SMA is an autosomal recessive genetic disorder which means the affected child acquires 2 copies of the mutated carrier gene (1 each from both parents). The parent is a carrier and not affected by the disease. If both parents are carriers, there is 25% chance of having a child affected with SMA.

There are X-linked SMAs linked to the maternal chromosome. X-linked spinal muscular atrophy type 2 (SMAX2 and XLSMA) is also known as arthrogryposis multiplex congenita X-linked type 1 (AMCX1). This type is caused by a mutation in UBA1 gene and passes on from carrier mothers to affected sons.

The most common type of SMA is linked to chromosome 5. Type 1 to 4 are caused by a deficiency in the SMN protein when the mutation is present in both copies of the SMN1 gene on both the maternal and paternal chromosome 5. The deficiency in the SMN1 gene can be partially made up the neighboring SMN2 genes which also produces some functional protein. The number of SMN2 genes varies with each individual and determines the severity of the chromosome 5-related SMA. The greater the number of SMN2 genes, the later the onset and lesser the severity of the disease.

In Type 1 SMA (infantile-onset or Werdnig-Hoffmann disease), the condition is present at birth and babies usually have certain symptoms like weak cry, respiratory trouble and muscle weakness. In many cases, babies are unable to suck normally and rare reach development milestones like turning over or sitting up without assistance. Type 1 babies usually have just 2 copies of the SMN2 genes.

Type 2 or intermediate SMA usually manifests between the ages 8-18 months. The child is generally able to stand and walk on his/her own but presents with muscle weakness and wasting. Type 2 SMA usually has at least 3 SMN2 genes.

Late-onset SMA (Type 3 and 4, mild SMA, adult SMA and Kugelberg-Welander disease) present with different levels of muscle weakness. Type 3 usually presents after the child is around 1.5 years of age and most children are able to stand and walk with the support of aids. Type 4 or adult-onset SMA occurs in adulthood and most adults are mobile and able to walk independently. People with Type 3 and 4 SMA have anywhere between 4 – 8 SMN2 genes which are able to produce a fairly good quantity of the protein.

Some of the types of SMA not related to chromosome 5 include:

• Spinal Muscular Atrophy with Respiratory Distress (SMARD) – a rare form of SMA caused by defects in the IGHMBP2 gene.
• Distal SMA – which mostly affects the hand and feet muscles. This type of SMA can either be autosomal recessive from both parents or autosomal dominant inherited from one parent. X-linked distal SMA is inherited from the mother and only presents in males. Some of the genes associated with various forms of distal SMA include UBA1, DYNC1H1, TRPV4, PLEKHG5, GARS and FBXO38
• Mutations in the cytoplasmic dynein 1 heavy chain 1 (DYNC1H1) gene on chromosome 14 leads to another rare form of SMA known SMA-LED. This mainly affects the leg muscles

• Type 0 SMA is the most severe form with swallowing difficulties, breathing trouble and joint issues
• Type 1 is the most common and severe form. Infants usually present with symptoms before 6 months. They cannot turn over, sit independently and have poor motor coordination and muscle development. Babies may also present with issues in sucking and swallowing. Many babies with severe respiratory distress usually die before the age of 2
• Type 2 affected individuals usually present with signs and symptoms between 6 and 12 months of age. They may be able to sit independently but may not be mobile
• Type 3 affected individuals may be able to walk with difficulties but usually have trouble with stairs. In Type 3 individuals, the legs are severely affected
• Type 4 affected individuals, muscle weakness starts after the age of 10 and such individuals are usually mobile though with muscle weakness

If the pediatrician suspects one of the SMA types, he/she will usually take a family history and history of the child’s symptoms along with a detailed clinical examination. Some of the tests that are used to diagnose SMAs include:

• blood test for an enzyme called creatine kinase (CK) which is usually elevated when muscles are deteriorating
• physical examination to check for muscle wasting and weakness
• genetic testing – to check for various genotypes of SMAs

Currently, no specific treatment or cure is available for the SMAs. Treatment is aimed at preventing complications and enabling independent living. An interdisciplinary team of doctors including pediatricians, neurologists, orthopedicians, pulmonologists and physiotherapists will be required to take care of the clinical needs of the child/adult. In the early stages when just diagnosed, it is important to immediately start physiotherapy and rehab to prevent further deterioration and maintain a certain level of mobility.

Physiotherapy is highly recommended to preserve muscle strength. Wheelchairs may be required in some cases. Adaptive devices are also useful to perform daily tasks.

Children with SMA presenting with breathing problems may require ventilation either non-invasive (through external oxygen) or tracheostomy. Prolonged respiratory care may be required with cleaning of respiratory secretions with mechanical devices to prevent infections. It is important to prevent bronchial infections especially pneumonia. All children and adults with SMA must be vaccinated with flu shots and pneumococcal vaccination.

Babies with feeding difficulty may be required to be fed via alternative methods like a gastrostomy tube.

Children who develop scoliosis may require back braces or surgery for straightening the spine.

Currently the only FDA-approved drug for SMA is Nusinersen marketed as Spinraza by the pharma cos Biogen. Spinraza has proved to be beneficial not only for children but also adults. It can improve muscle quality, mobility and prevent further deterioration of muscles. Spinraza is an injection (12mg/5mL). Spinraza is not yet available in India and patients have been engaged in advocacy to get the Indian government and health authorities to get the drug.

If there is a known case of SMA in the family, it is absolutely essential for closest female relatives like siblings, uncles, aunts and cousins to test for carrier status.

If a woman with a carrier status is pregnant, prenatal test is essential to determine if the fetus has the disease mutation.