Spinal Muscular Atrophy (SMA) in Children

00:02 When children are weak, sometimes the problem is in the motor nerve.

00:06 In this lecture, we'll talk about specific motor nerve disorders that could occur in pediatrics.

00:13 Let's start with Spinal Muscular Atrophy or SMA.

00:18 SMA is often a very debilitating condition.

00:22 it's autosomal recessive in that it may travel in families.

00:26 and have unaffective carriers.

00:29 The defect is on the survival motor neuron gene or the SMN gene It results in a degeneration of the anterior horn cells of the spinal cord.

00:40 resulting in weakness.

00:43 There are three main types of SMA.

00:46 I, II and III.

00:47 SMA I is very severe.

00:50 It usually affects infants and is often life threatening.

00:54 SMA II is more moderate and SMA III is quite mild.

01:01 All of the SMAs, the problem is that small muscles are not innervated.

01:06 The larger ones still have innervations.

01:09 So, in muscle biopsy it will show a patchy appearance.

01:13 Much like this.

01:14 Patients will present with a progressive symmetrical proximal weakness.

01:20 Remember this is a lower motor neuron disease.

01:23 So, they will be floppy and may have absent deep tendon reflexes.

01:29 You may see muscle fasciculation as well.

01:31 And it is often seen easily in the tongue.

01:35 But remember, it is just the motor neurons.

01:37 These patients will have normal cognition.

01:41 Let's review the natural progression of disease without any effective therapy, which has only recently been discovered and instituted in the last 15 years.

01:49 Type one results in severe hypotonia in children.

01:53 Death before the age of 2 is common without therapy.

01:55 These patients will die of respiratory complications if untreated.

01:59 In Type II disease, they may have the ability to sit but often will not have the ability not walk.

02:06 This typically presents a little later around 6-18 months of age.

02:10 And it requires nutrition and respiratory support.

02:15 In Type III disease, patients may lose the ability to ambulate around 10 years of age.

02:22 It often presents after a year an a half of age and typically we will involve Physical therapy and orthopedics for braces or things like that so to they can function as long and as well as possible.

02:36 So, the diagnosis of SMA is made by a genetic test of the SMA I gene.

02:43 We'll send it for sequencing and look for deletions.

02:48 New treatments have come out for SMA including two new treatment options — a gene replacement therapy called Zolgensma and a drug called nusinersen.

02:59 SMA gene therapy is a one-time infusion that replaces the defective or missing SMN1 gene with a working copy.

03:07 This new gene increases survival motor neuron (SMN) protein levels, which improves motor neuron function and increases the likelihood of survival.

03:15 Recently, the FDA approved this treatment for children less than 2 years of age with SMA.

03:21 A child must have the SMN1 mutation that causes this disease to receive this therapy.

03:26 The FDA approved the use of this drug for all types of SMA with an SMN1 mutation, from infant-onset SMA type 1 to adult-onset SMA type 4.

03:37 Nusinersen uses synthetic (man-made) genetic material called antisense oliigonucliotide to improve the splicing of the SMN2 gene.

03:47 This helps children to make more SMN protein needed for healthy motor neurons.