SMA (spinal muscular atrophy) is a genetic disease of progressive muscle wasting. Some patients develop symptoms soon after birth, others become ill as adults. SMA - what is this disease? What are the causes of spinal muscular atrophy? What is treatment and rehabilitation? What is the prognosis and what is the patient's life expectancy?

SMA - what is this disease? Characteristics of SMA

SMA- a disease known in Polish asspinal muscular atrophy(EnglishSpinal Muscular Atrophy - SMA ) is a rare genetic disease, the essence of which isweaknessand gradualmuscle wasting . This process is caused by the death of the motor neurons in the front horns of the spinal cord, which are responsible for the work of the muscles. The disease manifests itself, among others :

  • skeletal muscle weakness
  • motor paresis
  • eating disorders
  • respiratory failure

All of them eventually lead to death. In Poland, SMA occurs with the frequency of 1 in 5000-7000 births.

The greatest threats in the course of SMA are weakening of the respiratory muscles, weakening of the muscles of the throat and esophagus, weakening of the trunk muscles and progressive curvature of the spine.

SMA (Spinal Muscular Atrophy): Causes and Inheritance

The reasondying of motor neurons, and further muscle atrophy, isgenetic defect- mutation of the gene responsible for the encoding of SMN, i.e. proteins necessary for the functioning of motor neurons. The information needed for the production of the SMN protein is stored in the SMN1 and SMN2 genes on chromosome 5.

This defect is inherited in an autosomal recessive manner, i.e. in order for a child to become ill, they must receiveone copy of the defective gene from each parent . In a situation where each parent carries one abnormal copy of the gene, the probability of having a child with SMA is 25%. People who only got the mutated gene from one parent are carriers of SMAand usually have no symptoms of the disease.

Katarzyna Pedrycz - mother of Benia (4 years old, SMA I)

We were first visited by a he althy and perky Boguś. Two years later Benedict, known as Beniu, was born. Equally he althy, but a little less lively. He developed properly until 5-6 months. Then he began to lose motor skills. He stopped rising on his forearms, he raised his head less willingly, he did not want to lie on his tummy. -Maybe the lazy hit us ? - my husband and I calmed down each other, trying not to compare Benia to a very efficient brother. However, I confided my dilemmas to a physiotherapist who cared for my spine, which was strained by two pregnancies and childbirths. -Temperament is one thing, but it is worth checking if the little one is developing properly- I heard from her and got contact details for a child rehabilitation therapist. After seeing 7-month-old Benia, she immediately referred us to a neurologist who sent us for a genetic test. They showed that Benio has type I SMA. This means that my husband and I both have one set of genes that are damaged, responsible for the production of proteins. Such "chosen ones" - one in 1600 marriages.

SMA: Spinal Muscle Atrophy Classification

Spinal Muscular Atrophy - SMA is one disease but occurs in 4 main types: SMA I, SMA II, SMA III, and SMA IV. Each of them has different symptoms and the course of the disease.

Typ SMAAge of onsetCommon symptoms
Type 1up to 6 months oldthe sick never sits down
Type IIFrom 6 to 18 months of agea sick person can sit without help, but cannot walk by himself
Type IIIover 12 months of agesteps without support
Type IVover 30walking difficulties arise

SMA: symptoms depend on the type of disease

The symptoms of SMA depend primarily on the form of the disease.

  • Type I (early infant)

Type I, known asformerly known as Werding-Hoffmann disease , is the most severe and common (50% of cases) form of SMA that appears in the first weeks or months of a child's life. The symptoms of the disease are:

  • muscle weakness and laxity
  • difficulty lifting the head - the child is unable to hold it vertically
  • difficulty with body movements - the child is unable to roll over
  • difficulties withbreathing, sucking, swallowing
  • weak cough
  • silent cry

In this type of disease, the greatest risk is the weakening of the respiratory muscles, leading to acute respiratory failure, which is the most common cause of death.

  • Type II (late baby)

Also calledDubowitz disease . In its course, the limb muscles that are closer to the torso are atrophied first, so the thigh muscles are weaker than the calf and foot muscles, and the arm muscles are weaker than the muscles of the forearms and hands.

