Introduction:
Intermediate spinal muscular atrophy (SMA) type 2 is called Dubowitz disease. The disease is inherited in an autosomal recessive pattern. The condition develops in a child of six months to 18 months old. The disease occurs frequently in the lower limb. The affected children can sit up but are unable to walk. Most children survive to adulthood.
What Is Intermediate SMA Type 2?
Intermediate SMA type 2 is a rare genetic disorder with progressive loss of lower motor neurons (nerves cell controlling voluntary movement) resulting in muscle weakness and wasting.
The disease develops during infancy. Mutations in both copies of the SMN1 (survival motor neuron) gene, which are responsible for forming proteins essential for motor neuron and muscle health. The disease is further classified into Type II A and II B. Type II A patients lose the ability to sit independently but Type II B patients retain the ability to sit.
What Are the Symptoms of Intermediate SMA Type 2?
The distinctive feature of the disease is progressive muscle weakness that is more pronounced in the legs than in the arms. The muscles of the chest, throat, and mouth can also be affected by this disease.
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Low muscle tone causes the limbs to become flabby (lose muscle). The loss of muscle tone is more prominent among muscles closest to the trunk such as shoulders, hip, and back. Facial and eye muscles are unaffected.
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The patient experiences absence of deep tendon reflexes. For example, the lack of knee reflex when tapped. Some children during the early course of the disease have distal reflexes (Achilles tendon, muscle connecting calf to heel).
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Contractures of muscle and connective tissue around the joint cause it to become short and hardened.
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Most patients experience a postural tremor in their hands known as polyminimyoclonus.
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Affected individuals show delayed milestone attainment and motor development. When the disease is left untreated the child faces difficulties to stand or walk without help but they may sit up on their own. The patients may lose the ability to sit gradually.
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Weakness of muscle in the mouth causes difficulties in eating, chewing, and swallowing. Few patients have tongue fasciculations (twitching).
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Chest muscle or intercoastal weakness results in breathing and coughing difficulties. The patients may develop lung infections or restrictive lung disease (reduction in lung volume capacity for air). It can be overcome with airway clearance or noninvasive lung support.
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Weakness of the back muscle leads to scoliosis (sideway curvature of the spine). Hip dislocations are also common.
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Patients with movement disabilities have a high-fat index and are at risk of being overweight.
How Are Intermediate SMA Type 2 Diagnosed?
Patients with clinical features and family history are suspected of the disease. In individuals with a family history of the disease, prenatal screening of fetuses or newborns are necessary. Genetic testing of suspected patients can detect disease-causing mutations in the SMN1 gene.
The SMN2 gene is known to influence disease severity. The DNA (deoxyribonucleic acid) testing of blood can measure copies of the SMN2 gene. The disease severity is low in patients with a high number of SMN2 gene copies. In patients with intermediate SMA type 2, three copies of SMN 2 are frequently found. Since the disease is an inherited condition genetic testing helps identify carriers.
If there is confusion about the evaluation of genetic studies. The individuals undergo a further examination with an electromyogram or muscle biopsy. This is not a confirmatory test for the disease.
Electromyograms examine the status of muscles and neurons that supply them. This method can also record muscle response to electrical stimulations by neurons. Whereas, the muscle biopsy requires a small portion of muscle tissue from the upper thigh or other regions to look for disease characteristics.
What Are the Treatment Options for Intermediate SMA Type 2?
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Disease-Modifying Therapy:
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There are three drugs approved for the treatment. The drugs are Spinraza, Evrysdi, and Zolgensma and are non-specific therapy for intermediate SMA type 2.
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Spinraza (nusinersen) is administered to the spine by injection. The drug acts by masking signals from the SMN2 gene which causes the protein to be shorter than usual. Treatment starts with four loading doses followed by a maintenance dose administered every four months. The medication is approved for all age groups, patients and forms of the disease.
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Evrysdi (risdiplam) is administered daily. The drug increases SMN protein production from the SMN2 gene. The medication can be taken orally or through a feeding tube. The medications are approved for all major forms of SMA in patients above 2 months of age.
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Zolgensma (onasemnogene abeparvovecxioi) is a gene therapy. A healthy copy of the SMN1 gene is delivered by adeno-associated virus 9 (AAV9, modified virus) to increase SMN protein production. The medication is administered once. The drug is approved for use in all main types of SMA in infants and toddlers till two years of life.
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The approved medication can slow the disease progression but cannot reverse the damage in the body. Early initiation of therapy can provide better outcomes. However, patients with moderate to advanced stages of the disease require supportive care.
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Supportive Therapy:
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Motor function and support posture are enhanced with physical therapy and exercises.
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Occupational therapy helps patients with their day-to-day activities.
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Speech and language therapy can help the patient with chewing and swallowing.
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The patient’s breathing ability is enhanced with respiratory therapy.
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Strollers and wheelchairs can help patients with severe diseases with mobility.
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Specialized seats or chairs help with feeding and bathing.
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Using braces or standards provide structural support.
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Lung functions are supported with ventilators or cough assistance devices.
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Patients facing difficulties eating are assisted with gastrostomy tubes.
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Diet counseling is necessary to maintain good nutrition and digestion.
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Palliative care improves the quality of life in patients suffering from the disease for a long duration.
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What Is the Prognosis for Intermediate SMA Type 2?
The prognosis differs based on disease severity. Most patients survive to early adulthood without adequate treatment. There is no available cure for the disease but the currently approved medication slows the disease progression. When these treatments are provided during the early stage of the disease the patient can attain developmental milestones without many difficulties.
Conclusion:
The patients suffering from intermediate SMA type 2 are normal at birth. The disease develops between six to eighteen months and varies in severity. The defining feature of the disease is the inability to stand or walk on their own. However, the patient can sit without any external help which is lost as the disease progresses. Most patients leave up to early adulthood or longer.
