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The ultrastructure of peripheral nerve, motor end-plate and skeletal muscle in patients suffering from spinal muscular atrophy with respiratory distress type 1 (SMARD1)

Acta Neuropathologica volume 110, pages 289–297 (2005)Cite this article

Abstract

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is genetically and clinically distinct from classic spinal muscular atrophy (SMA1). It results from mutations in the gene encoding immunoglobulin μ-binding protein 2 (IGHMBP2) on chromosome 11q13. Patients develop distally pronounced muscular weakness and early involvement of the diaphragm, resulting in respiratory failure. Sensory and autonomic nerves are also affected at later stages of the disease. We investigated peripheral nerves, skeletal muscles and neuromuscular junctions (NMJ) ultrastructurally in five unrelated patients and three siblings with genetically confirmed SMARD1. In mixed motor and sensory nerves we detected Wallerian degeneration and axonal atrophy similar to the ultrastructural findings described in SMA1. Isolated axonal atrophy was evident in purely sensory nerves. All investigated NMJ of patients with SMARD1 were dysmorphic and lacked a terminal axon. Moreover, we also observed characteristics of neuropathies, such as abnormalities in myelination, that have not been described in spinal muscular atrophies so far. Based on these findings we conclude that impairment of IGHMBP2 function leads to axonal degeneration, abnormal myelin formation, and motor end-plate degeneration.

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Acknowledgments

This study was supported by grants from the Deutsche Forschungsgemeinschaft (HU 408/3–2) and from the Humboldt-University (2002–735). The authors wish to thank Marius Bartsch, Enrico Bertini, Lionel van Maldergem and Wolfgang Schlote for kindly providing the specimens, Hans H. Goebel, Angela Kaindl and Henning Schmalbruch for their critical comments and Catrin Janetzki and Hanna Plückhahn for their excellent technical assistance. Mutation analysis of SMN1 was performed by Sabine Rudnik-Schöneborn and Klaus Zerres.

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  1. Department of Paediatric Neurology, Charité, Medical Faculty, Humboldt University, Augustenburger Platz 1, 13353, Berlin, Germany

    Alexander Diers, Katja Grohmann & Christoph Hübner

  2. Institute of Neuropathology, Charité, Medical Faculty, Humboldt University, Berlin, Germany

    Marcel Kaczinski & Gisela Stoltenburg-Didinger

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  1. Alexander Diers
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  2. Marcel Kaczinski
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  3. Katja Grohmann
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  5. Gisela Stoltenburg-Didinger
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Correspondence to Alexander Diers.

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Diers, A., Kaczinski, M., Grohmann, K. et al. The ultrastructure of peripheral nerve, motor end-plate and skeletal muscle in patients suffering from spinal muscular atrophy with respiratory distress type 1 (SMARD1). Acta Neuropathol 110, 289–297 (2005). https://doi.org/10.1007/s00401-005-1056-y

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  • DOI: https://doi.org/10.1007/s00401-005-1056-y

Keywords

  • Spinal muscular atrophy with respiratory distress type 1
  • Spinal muscular atrophy with respiratory distress
  • Neuronopathy
  • Axonal atrophy
  • Wallerian degeneration