Symptomsdiseases usually appearbetween 6 and 18 months of age , however it is believed that if the child was unable to (without a backrest) to maintain a sitting position - even if it later lost this ability - this is the second form of SMA. In patients with type II SMA, a significant problem is alsocurvature of the spine(scoliosis).

  • Type III (child and youth)

In type III, formerly known asKugelberg-Welander disease , difficulties with climbing stairs, getting up from the floor or a low armchair appear first. However, before muscle weakness forces the patient to use the wheelchair, he is able to walk or take at least a few steps.

  • Type IV (adult)

Type IV isthe mildest form of SMAthat appears in adulthood, typicallyin the fourth or fifth decade of life . There are only problems with walking. Some specialists do not distinguish the fourth form and classify the mild disease as the late third form.

Katarzyna Pedrycz - mother of Benia (4 years old, SMA I)

We knew absolutely nothing about SMA. After all, the older son, as the tests have discovered, does not even carry the abnormal gene. We found contact with the SMA Foundation, and then with the parents of other children. Our disbelief turned into knowledge and confidence. We learned that our son, not only will he never walk, but also his hand muscles will become weaker and weaker with time. Benio will never sit down and look up by himself. He will slowly lose the ability to eat and breathe independently. And finally SMA will take it away from us … Not as soon as with weak SMA I, i.e. in the second year of life, but not much later.

SMA: diagnostics

The initial diagnosis is made by a neurologist based on symptoms, family history and neurological tests.

If SMA is suspected, the doctor refers the patient to a genetic clinic into perform a genetic test.

Final diagnosis can be madebased on genetic test results .

SMA: rehabilitation

For many years there has been no effective treatment for SMA. In order to ensure the patient's comfort of life and extend it as much as possible, onlysymptomatic treatmentwas implemented, which consisted of multidisciplinary rehabilitation activities.

In 2007, the so-called international standards of care in SMA (Consensus Statement for Standard of Care in Spinal Muscular Atrophy). According to them, treatment should be directed by a neurologist, and the patient should be under the care of many specialists, such as, among others:

  • physiotherapist - the purpose of rehabilitation is to prevent spinal curvatures and contractures, and in the form of SMA3 - it can extend the time of independent walking
  • orthopedist - the goal of treatment is to prevent defects in the spine and limbs
  • dietitian - to maintain the proper functioning of the digestive system, as well as to prevent overweight and obesity, which burden the musculoskeletal system
  • pulmonologist - monitors respiratory functions; his help is needed especially in the 1st and 2nd type of the disease
Katarzyna Pedrycz - mother of Benia (4 years old, SMA I)

We were an ordinary, active Warsaw couple. My son's illness and treatment changed everything … My husband works as much as he can, because only he earns. I quit my job to take care of Ben. Our ideals: to live in the city, to move around by public transport and by bike, collided with the new, hard reality of living with a disabled child. An apartment in a building in the center, on the second floor without an elevator, has become a trap. The apartment itself is not suitable for a wheelchair user. And the stairs prevent Benio from leaving the house alone, and we lose our strength and he alth every day, bringing them up and bearing our son and the equipment thanks to which he moves, which weigh several kilograms. We simply cannot afford an apartment or a house tailored to the needs of Benia with a location in Warsaw. Perhaps we will have to move out to the city. But then commuting to rehabilitation will not be so easy. We are also afraid that in this way we will make it difficult for children to access urban culture and other children. For now, we're trying to live a normal life. Benia's daily exercises - those at home and in rehabilitation clinics - include excursions to cultural events, meetings with family, friends, work and passions, and moments just for us. We only gave up longer plans. Benia's illness taught us this. Do not "assume" that something will happen, but enjoy what is and quicklyreact to the smallest changes.

SMA: treatment for spinal muscular atrophy

After almost 120 years from the time when SMA was first described (1891) and after the unsuccessful search for a cure for this disease, there was hope. Scientists began work on modifying the SMN2gene in such a way that it could encode more SMN proteins. They discovered that such modification can be facilitated by many substances, including: aminoglycosides, tetracycline antibiotics and oligonucleotides. Clinical trials for the first substance containing synthetic nucleotides began in 2013. Soon other molecules were also investigated:

  • branaplam - still under research
  • risdiplam - the manufacturer applied for admission to treatment in the USA

There are also ongoing clinical trials of other molecules: reldesemtiv and SRK-015, which work by strengthening the muscles of a patient with SMA.

