Branching Enzyme Deficiency: Expanding The Clinical Spectrum (P6.108)

OBJECTIVE:Our aim is to describe the clinical presentation and progression of a new intermediate variant of glycogen branching enzyme (GBE) deficiency, and to discuss genotype:phenotype correlations. BACKGROUND: The neuromuscular presentation of GBE deficiency includes a severe infantile form and a late-onset variant known as adult polyglucosan body disease (APBD). Here, we describe two patients with adult acute onset of fluctuating neurological signs and brain magnetic resonance (MRI) lesions simulating multiple sclerosis (MS). A better definition of this new clinical entity is needed to facilitate diagnosis. DESIGN/METHODS:We followed during 7 years two non-Ashkenazi patients with adult and acute onset of neurological signs. We obtained repeat brain MRIs, performed muscle and nerve biopsies, and studied GBE at the biochemical and molecular levels. RESULTS:Molecular analysis showed that one patient was compound heterozygous (c.1544G˃A, c.1961-1962delCA) and the other homozygous (c.1544G˃A) for GBE1 mutations. Residual GBE activity was 16 and 30 % of normal in leukocytes. Both patients presented acute episodes of transient neurological symptoms and, at 45 and 53 years of age, neurological impairment was mild. Brain MRI revealed relatively non-progressive white-matter lesions and spinocerebellar atrophy similar to typical APBD. CONCLUSIONS:GBE1 mutations can cause an early adult onset relapsing-remitting form of polyglucosan body disease distinct from APBD in several ways: (i) younger age at onset; (ii) subacute and remitting course simulating MS; and (iii) history of infantile liver involvement. This should orient neurologists towards the correct diagnosis. Study Supported by: none Disclosure: Dr. Paradas has nothing to disclose. Dr. Akman has nothing to disclose. Dr. Ionete has received personal compensation for activities with Bayer Pharmaceuticals Corp., Teva Neuroscience, Serono Inc., and Biogen Idec. Dr. Lau has nothing to disclose. Dr. Riskind has received personal compensation for activities with EMD Serono, Questcor Pharmaceuticals, and Biogen Idec as a consultant, and with Teva Neuroscience as a speaker. Dr. Riskind has received research support from Biogen Idec, Teva Neuroscience, Hoffman-LaRoche, Genentech Inc., and Novartis. Dr. Jones has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Hirano has received personal compensation for activities with Athena Diagnostics. Dr. Hirano has received personal compensation in an editorial capacity for Current Neurology and Neuroscience Reports. Dr. Hirano has received research support from Santhera Pharmaceutical, Pfizer Inc, and Edison Pharmaceuticals. Dr. DiMauro has received personal compensation in an editorial capacity for MedLink Neurology.