Adult Spinal Muscular Atrophy

Adult spinal muscular atrophy is a genetic neurodegenerative disorder characterized by muscle wasting and weakness. In adults, normal life expectancy is achieved, as only mild weakness may be encountered. The diagnosis rests on confirming genetic mutations.

This disorder is caused by the following process: hereditary.

Presentation

Adult spinal muscular atrophy or spinal muscular atrophy (SMA) type 4 usually begins to appear at 30 years of age and has a relatively benign course [1]. The clinical features of this disease are very similar to SMA type 3, although the adult version is less severe. Life expectancy is normal in such patients [2]. Type 1 and type 2 SMA can occur at any age between birth and 2 years.

Patients classically present with an asymmetric weakness of the proximal muscles of the arms and legs, resulting in hampering of the quality of life [3]. Over time, the muscle wasting spreads to the other limb muscles before involving the central portions of the body. The weakness is associated with pain, in both the normal and affected muscles. Tremors and twitchings are also known to occur [4].

Involvement of the muscles of the thorax may result in respiratory compromise. The affliction of the brainstem may lead to bulbar symptoms such as dysphagia and dysarthria. There are usually no other central nervous system manifestations present. Reports have shown that these patients exhibit a higher degree of intelligence.

The examination may show all the characteristic findings of a lower motor neuron disease, namely absent/decreased reflexes, hypotonia, flaccid paralysis and muscle fasciculations.

Workup

Diagnosis of this disease is dependent on the anamnestic data. Amongst laboratory tests that may be performed, creatine kinase is the most useful, with elevated levels of the enzyme found. In some patients, the enzyme levels may be normal.

Genetic tests may be performed both prenatally and postnatally to check for deletions involving the SMN1 gene [5].

Electrocardiograms (ECGs) are usually normal in these patients [6].

A variety of other neuromuscular diseases may present in a similar manner. Differentiation is done by electrophysiological tests that demonstrate a reduction of transmitted nerve signals [7] [8]. Sensory signals are usually normal in adult spinal muscular atrophy. Tests involving compound motor action potential may also be performed for diagnosis.

Muscle biopsy is another test that may help in differentiating adult spinal muscular atrophy from other similar muscular diseases [9] [10]. These characteristically show atrophy of the muscle fibers with compensatory hypertrophy.

Differential diagnosis usually involves the other spinal muscle atrophies which include the X-linked spinal muscular atrophy, distal spinal muscular atrophy, autosomal dominant spinal muscular atrophy and juvenile asymmetric segmental spinal muscular atrophy. Postpolio syndrome and multifocal motor neuropathy are the other conditions that may present in a similar fashion.

There is a potential for patients with adult spinal muscular atrophy to be misdiagnosed due to the overlapping of clinical features. Over the years, patients labeled earlier as SMA have had their diagnoses revised to more treatable conditions including syringomyelia, amyotrophic lateral sclerosis, myopathy, axonal neuropathies and herniated lumbar discs. It is hence, recommended that patients be followed up for a long duration to establish the correct diagnosis.

Treatment

Prognosis

Etiology

Epidemiology

Sex distribution
Age distribution

Pathophysiology

Prevention

Summary

Patient Information

Self-assessment

References

  1. Wang CH1, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027-1049.
  2. Baioni MT, Ambiel CR. Spinal muscular atrophy: diagnosis, treatment and future prospects. J Pediatr (Rio J). 2010;86(4):261-270.
  3. Prior TW, Russman BS. Spinal Muscular Atrophy. 2000 Feb 24 [Updated 2013 Nov 14]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
  4. Joynt R, Griggs R. Clinical Neurology. Philadelphia: Lippincott; 1997. Vol 4: 11-5.
  5. Arnold WD, Kassar D, Kissel JT. Spinal Muscular Atrophy: Diagnosis and Management in a New Therapeutic Era. Muscle Nerve. 2015;51(2):157-167.
  6. Palladino A, Passamano L, Taglia A, et al. Cardiac involvement in patients with spinal muscular atrophies. Acta Myol. 2011 Dec. 30(3):175-8.
  7. Hausmanowa-Petrusewicz I, Karwanska A. Electromyographic findings in different forms of infantile and juvenile proximal spinal muscular atrophy. Muscle Nerve. 1986 Jan. 9(1):37-46.
  8. Krivickas LS. Electrodiagnosis in neuromuscular disease. Phys Med Rehabil Clin N Am. 1998 Feb. 9(1):83-114, vi.
  9. Buchthal F, Olsen PZ. Electromyography and muscle biopsy in infantile spinal muscular atrophy. Brain. 1970. 93(1):15-30.
  10. Dubowitz V. Muscle disorders in childhood. Major Probl Clin Pediatr. 1978. 16:iii-xiii, 1-282.

  • A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle - TK Rajendra, GB Gonsalvez, MP Walker - The Journal of cell , 2007 - jcb.rupress.org
  • A mouse model of spinal and bulbar muscular atrophy - , PJ Crack, I Kola, SS Cheema, MK Horne - Human molecular , 2002 - Oxford Univ Press
  • Degeneration in Portuguese families of the Azores Islands A new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions - P Coutinho, C Andrade - Neurology, 1978 - AAN Enterprises
  • A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis - AL Nishimura, M Mitne-Neto, HCA Silva - The American Journal of , 2004 - Elsevier
  • A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis - AL Nishimura, M Mitne-Neto, HCA Silva - The American Journal of , 2004 - Elsevier
  • A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure - T Arbizu, J Santamaría, JM Gomez, A Quílez - Journal of the , 1983 - Elsevier
  • A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure - T Arbizu, J Santamaría, JM Gomez, A Quílez - Journal of the , 1983 - Elsevier
  • Vulnerability of motor neurons and dissociation of pre-and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy - LM Murray, LH Comley, D Thomson - Human molecular , 2008 - Oxford Univ Press
  • A controlled trial of riluzole in amyotrophic lateral sclerosis - G Bensimon, L Lacomblez - New England Journal of , 1994 - Mass Medical Soc
  • A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure - T Arbizu, J Santamaría, JM Gomez, A Quílez - Journal of the , 1983 - Elsevier
  • A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure - T Arbizu, J Santamaría, JM Gomez, A Quílez - Journal of the , 1983 - Elsevier
  • Vulnerability of motor neurons and dissociation of pre-and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy - LM Murray, LH Comley, D Thomson - Human molecular , 2008 - Oxford Univ Press
  • Benign spinal muscular atrophy arising in childhood and adolescence - D Gardner-Medwin, P Hudgson, JN Walton - Journal of the neurological , 1967 - Elsevier
  • A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure - T Arbizu, J Santamaría, JM Gomez, A Quílez - Journal of the , 1983 - Elsevier
Self-assessment