Currently, the following substances are available for the treatment of SMA:

  • oligonucleotide- synthetic DNA fragment - a drug that increases the amount of the SMN protein encoded by the SMN2 gene, which restores the functioning of neurons and / or prevents them from dying due to SMA. Due to its size, the drug molecule does not cross the blood-brain barrier, therefore the drug is administered directly to the patient's spinal canal - the so-called intrathecal injection. The drug is administered every 4 months. From 2022, in Poland, treatment with this substance in children and adult patients, regardless of the form of SMA that occurs in them, is reimbursed.
  • gene therapy- consists in "repairing" the damaged SMN1 gene. This is done by "infecting" nerve cells with special viruses that carry the missing piece of the genetic code. Since May 2022, a substance for gene therapy in children with SMA up to the age of 2 has been available in the US. The procedure of approving the drug in the European Union countries is underway.
Katarzyna Pedrycz - mother of Benia (4 years old, SMA I)

We found out that there is a new drug that, together with proper rehabilitation, slows down muscle wasting. The drug replenishes the lack of protein in the spinal cord, but only for about 4 months. Then it is "used up" and another dose has to be given. The drug must therefore be taken throughout life. When the core doesn't get more protein, your muscle wasting starts to worsen.

Thanks to the cooperation with the SMA Foundation, we managed to arrange a trip to France, where Benia was included in the extended charity program and received the first doses of a new SMA drug. This program allowed the most seriously ill patients to benefit from the therapy at the expense of the drug manufacturer until it was reimbursed in a given country. When it happened weFrance, as we were not citizens of that country, we could not continue the treatment there. Fortunately, the attending physician transferred us to a similar program in Belgium. Then we got another gift, and it happened on Christmas 2022. Since then, the drug for Benia has been reimbursed in Poland.

Before treatment, Benio struggled to roll from side to side and only grabbed light objects. Fortunately, we haven't reached the stage of choking on our own breath, saliva and food yet. After 12 doses of the drug and intensive rehabilitation, Benio sits and rides in an active wheelchair, pulls up his legs, raises his arms up, rises on them, eats himself and draws. Until recently, we did not even dream that Benio would change from a pram to a bed. Now we hope that Benio will not only live, but maybe someday, one day, he will live independently …?

If you want to know what Benia's treatment is, read"The story of a hard-working Beni, whose muscles stopped disappearing"

SMA - exoskeleton for children with spinal muscular atrophy

In June 2016, the Spanish Research Committee (Consejo Superior de Investigaciones Científicas, CSIC) unveiled the world's first exoskeleton for children aged 3-14 years with spinal muscular atrophy. It consists of adjustable orthoses that adjust to the length of the child's legs and torso. Instead of joints, there are motors that mimic human muscles. The exoskeleton is intended to help patients walk and prevent, among other things, lateral curvature of the spine.

Video source: youtube.com/CSIC Comunicación

SMA: prognosis

It is difficult to clearly definelife expectancyas it varies greatly depending on the quality of care and individual differences between patients. However, it is known that most children with Type II disease enter adulthood safely. On the other hand, the life expectancy of people with mild SMA (type III) does not differ from the average. Such people often start families and have great academic and professional achievements.

The introduction of new drugs for SMA into therapy gives hope not only to significantly improve the quality, but also to extend the life of people with SMA. It is already known that the sooner a child is given the currently available SMA drug, the better it develops. In many cases, the symptoms of SMA are completely invisible. Even in children with the most severe type of SMA I.

Where to go for help

SMA Foundation

People with spinal muscular atrophy and their relatives can seek help from the SMA Foundation. Its goal is, inter alia, conducting comprehensive activities for the benefit of people suffering from spinal atrophymuscles and their relatives, including those aimed at preventing exclusion, increasing independence and improving the broadly understood quality of life, increasing the availability of diagnostic, therapeutic and rehabilitation methods and techniques, as well as products and technological solutions for people suffering from spinal muscular atrophy, as well as supporting systemic solutions , in particular in the field of he alth care and social security, taking into account the needs of people with spinal muscular atrophy and their relatives.

More information can be found on the foundation's website: www.fsma.pl.

Category:

Genetic diseases