A natural history study of late onset spinal muscular atrophy types 3b and 4
- First Online:
- 225 Downloads
Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron (SMN)1 gene. The nearly identical SMN2 gene plays a disease modifying role. SMA is classified into four different subtypes based on age of onset and clinical course (SMA types 1–4). The natural history of early onset SMA types 1–3a has been studied extensively. Late onset SMA is rare and disease course has not been studied in detail.
To perform a prospective study on the clinical course and the correlation with SMN2 copy numbers of late onset SMA.
Patients fulfilling the diagnostic criteria for late onset SMA (types 3b and 4) were included in the study. At inclusion and follow-up, muscle strength, respiratory function, functional status and quality of life were assessed. SMN2 copy number was determined in all patients.
Twelve patients were identified and included. Six patients were siblings from one family, two patients were brothers from a second family and four patients were sporadic cases. All patients carried four copies of the SMN2 gene. Median age of disease onset was 22.2 years (10–37). Age of disease onset in patients from family one was lower as compared to the other patients. None of the outcome measures changed after a follow-up of 2.5 years. Five patients reported an increase in fatigue and muscle weakness. None of the patients showed symptoms of respiratory insufficiency.
This study indicates that late onset SMA is not characterized by disease progression and that alternative or surrogate disease markers are required for the design of future trials. This study confirms the finding that SMN2 copy number is a SMA disease course modifier.
Key wordsspinal muscular atrophy natural history survival motor neuron
Unable to display preview. Download preview PDF.
- 1.The Amyotrophic Lateral Sclerosis Functional Rating Scale. Assessment of activities of daily living in patients with amyotrophic lateral sclerosis. The ALS CNTF treatment study (ACTS) phase I–II Study Group. Arch Neurol 53:141–147Google Scholar
- 8.Escolar DM, Buyse G, Henricson E, Leshner R, Florence J, Mayhew J, Tesi- Rocha C, Gorni K, Pasquali L, Patel KM, McCarter R, Huang J, Mayhew T, Bertorini T, Carlo J, Connolly AM, Clemens PR, Goemans N, Iannaccone ST, Igarashi M, Nevo Y, Pestronk A, Subramony SH, Vedanarayanan VV, Wessel H (2005) CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy Ann Neurol 58:151–155PubMedCrossRefGoogle Scholar
- 11.Great Lake ALS Study Group (2003) A comparison of muscle strength testing techniques in amyotrophic lateral sclerosis Neurology 61:1503–1507Google Scholar
- 17.O’hagen JM, Glanzman AM, McDermott MP, Ryan PA, Flickinger J, Quigley J, Riley S, Sanborn E, Irvine C, Martens WB, Annis C, Tawil R, Oskoui M, Darras BT, Finkel RS, De V (2007) An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients. Neuromuscul Disord 17:693–697PubMedCrossRefGoogle Scholar
- 24.Tomaszewicz K, Kang P, Wu BL (2005) Detection of homozygous and heterozygous SMN deletions of spinal muscular atrophy in a single assay with multiplex ligation-dependent probe amplification Beijing Da Xue Xue Bao 37:55–57Google Scholar