Finkel type SMA
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Finkel type spinal muscular atrophy (FSMA) is a form of adult-onset spinal muscular atrophy (SMA), a disease that affects motor neurons, the nerve cells that control muscle movement. FSMA is caused by mutations in the VAPB gene.
FSMA was first described by Brazilian neurologist Nunjo Finkel, MD, in 1962, who noted four cases of patients in the same family with what he described as a “late pseudomyopathic form of heredo-familial progressive muscle atrophy.” Researchers have gone on to describe the condition as prevalent in people of Portuguese Brazilian descent. Additional reports indicated that the condition also is present among people in northern Germany.
People with FSMA generally have a normal lifespan, although they may need support or assistance with such daily activities as walking as they age and certain muscles weaken.
Other forms of SMA, which are caused by mutations in the SMN1 gene, are divided into five main types — 0, 1, 2, 3, and 4. FSMA is one of the rare SMA types, characterized by its slow progression. Other rare types include lower extremity dominant (SMA-LED), SMARD1, Kennedy’s disease, and X-linked infantile SMA.
What causes FSMA?
FSMA is a disease inherited in an autosomal dominant manner, meaning that a single copy of the mutated vesicle-associated membrane protein-associated protein B (VAPB) gene is sufficient to cause the disease.
Parents with FSMA have a 1 in 2, or 50%, risk of passing the mutated gene to their children. If both parents have a gene copy of the disease-causing mutation, their children would have a 3 in 4, or 75%, risk of inheriting the disease-causing gene and developing the disease.
The VAPB gene contains the instructions for the production of a protein that exists in cells throughout the body, but whose function is not fully understood. The protein is located in the membrane that surrounds a cellular structure called the endoplasmic reticulum.
Among its various duties, the endoplasmic reticulum folds new proteins and prepares them for transport within a cell or to the cell surface.
To do its work correctly, the endoplasmic reticulum relies on a system that detects the buildup of unfolded or misfolded proteins called the unfolded protein response (UPR). This aberrant buildup of misfolded proteins causes biological stress that is thought to be a key factor behind certain neurodegenerative diseases.
Scientists believe the protein encoded by the VAPB gene plays a role in UPR. A mutated or abnormal VAPB contributes to a defective unfolded protein response and, as a result, abnormal proteins accumulate in cells, resulting in cell death.
Nerve cells that control muscle movement appear to be particularly vulnerable to these protein aggregates. The progressive loss of these nerve cells leads to FSMA and disease symptoms.
A specific mutation of the VAPB gene is also responsible for one type of inherited amyotrophic lateral sclerosis (ALS).
Due to its pattern of inheritance, FSMA also is known as autosomal dominant adult-onset SMA and autosomal dominant adult-onset proximal SMA, Finkel late-adult type SMA, and Finkel disease.
What are the symptoms of FSMA?
Two signs of FSMA are severe weakness of the abdominal muscles, which result in a prominent abdomen, and low back lordosis, also known as swayback.
The condition is slowly progressive, and symptoms first appear in the lower limbs, and then spread to the upper limbs. Like the other adult-onset form — SMA type 4 — FSMA generally has mild symptoms compared to those occurring in types 0 to 3, which develop in infants and children.
FSMA symptoms will slowly progress over time, from muscle weakness to atrophy.
FSMA mostly affects the proximal muscles, or those closest to the body’s middle, and is characterized by:
- muscle cramping of the limbs and abdomen
- weakness in the leg muscles, causing a waddling gait
- involuntary muscle contractions
- fasciculation (a brief spontaneous contraction affecting a small number of muscle fibers, often causing a flicker of movement under the skin)
- reduced or absent reflexes
- spontaneous fits of suffocation
- symptomatic myotonia (inability to relax your muscle quickly after it contracts)
- chronic intestinal constipation
- sexual dysfunction.
In more severe cases, a person with FSMA may experience difficulty walking and breathing.
FSMA is different from other types of SMA in that it is developed in adulthood, the specific gene mutation of VAPB and inheritance pattern, and its slow progression.
How is FSMA diagnosed?
Diagnosis of FSMA involves taking a physical exam, reviewing the health history in the family, and undergoing genetic testing.
The physical exam looks at the muscles affected and tests for reflexes. The family medical history is used to identify anyone who had spinal muscular atrophy or another inherited muscular dystrophy.
Genetic testing involves getting a blood sample, which is sent to a lab specializing in rare diseases. If the test is inconclusive, an electromyogram and muscle biopsy may be requested. Electromyography is a test that assesses the health of muscles and motor neurons — the nerve cells that control voluntary muscle movement, which die off in SMA.
What treatment options are available for FSMA?
FSMA treatments involve managing disease symptoms and focusing on improving quality of life. Physical therapy is used to preserve range of motion, increase muscle strength, and prevent joint contractures (shortened muscles and tendons at joints).
People with FMSA may benefit from using specialized equipment, such as walkers and wheelchairs for mobility and other adaptive aids for living with spinal muscular atrophy.
At this point, there is no gene therapy available for FSMA.
What is the life expectancy for people with FSMA?
People with FSMA generally have a normal life expectancy, although they may need support or assistance with daily activities as certain muscles weaken and their mobility worsens with age.
SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Finkel type SMA
Finkel type spinal muscular atrophy (FSMA) is a form of adult-onset spinal muscular atrophy that is caused by mutations in the VAPB gene. It has a slow progression, and is marked by weakness in the lower limbs that gradually spreads to upper limbs.
Yes, only adults are known to have Finkel type spinal muscular atrophy (FSMA).
Yes, due to the slow progression of Finkel type SMA (FSMA), the majority of people are able to walk. Later in life, adaptive equipment such as walkers or wheelchairs may be needed.
No, there is no cure for Finkel type SMA (FSMA) or spinal muscular atrophy in general. Treatment for FSMA is usually focused on the management of disease symptoms and on improving quality of life. The use of specialized equipment and physical therapy can be of benefit to this patient population.
At this point, there is no gene therapy suitable for Finkel type spinal muscular atrophy (FSMA). Children up to age 2 with one of the main types of SMA, however, can be eligible to receive treatment with Zolgensma — the only gene therapy approved for SMA.
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