rarer known genes account for a small proportion of patients with CMT, and many genes for CMT2 remain unknown. We suggest an algorithm for genetic testing in patients with CMT in the UK. Email: [email protected] Alexandrovska, Bulgaria; UCL Institute of Child Health, UK; Univeristy of Oxford, UK; Ludwig Maximillians University, Germany We report on the clinical features of a distinct group of DOK 7 negative limb girdle congenital myasthenic syndrome (LG-CMS), the cause of which has only recently been unravelled. Congenital myasthenic syndromes are a rare group of inherited neuromuscular disorders associated with distinct clinical and genetic abnormalities, in which neuromuscular transmission is impaired. An interesting and often difﬁcult group to recognise is the LG-CMS. This typically manifests with shoulder and pelvic girdle muscle weakness with or without additional features including ocular and bulbar involvement. Until recently, DOK 7 gene mutations have been the only recognised genetic cause of this phenotype and were found in half of all LG-CMS patients. Mutations in a novel CMS gene (GFPT1) were recently implicated in an undiagnosed, DOK 7 negative, LG-CMS cohort of 24 patients. All patients had proximal limb weakness with no ocular or bulbar features and showed a positive response to pyridostigmine. Although age of onset of disease was usually in early childhood, a great number of patients presented to medical attention well into adulthood. Furthermore, tubular aggregates arising from the sarcoplasmic reticulum were seen in the majority of patients. Email: [email protected] 1042 HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY TYPE 1: CORRELATION OF SEVERITY AND PLASMA ATYPICAL DEOXY-SPHYNGOID BASES 1118 ARE MND PATIENTS PRE-MORBIDLY FITTER? INDIRECT EVIDENCE FROM HOSPITAL RECORD-LINKAGE doi:10.1136/jnnp-2011-301993.16 L Matilde, F Eichler, T Hornemann, S M Murphy, J Polke, K Bull, H Houlden, M M Reilly. MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, UK; Massachusetts General Hospital/Harvard Medical School, USA; Institute for Clinical Chemistry, University Hospital Zurich, Switzerland; Neurogenetics Unit, National Hospital for Neurology and Neurosurgery, UK Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is an inherited peripheral neuropathy characterised by marked sensory loss, variable motor involvement and frequent complications. Mutations in the SPTLC1 gene are responsible for this disorder. Mutant SPTLC1 is associated with the accumulation of two atypical deoxy-sphyngoid bases (dSBs) which produce a toxic effect in cultured sensory neurons. dSB levels are elevated in plasma of patients with HSAN1 and transgenic mice. L-serine is a potential therapy for HSAN1, however the lack of natural history studies and outcome measures are major barriers to a clinical trial. This crosssectional study has been conducted to fully characterise the phenotype of HSAN1 and to establish correlation of plasma dSBs with disease severity. We obtained detailed clinical data in a cohort of 20 SPTLC1/ HSAN1 patients. Clinical impairment was assessed by the Charcot Marie Tooth Neuropathy score (CMTNS). Onset occurred in the second and third decade in the majority of patients. Males showed a more severe disease course compared to females. Neuropathic pain was present in 70% of patients. Sensory complications were observed in 80% of patients. dSBs were signiﬁcantly elevated in all patients and correlate with disease severity. This cross-sectional study highlights the role of dSBs as a potential marker for disease severity. A longitudinal study to establish whether dSBs can be used as biomarker of progression of disease is warranted. Email: [email protected] doi:10.1136/jnnp-2011-301993.18 M Turner, C Wotton, K Talbot, M J Goldacre. Oxford University, UK Background Case-control studies to identify risk factors for MND suffer from the intractable problem of recall bias, and have provided conﬂicting results. There is a persistent anecdotal observation that MND patients arise from a ‘ﬁtter’ population. Such a physical proﬁle might then be reﬂected in a reduced incidence of coronary heart disease (CHD) prior to the development of MND. Methods A record-linkage study of a large national database of hospital admissions was undertaken. The ratio of the rate of MND in people without a record of CHD, to the rate in people with a record of CHD was calculated, factoring out premature death in the non-CHD and CHD cohorts. Similar analysis for Parkinson’s disease (PD) and multiple sclerosis (MS) was undertaken. Results Those without a record of CHD were at higher risk of ALS than those with CHD (rate ratio 1.14; 95% CI 1.05 to 1.22). The higher risk was not found for PD (0.95; 95% CI 0.93 to 0.98) or MS (0.95; 95% CI 0.88 to 1.04). Discussion This study provides indirect support for the assertion that MND arises in a cardiovascularly ﬁtter population. It has been proposed that greater physical activity might trigger MND, perhaps through oxidative stress. An alternative formulation might be that ﬁtness in part reﬂects a distinct motor system architecture which, whilst associated with improved physical performance in youth, may be inherently vulnerable to the stochastic events of ageing. Email: [email protected] 1130 CLINICAL FEATURES AND CLINICAL COURSE OF SPORADIC INCLUSION BODY MYOSITIS (IBM): A PROSPECTIVE COHORT STUDY: IBM-NET doi:10.1136/jnnp-2011-301993.19 1106 THE CLINICAL PHENOTYPIC SPECTRUM OF GFPT1 ASSOCIATED CONGENITAL MYASTHENIC SYNDROME doi:10.1136/jnnp-2011-301993.17 A Cortese, P Machado, A Miller, S Brady, D Hilton-Jones, J Morrow, A Hiscock, E Dewar, M Parton, M Hanna. MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, UK; Oxford Muscle and Nerve Centre, John Radcliffe Hospital, Oxford, UK A Chaouch, J S Mueller, V Guergueltcheva, F Muntoni, K Bushby, V Straub, J Palace, D Beeson, A Abicht, H Lochmuller. University of Newcastle, University Hospital Objective To assess the clinical features and clinical course of sporadic Inclusion body myositis (sIBM) in a prospective cohort of J Neurol Neurosurg Psychiatry March 2012 Vol 83 No 3 5 of 27 Downloaded from http://jnnp.bmj.com/ on November 26, 2014 - Published by group.bmj.com 1106 The clinical phenotypic spectrum of GFPT1 associated congenital myasthenic syndrome A Chaouch, J S Mueller, V Guergueltcheva, F Muntoni, K Bushby, V Straub, J Palace, D Beeson, A Abicht and H Lochmuller J Neurol Neurosurg Psychiatry 2012 83: e1 doi: 10.1136/jnnp-2011-301993.17 Updated information and services can be found at: http://jnnp.bmj.com/content/83/3/e1.79 Email alerting service Topic Collections Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article. 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