This book describes Spinal muscular atrophy, Diagnosis and Treatment and Related Diseases

Recently a 5 month old Singapore boy diagnosed with Spinal muscular atrophy Type 1 will be able to obtain the $3 million Zolgensma single dose medicine treatment. This medicine is the most expensive medicine in the world. This is to be followed by a regime of Risdiplam costing $15,000 for 64 days and possible steroids to prevent liver damage.

Spinal muscular atrophy is a genetic disorder featured by weakness and wasting (atrophy) in muscles utilized for movement (skeletal muscles).

It is produced by a loss of specialized nerve cells termed motor neurons that regulate muscle movement.

The weakness is likely to be more severe in the muscles close to the center of the body (proximal) compared to muscles away from the body's center (distal).

The muscle weakness normally becomes worse with age.

There are many types of spinal muscular atrophy produced by alterations in the same genes.

The types differ in age of start and severity of muscle weakness with overlap between the types.

SMA type 0 (Congenital disease) - evident before birth and is the rarest of the SMA

SMA type I (Werdnig-Hoffmann disease) - affects babies less than six months old.

SMA type II (Dubowitz disease) - develops in babies between 7 and 18 months old.

SMA type III (Kugelberg-Welander disease) - appears after 18 months of age.

SMA type IV (Adult disease) - this type of SMA patients is diagnosed in adulthood.

Other types of SMA and linked motor neuron diseases are caused by mutations in other genes such as:

Spinal muscular atrophy that has progressive myoclonic epilepsy,

Spinal muscular atrophy that has lower extremity predominance,

X-linked infantile spinal muscular atrophy, and

Spinal muscular atrophy that has respiratory distress type 1.

Congenital spinal muscular atrophy with arthrogryposis (persistent contracture of joints with fixed abnormal posture of the limb)

Kennedy’s disease, termed progressive spinobulbar muscular atrophy, may first be identified between 15 and 60 years of age.

Distal spinal muscular atrophy (DSMA) a type of spinal muscular atrophy that mostly involves the hands, feet, lower arms, and lower legs.

The symptoms of spinal muscular atrophy happen depending on the type of SMA present in the affected person, and the age the person acquires the genetic disorder:

Weakness in muscles with sudden jolting movements

Difficulty in breathing and swallowing of food

Irregular shape of limbs, chest, spine due to a decrease in muscle strength

Problems with sitting, standing and walking normally

Higher risk of acquiring respiratory disorders and infections

Diagnoses could be made by prenatal screening or by gene panel investigation and muscle biopsy.

Polymerase chain reaction (PCR) or multiplex ligation probe amplification (MLPA) can help to determine the homozygous exon 7 deletion in the SMN1 gene.

The treatment has mainly been supportive in the past

Physiotherapy-non-invasive ventilation, Airway clearance

Gene Therapy

Stem Cell Therapy

New treatments have been produced that are combating the very poor morbidity and mortality linked with SMA I and II.

Zolgensma is a single dose intravenous injection gene therapy that allow the body to produce functioning SMN protein.

All patients were alive at 20 months compared to expected 8% in other therapies

Risdiplam is an oral medicine that acts via modifying SMN2 splicing.

Nusinersen is an intra-thecally delivered antisense oligonucleotide (ASO) that provides functional SMN2 formation

TABLE OF CONTENT

Introduction

Chapter 1 Spinal muscular atrophy

Chapter 2 Causes

Chapter 3 Symptoms

Chapter 4 Diagnosis

Chapter 5 Treatment

Chapter 6 Prognosis

Chapter 7 Muscle Atrophy

Chapter 8 Floppy Baby

Epilogue