Anti-HMGCR myopathy may resemble limb-girdle muscular dystrophy

Payam Mohassel, Océane Landon-Cardinal, A. Reghan Foley, Sandra Donkervoort, Katherine S. Pak, Colleen Wahl, Robert T. Shebert, Amy Harper, Pierre Fequiere, Matthew Meriggioli, Camilo Toro, Daniel B Drachman, Yves Allenbach, Olivier Benveniste, Anthony Béhin, Bruno Eymard, Pascal Laforet, Tanya Stojkovic, Andrew L. Mammen, Carsten G. Bönnemann

Research output: Contribution to journalArticle

Abstract

Objective To determine the prevalence and clinical features of anti-HMGCR myopathy among patients with presumed limb-girdle muscular dystrophy (LGMD) in whom genetic testing has failed to elucidate causative mutations. Methods Patients with presumed LGMD and unrevealing genetic testing were selected based on a few clinico-pathologic features and tested for anti-HMGCR autoantibodies (n = 11). These clinico-pathologic features are peak creatine kinase (CK) greater than 1,000 IU/L and at least 3 of the following features: (1) limb-girdle pattern of weakness, (2) selective involvement of posterior thigh on clinical examination or muscle imaging, (3) dystrophic changes on muscle biopsy, and (4) no family history of muscular dystrophy. Results Six patients tested positive for anti-HMGCR autoantibodies. In 4, there was a presymptomatic phase, lasting as long as 10 years, characterized by elevated CK levels without weakness. Muscle biopsies revealed variable degrees of a dystrophic pathology without prominent inflammation. In an independent cohort of patients with anti-HMGCR myopathy, 17 of 51 (∼33%) patients were initially presumed to have a form of LGMD based on clinico-pathologic features but were ultimately found to have anti-HMGCR myopathy. Most of these patients responded favorably to immunomodulatory therapies, evidenced by reduction of CK levels and improved strength. Conclusions Anti-HMGCR myopathy can resemble LGMD. Diagnosis of patients with a LGMD-like presentation of anti-HMGCR myopathy is critical because these patients may respond favorably to immunotherapy, especially those with shorter disease duration.

Original languageEnglish (US)
Article numbere523
JournalNeurology: Neuroimmunology and NeuroInflammation
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2019

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Limb-Girdle Muscular Dystrophies
Muscular Diseases
Creatine Kinase
Genetic Testing
Muscles
Autoantibodies
Biopsy
Immunomodulation
Muscular Dystrophies
Thigh
Immunotherapy
Extremities
Pathology
Inflammation
Mutation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Mohassel, P., Landon-Cardinal, O., Foley, A. R., Donkervoort, S., Pak, K. S., Wahl, C., ... Bönnemann, C. G. (2019). Anti-HMGCR myopathy may resemble limb-girdle muscular dystrophy. Neurology: Neuroimmunology and NeuroInflammation, 6(1), [e523]. https://doi.org/10.1212/NXI.0000000000000523

Anti-HMGCR myopathy may resemble limb-girdle muscular dystrophy. / Mohassel, Payam; Landon-Cardinal, Océane; Foley, A. Reghan; Donkervoort, Sandra; Pak, Katherine S.; Wahl, Colleen; Shebert, Robert T.; Harper, Amy; Fequiere, Pierre; Meriggioli, Matthew; Toro, Camilo; Drachman, Daniel B; Allenbach, Yves; Benveniste, Olivier; Béhin, Anthony; Eymard, Bruno; Laforet, Pascal; Stojkovic, Tanya; Mammen, Andrew L.; Bönnemann, Carsten G.

In: Neurology: Neuroimmunology and NeuroInflammation, Vol. 6, No. 1, e523, 01.01.2019.

