Finkel type SMA (SMAFK) is a rare type of adult-onset (or late-onset) spinal muscular atrophy (SMA). SMA is a group of neuromuscular disorders that cause loss of motor neurons (nerve cells that control muscles) in the spinal cord, resulting in weakness, muscle atrophy, and loss of motor function. SMAFK, also called autosomal dominant adult-onset proximal SMA, develops in adults and is a much less severe form of SMA than the type that occurs in infants and young children.
Unlike the most common types of SMA, SMAFK is caused by a specific genetic mutation in a gene called VAPB. This same genetic mutation is also seen in a rare form of inherited amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), another neuromuscular disease. SMAFK is a very rare disease. The incidence and prevalence of the disease are not known, but it is more prevalent in people of Portuguese Brazilian descent. People with SMAFK can have a normal life expectancy.
Like other types of SMA, the principal symptom of SMAFK is progressive muscle weakness and atrophy due to the loss of spinal motor neurons. SMAFK is a proximal spinal muscular atrophy, meaning that it primarily affects parts of the body closer to the center, such as the torso, upper legs, and upper arms. SMAFK is slowly progressive, with symptoms including weakness, tremors, and muscle twitching (fasciculations) developing very slowly over time. Symptoms often first appear in the lower limbs and then spread to the upper limbs.
SMAFK symptoms do not develop until adulthood, usually after age 30. Symptoms of SMAFK and other forms of adult-onset SMA (like SMA type 4) are generally very mild compared to symptoms seen in SMA that develop during infancy and childhood. However, severity can vary, even between members of the same family who have the disease.
Typical symptoms include:
Diagnosis of SMAFK involves a family medical history, physical exam, and genetic testing. A family medical history can identify if any family members have been diagnosed with SMAFK, ALS, or other inherited muscular dystrophies. A thorough physical exam is needed to identify which specific muscle groups are affected and test for abnormal reflexes and sensory deficits.
Genetic testing, using a blood sample, is the primary way to diagnose SMAFK, as well as other types of SMA and inherited muscular dystrophies. Before genetic testing was available, a muscle biopsy (taking a sample of muscle tissue) and an electromyogram (EMG) were used for diagnosis. Muscle biopsy and EMG may be used if genetic testing is inconclusive (does not lead to a definite diagnosis).
There is currently no treatment for SMAFK (gene therapy is the primary treatment for most cases of SMA), but symptoms can be managed to preserve mobility and quality of life. Physical therapy to strengthen muscles and maintain range of motion is perhaps the most important way to preserve mobility and prevent debilitating joint contractures (shortening of the muscles and tendons at joints).
SMAFK is distinct from other types of SMA because of its age of onset, slow progression, specific genetic mutations, and pattern of inheritance.
SMAFK is one of the few types of SMA that does not develop until adulthood. Most types of SMA affect infants and young children, but a few affect older children (SMA3) and adults (SMA4 and some cases of SMA-LED). Symptoms typically begin after 30 years of age and may not appear until much later in life. When symptoms do appear, they progress very slowly and may not lead to significant loss of function.
Most cases of SMA are caused by a mutation in the SMN1 gene that instructs the body to create, or encode, the survival motor neuron (SMN) protein. SMAFK is caused by one specific mutation in the VAPB gene, which is found on chromosome 20. The VAPB gene encodes a protein called vesicle-associated membrane protein-associated protein B. This protein plays a role in intracellular transport, the movement of proteins, and other material inside a cell.
One specific mutation, called P56S-VAPB, causes SMAFK and one type of inherited ALS. This mutation produces a malfunctioning VAPB protein that can cause cell death due to stress from a process called the unfolded protein response. Unfolded protein response leads to the accumulation of unfolded, or incompletely constructed, proteins in the cell. People who have this mutation have it in all cells in their body, and it is not known why degeneration is seen more in motor neurons than in other cells.
The most common types of SMA are due to the autosomal recessive inheritance of a gene mutation, meaning that the mutated gene that causes the disease must be inherited from both parents. SMAFK is autosomal dominant, meaning that a gene mutation only needs to be inherited from one parent to cause disease. Autosomal dominant diseases such as SMAFK have a 50 percent chance of being inherited by children and tend to appear in clusters where multiple family members across several generations have the disease.
On mySMAteam, the social network for people with SMA, members come together to ask questions, give advice, and share their stories with others who understand life with spinal muscular atrophy.
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