Tracy, Jennifer A.

AbstractMutations in glycogenin‐1 (GYG1) cause an adult‐onset polyglucosan body myopathy. We report here a patient presenting with late‐onset distal myopathy. We wish to highlight this rare clinical phenotype of GYG1‐related myopathy and the histological clues leading to its diagnosis.

ABSTRACTIntroductionOnion‐bulbs (OB) are concentrically layered Schwann‐cell processes, surrounding nerve fibers, occurring in both inherited and acquired demyelinating polyneuropathies. We investigated whether OB patterns (generalized, mixed, or focal) correlate with acquired or inherited neuropathies.MethodsOne hundred thirty‐one OB‐rich nerve biopsies were graded for OB pattern and inflammation without knowledge of clinical history. We classified inherited (n = 49) or acquired (n = 82) neuropathies based solely on clinical history.ResultsFifty‐one biopsies had generalized (34 inherited vs. 17 acquired, P < 0.001), 54 mixed (48 acquired vs. 6 inherited, P < 0.001), and 26 focal/multifocal (inherited [n = 9], acquired [n = 17]) OB. Inflammation occurred more frequently in acquired (n = 54) than inherited (n = 14) neuropathy (P = 0.004).DiscussionGeneralized OB correlates with inherited neuropathy; mixed OB with acquired. Inflammation occurs more in acquired neuropathy cases. OB patterns are best explained by ubiquitous Schwann‐cell involvement in inherited and multifocal Schwann‐cell involvement in acquired neuropathies and predict the electrophysiology of uniform demyelination in inherited and unequal demyelination in acquired neuropathies. Muscle Nerve 59:665–670, 2019

A 70-year-old female presented with a three-year history of evolving macroglossia causing dysphagia and dysarthria, with proximal muscle weakness. Given the classic physical finding of macroglossia, the patient underwent extensive evaluation for amyloidosis which proved to be negative apart from a bone marrow biopsy which stained positive for transthyretin without amino acid sequence abnormality, thus giving wild-type transthyretin amyloidosis. Since the wild-type transthyretin amyloidosis could not entirely explain her clinical presentation and evaluation, further studies were conducted in a sequential manner, thus leading to a diagnosis of Pompe disease explaining her presenting signs and symptoms including her macroglossia. Through this fascinating case, we attempt to highlight the approach for the diagnoses of two rare diseases in a patient by emphasizing the importance of having a broad differential diagnosis when presented with findings which may have been thought as pathognomonic for certain diseases.

ABSTRACTIntroduction: A calpain‐3 (CAPN3) gene heterozygous deletion (c.643_663del21) was recently linked to autosomal dominant (AD) limb‐girdle muscular dystrophy. However, the possibility of digenic disease was raised. We describe 3 families with AD calpainopathy carrying this isolated mutation. Methods: Probands heterozygous for CAPN3 c.643_663del21 were identified by targeted next generation or whole exome sequencing. Clinical findings were collected for probands and families. Calpain‐3 muscle Western blots were performed in 3 unrelated individuals. Results: Probands reported variable weakness in their 40s or 50s, with myalgia, back pain, or hyperlordosis. Pelvic girdle muscles were affected with adductor and hamstring sparing. Creatine kinase was normal to 1,800 U/L, independent of weakness severity. Imaging demonstrated lumbar paraspinal muscle atrophy. Electromyographic findings and muscle biopsies were normal to mildly myopathic. Muscle calpain‐3 expression was reduced. Discussion: This study provides further evidence for AD calpainopathy associated with CAPN3 c.643_663del21. No pathogenic variants in other genes known to cause myopathy were detected. Muscle Nerve 57: 679–683, 2018

ABSTRACTIntroduction: Autosomal dominant haploinsufficiency of GATA2 causes monocytopenia and natural killer cell lymphopenia, resulting in predisposition to mycobacterial, fungal, and viral infections. Methods: Herein we report on the clinical, serologic, electrophysiologic, and pathologic evaluations of a 29‐year‐old woman with GATA2 haploinsufficiency and active Epstein–Barr virus (EBV) infection complicated by subacute painful neuropathy. Results: Nerve conduction and electromyography studies showed predominantly demyelinating sensorimotor polyradiculoneuropathy. Lumbar spine MRI showed thickening and enhancement of the cauda equina nerve roots. Serum and cerebrospinal fluid anti‐IgG and IgM EBV capsid and nucleic acid antibodies were positive. Sural nerve biopsy showed microvasculitis and an increased frequency of fibers with segmental demyelination. Intravenous immunoglobulin and steroids improved the patient's neuropathy. Conclusion: GATA2 mutation–related immunodeficiency may predispose to EBV‐associated subacute demyelinating polyradiculoneuropathy by both viral susceptibility and immune dysregulation. In patients who present in this manner, immunodeficiency syndromes should be considered when lymphomatous infiltration is excluded. Immunotherapy can be helpful. Muscle Nerve 57: 150–156, 2018