Spinal Muscular Atrophy Type 3

Spinal Muscular Atrophy Type 3

Spinal Muscular Atrophy (SMA) type 3, formerly known as Kugelberg Welander disease, is the rarest of the childhood onset types of SMA, accounting for less than 20% of cases diagnosed before adulthood.1 Patients with this form of SMA will appear healthy in early life with a more insidious onset of weakness than is seen in types 0-2. Symptomatic proximal weakness appears on average after the age of 9 years old, but initial weakness can occur as early as 18 months.1,2

The hallmark weakness and loss of tone associated with type 3 SMA will usually manifest as clumsy walking, new onset falling, and in some cases, a rapid loss of lower extremity function. The natural history of type 3 SMA is variable with periods of progression followed by plateaus of function in late childhood, puberty, and adolescence.3 A steady, progressive decline in muscle strength and endurance invariably begins in the second decade of life.3 Patients with type 3 SMA can be divided into ambulatory and non-ambulatory subgroups, with the non-ambulatory  patients obviously being the more severely affected as the disease can progress to involve upper extremities and neck musculature.3 Scoliosis is a common complication in adolescence and adulthood resulting from differential involvement between opposing tonic muscle groups.2,4

Physical examination will reveal proximal weakness especially in the legs and gait derangement.2,5 Electromyography in patients with type 3 disease can show reduced spontaneous activity but unlike SMA types 0, 1, and 2 in which the compound muscle action potential amplitude (CMAP) is always reduced, the CMAP amplitude may be normal in 25% of type 3 cases.6

As in other forms of SMA, there is no expectation of encephalopathy, and sensory function is preserved.2 A majority of patients with type 3 SMA reported functional independence in a large clinical database.1

Mortality before adulthood due to the sequelae of type 3 SMA is rare, occurring in fewer than 1% of type 3 SMA patients.1 A lifespan comparable to healthy individuals is achievable in most type 3 SMA patients if complications such as scoliosis are addressed and ambulation issues are mitigated with assistive devices such as walkers or wheelchairs.1-3

References

1. Belter L, Cook SF, Crawford TO, et al. An overview of the Cure SMA membership database: Highlights of key demographic and clinical characteristics of SMA members. J Neuromuscul Dis. 2018;5(2):167-176.

2. Chabanon A, Seferian AM, Daron A, et al. Prospective and longitudinal natural history study of patients with Type 2 and 3 spinal muscular atrophy: Baseline data NatHis-SMA study. PLoS One. 2018;13(7):e0201004.

3. Montes J, McDermott MP, Mirek E, et al. Ambulatory function in spinal muscular atrophy: Age-related patterns of progression. PLoS One. 2018;13(6):e0199657.

4. Durmus H, Yilmaz R, Gulsen-Parman Y, et al. Muscle magnetic resonance imaging in spinal muscular atrophy type 3: Selective and progressive involvement. Muscle Nerve. 2017;55(5):651-656.

5. Montes J, Dunaway S, Garber CE, Chiriboga CA, De Vivo DC, Rao AK. Leg muscle function and fatigue during walking in spinal muscular atrophy type 3. Muscle Nerve. 2014;50(1):34-39.

6. Yuan P, Jiang L. Clinical characteristics of three subtypes of spinal muscular atrophy in children. Brain Dev. 2015;37(5):537-541.