title: Muscle Pathology as a Diagnostic Clue to Allgrove Syndrome.
abstract: Allgrove or triple A syndrome is a rare autosomal recessive disorder that can present with a variable range of multi-system manifestations, including optic atrophy, cerebellar ataxia, upper and lower motoneuron signs and various neuropathic abnormalities. These cases are a diagnostic challenge, particularly when the eponymous combination of achalasia, Addisonianism and alacrima is incomplete. Therefore, it is in the differential diagnosis for multisystem conditions and should be known to pathologists who diagnose disorders of skeletal muscle. Here, we describe new findings in skeletal muscle histology from the case of a boy of consanguineous Turkish origin whose achalasia provided the only specific clinical clue to the diagnosis. These include myocyte nuclear abnormalities with partially abnormal anti-lamin A/C immunohistochemistry and altered nuclear ultrastructure but without overt abnormalities of nuclear pore morphology. In this case, the condition was associated with a hitherto unreported c.762delC mutation in the nucleoporin gene AAAS.
authors.affiliation: From Muscle Lab, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany (JR, KT), Institute of Clinical Genetics, Bonn, Germany (NK), Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany (JW, AR), Department of Neuropathology, University of Bonn Medical Centre, Bonn, Germany (KK), Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V, Department of Bioanalytics, Tissue Omics group, Dortmund, Germany (AR), John Walton Muscular Dystrophy Research Centre (JWMDRC), Newcastle University, International Centre for Life, Central Parkway, UK, Newcastle upon Tyne (AR).
authors.forename: Jens
authors.initials: J
authors.lastname: Reimann
authors.affiliation: From Muscle Lab, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany (JR, KT), Institute of Clinical Genetics, Bonn, Germany (NK), Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany (JW, AR), Department of Neuropathology, University of Bonn Medical Centre, Bonn, Germany (KK), Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V, Department of Bioanalytics, Tissue Omics group, Dortmund, Germany (AR), John Walton Muscular Dystrophy Research Centre (JWMDRC), Newcastle University, International Centre for Life, Central Parkway, UK, Newcastle upon Tyne (AR).
authors.forename: Nicolai
authors.initials: N
authors.lastname: Kohlschmidt
authors.affiliation: From Muscle Lab, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany (JR, KT), Institute of Clinical Genetics, Bonn, Germany (NK), Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany (JW, AR), Department of Neuropathology, University of Bonn Medical Centre, Bonn, Germany (KK), Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V, Department of Bioanalytics, Tissue Omics group, Dortmund, Germany (AR), John Walton Muscular Dystrophy Research Centre (JWMDRC), Newcastle University, International Centre for Life, Central Parkway, UK, Newcastle upon Tyne (AR).
authors.forename: Karen
authors.initials: K
authors.lastname: Tolksdorf
authors.affiliation: From Muscle Lab, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany (JR, KT), Institute of Clinical Genetics, Bonn, Germany (NK), Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany (JW, AR), Department of Neuropathology, University of Bonn Medical Centre, Bonn, Germany (KK), Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V, Department of Bioanalytics, Tissue Omics group, Dortmund, Germany (AR), John Walton Muscular Dystrophy Research Centre (JWMDRC), Newcastle University, International Centre for Life, Central Parkway, UK, Newcastle upon Tyne (AR).
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.affiliation: From Muscle Lab, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany (JR, KT), Institute of Clinical Genetics, Bonn, Germany (NK), Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany (JW, AR), Department of Neuropathology, University of Bonn Medical Centre, Bonn, Germany (KK), Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V, Department of Bioanalytics, Tissue Omics group, Dortmund, Germany (AR), John Walton Muscular Dystrophy Research Centre (JWMDRC), Newcastle University, International Centre for Life, Central Parkway, UK, Newcastle upon Tyne (AR).
authors.forename: Klaus
authors.initials: K
authors.lastname: Kuchelmeister
authors.affiliation: From Muscle Lab, Department of Neurology, University of Bonn Medical Centre, Bonn, Germany (JR, KT), Institute of Clinical Genetics, Bonn, Germany (NK), Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany (JW, AR), Department of Neuropathology, University of Bonn Medical Centre, Bonn, Germany (KK), Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V, Department of Bioanalytics, Tissue Omics group, Dortmund, Germany (AR), John Walton Muscular Dystrophy Research Centre (JWMDRC), Newcastle University, International Centre for Life, Central Parkway, UK, Newcastle upon Tyne (AR).
authors.forename: Andreas
authors.initials: A
authors.lastname: Roos
mesh_terms: D000309:Adrenal Insufficiency / Q000175:diagnosis* / Q000473:pathology*; D002467:Cell Nucleus / Q000473:pathology; D002648:Child; D003241:Consanguinity; D003937:Diagnosis, Differential; D004931:Esophageal Achalasia / Q000175:diagnosis* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D032342:Muscle Cells / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D028861:Nuclear Pore Complex Proteins / Q000235:genetics
chemical_list: C416506:AAAS protein, human; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins
keywords: Achalasia; Allgrove syndrome; Nuclear pathology; Nuclear pore; Skeletal muscle; Triple A syndrome