Research output: Contribution to journalArticle

Mohassel, P, Landon-Cardinal, O, Foley, AR, Donkervoort, S, Pak, KS, Wahl, C, Shebert, RT, Harper, A, Fequiere, P, Meriggioli, M, Toro, C, Drachman, DB, Allenbach, Y, Benveniste, O, Béhin, A, Eymard, B, Laforet, P, Stojkovic, T, Mammen, AL & Bönnemann, CG 2019, 'Anti-HMGCR myopathy may resemble limb-girdle muscular dystrophy', Neurology: Neuroimmunology and NeuroInflammation, vol. 6, no. 1, e523. https://doi.org/10.1212/NXI.0000000000000523
Mohassel P, Landon-Cardinal O, Foley AR, Donkervoort S, Pak KS, Wahl C et al. Anti-HMGCR myopathy may resemble limb-girdle muscular dystrophy. Neurology: Neuroimmunology and NeuroInflammation. 2019 Jan 1;6(1). e523. https://doi.org/10.1212/NXI.0000000000000523
Mohassel, Payam ; Landon-Cardinal, Océane ; Foley, A. Reghan ; Donkervoort, Sandra ; Pak, Katherine S. ; Wahl, Colleen ; Shebert, Robert T. ; Harper, Amy ; Fequiere, Pierre ; Meriggioli, Matthew ; Toro, Camilo ; Drachman, Daniel B ; Allenbach, Yves ; Benveniste, Olivier ; Béhin, Anthony ; Eymard, Bruno ; Laforet, Pascal ; Stojkovic, Tanya ; Mammen, Andrew L. ; Bönnemann, Carsten G. / Anti-HMGCR myopathy may resemble limb-girdle muscular dystrophy. In: Neurology: Neuroimmunology and NeuroInflammation. 2019 ; Vol. 6, No. 1.
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AU - Mohassel, Payam

AU - Landon-Cardinal, Océane

AU - Foley, A. Reghan

AU - Donkervoort, Sandra

AU - Pak, Katherine S.

AU - Wahl, Colleen

AU - Shebert, Robert T.

AU - Harper, Amy

AU - Fequiere, Pierre

AU - Meriggioli, Matthew

AU - Toro, Camilo

AU - Drachman, Daniel B

AU - Allenbach, Yves

AU - Benveniste, Olivier

AU - Béhin, Anthony

AU - Eymard, Bruno

AU - Laforet, Pascal

AU - Stojkovic, Tanya

AU - Mammen, Andrew L.

AU - Bönnemann, Carsten G.

PY - 2019/1/1

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N2 - Objective To determine the prevalence and clinical features of anti-HMGCR myopathy among patients with presumed limb-girdle muscular dystrophy (LGMD) in whom genetic testing has failed to elucidate causative mutations. Methods Patients with presumed LGMD and unrevealing genetic testing were selected based on a few clinico-pathologic features and tested for anti-HMGCR autoantibodies (n = 11). These clinico-pathologic features are peak creatine kinase (CK) greater than 1,000 IU/L and at least 3 of the following features: (1) limb-girdle pattern of weakness, (2) selective involvement of posterior thigh on clinical examination or muscle imaging, (3) dystrophic changes on muscle biopsy, and (4) no family history of muscular dystrophy. Results Six patients tested positive for anti-HMGCR autoantibodies. In 4, there was a presymptomatic phase, lasting as long as 10 years, characterized by elevated CK levels without weakness. Muscle biopsies revealed variable degrees of a dystrophic pathology without prominent inflammation. In an independent cohort of patients with anti-HMGCR myopathy, 17 of 51 (∼33%) patients were initially presumed to have a form of LGMD based on clinico-pathologic features but were ultimately found to have anti-HMGCR myopathy. Most of these patients responded favorably to immunomodulatory therapies, evidenced by reduction of CK levels and improved strength. Conclusions Anti-HMGCR myopathy can resemble LGMD. Diagnosis of patients with a LGMD-like presentation of anti-HMGCR myopathy is critical because these patients may respond favorably to immunotherapy, especially those with shorter disease duration.

AB - Objective To determine the prevalence and clinical features of anti-HMGCR myopathy among patients with presumed limb-girdle muscular dystrophy (LGMD) in whom genetic testing has failed to elucidate causative mutations. Methods Patients with presumed LGMD and unrevealing genetic testing were selected based on a few clinico-pathologic features and tested for anti-HMGCR autoantibodies (n = 11). These clinico-pathologic features are peak creatine kinase (CK) greater than 1,000 IU/L and at least 3 of the following features: (1) limb-girdle pattern of weakness, (2) selective involvement of posterior thigh on clinical examination or muscle imaging, (3) dystrophic changes on muscle biopsy, and (4) no family history of muscular dystrophy. Results Six patients tested positive for anti-HMGCR autoantibodies. In 4, there was a presymptomatic phase, lasting as long as 10 years, characterized by elevated CK levels without weakness. Muscle biopsies revealed variable degrees of a dystrophic pathology without prominent inflammation. In an independent cohort of patients with anti-HMGCR myopathy, 17 of 51 (∼33%) patients were initially presumed to have a form of LGMD based on clinico-pathologic features but were ultimately found to have anti-HMGCR myopathy. Most of these patients responded favorably to immunomodulatory therapies, evidenced by reduction of CK levels and improved strength. Conclusions Anti-HMGCR myopathy can resemble LGMD. Diagnosis of patients with a LGMD-like presentation of anti-HMGCR myopathy is critical because these patients may respond favorably to immunotherapy, especially those with shorter disease duration.

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