The hereditary, degenerating brain disease ADCA-SCA

The brain consists of three parts: the big brain, the small brain and the brainstem. In the small brain, the many nerve cells serve, among other things, for moving and speaking. ADCA (Autosomal Dominant Cerebellar Ataxia) is a rare hereditary neural tissue disease. The nerves shrivel and cannot properly transmit their signals to the muscles. Someone who is affected then walks as if he or she is drunk. When it is clear which piece of DNA is causing this disease, the ADCA is named SpinoCerebellar Ataxia (SCA), followed by a number.

Small brain (cerebellum)

The small brain is located at the back of the head. Together with the big brain and the brainstem, they form the brain. The small brain is the center where by far the most nerve cells are located. Nerve cells that coordinate a large number of body functions. Functions such as:
  • the movement of a body (but not necessarily for muscle contraction);
  • the balance of a body;
  • automatic operations;
  • eye motor skills;
  • language;
  • emotional processes;
  • the working memory (including the short-term memory).

The small brain consists of two halves and lie under the large brain in mind. The outer surface (bark) of the small brain is strongly folded, so that many cells have a place.

Ataxia and causes

Ataxia is a damage in the small brain. The damage causes the movement to go uncoordinated and looks like a 'drunken run' so that the overall impression is a clumsy or drunk person. Ataxia can be caused by various neurological disorders, such as:
  • a tumor or inflammation in the small brain;
  • multiple sclerosis;
  • a stroke;
  • a congenital (genetic) disorder (ADCA).

A congenital genetic defect

ADCA (Autosomal Dominant Cerebellar Ataxia) is a hereditary and slowly deteriorating (degenerative) disease of the small brain and one of the causes of ataxia. Autosomal means that both the male and female descendants can inherit the disease from the parents. Dominant means that there is a 50% chance of the disease being transferred from parent to child. With ADCA, the nerve cells in the small brain shrink and die over the years (atrophy). The symptoms of the hereditary variant of ataxia usually only manifest themselves in adulthood, around the age of 50. With ADCA, coordination of movement is often the first to be disturbed. In addition, the symptoms with ADCA are:
  • difficult to talk;
  • eye problems;
  • difficulty swallowing with the possibility of swallowing;
  • huge tiredness;
  • impairment of nerve endings in arms and legs.

The wrong gene

The hereditary form of ataxia is caused by a 'wrong' gene. A gene is a piece of DNA that contains the code for a series of amino acids. Amino acids that together ensure the production of proteins, the building blocks of our body. More amino acids (glutamine) are produced at ADCA than normal and this gives protein clotting which causes the nerve cells of the small brain to die, so that they can no longer support the muscles. It is a progressive genetic disease in which scientific research in June 2015 revealed a little more about the cause, namely that the wrong gene is related to a clumping of proteins.

Spinocerebellar ataxia (SCA)

SCA (SpinoCerebellar Ataxia) is the name for the hereditary form of ataxia (ADCA) when the gene with the 'mistake' is known. If research shows which gene is responsible for the disease, ADCA is given the name SCA with a number and is then called ADCA-SCA6, for example. More than thirty types of SCA have been described worldwide, of which seventeen types of SCAs are already known through genetic research. The numbering is in the order in which they were discovered and not the severity of the disease. The 'error' is not always on the same gene and therefore not everyone is equally ill, but there is an overlap in symptoms. Spinocerebellar ataxia (SCA) is therefore a disease of the nerves because the nerves cannot or cannot properly transmit their signals to the muscles. SCA is usually caused by the hereditary disease ADCA but can also be caused by:
  • a vitamin deficiency;
  • alcohol;
  • an infection.

The reason why someone with SCA:
  • walks like a drunk person;
  • unclear talks;
  • write bad;
  • drops things out of your hands.

SCAs are found all over the world and for a number of SCA types remarkable differences in the occurrence have been described per country. People who inherit an SCA from their father or mother often get sick younger than their father or mother. And their children (if they also have the disease) fall ill even younger. That is why it is important that the entire family is tested. The geographical distribution in the Netherlands is largely as follows:
  • SCA3 mainly occurs in the provinces of Groningen and Drenthe.
  • SCA2 mainly comes in families that originate from Friesland.
  • SCA1 and SCA6 are common in the middle and west of the country.

The different types of gene defects and SCAs

In 2000 it was investigated how many families, then known, were in the Netherlands with the different SCAs. The types of SCA that are common in the Netherlands are:
  • SCA1
  • SCA2
  • SCA3
  • SCA6
  • SCA7
  • SCA8

SCA1

The first SCA1 symptoms are speech, swallowing and walking disorders. The course of the disease is serious. Patients end up from a walker in a wheelchair, which eventually leads to premature death. In the Netherlands there were 15 families with SCA1 in the year 2000.

SCA2

Walking, talking and controlling the body becomes difficult and coordination decreases. In the end, breathing and swallowing are also affected, and a slight form of dementia can occur. The eye muscles are also affected. In the Netherlands in 2000 there were fourteen families with SCA2.

SCA3 (or Machado-Joseph's disease (MJD)

Spinocerebellar ataxia type 3 (SCA3), or Machado-Joseph's disease, is most common in the Netherlands. The Machado-Joseph form is characterized by a slow decline of SCA. The range of symptoms is wide and causes the disease to be separated at the age when it starts and the characteristic symptoms. The disease therefore has the following types:
  • Type I
  • Type II
  • Type III
  • Type IV
  • Type V

Symptoms type I

SCA3 type I symptoms develop between the ages of ten and thirty. Symptoms such as muscle tensions in arms and legs, muscle stiffness and coordination and balance problems. Walking is not smooth and seems like a drunken walk, the speech is unclear to unintelligible and swallowing is difficult.

Symptoms type II

Between 20 and 50 years of age, symptoms develop with SCA3 type II with the same symptoms as with SCA type I, but the disease progresses more slowly. The disorder of muscle movements (ataxia) and coordination problems are more prominent in this type.

Symptoms type III

The symptoms of SCA3 type III arise between forty and seventy years. Also with an unsteady gait (the drunken run). An unsteady gait (ataxia) and nerves characterized by recurrent attacks of pain in the shoulder, arm and / or hand, followed by total or partial paralysis of the muscles in these places (amyotrophy) and degeneration of the peripheral nerves . Type III progress is the slowest of the three types.

Type IV

In type IV, symptoms such as Parkinson's disease are mainly symptoms such as:
  • Vibrate.
  • Stiffness of the muscle and balance problems.
  • Lack of automatic movements.

Type V

The symptoms of illness resemble the hereditary condition of spastic paraplegia, a condition of the spinal cord. The symptoms are stiffness and spasticity in the legs.
Especially people with type I and type II may experience difficulties with the eyes such as double vision, blurred vision, no color / or contrast distinguish and not control eye movement. Type IV and V require more research, which is why many researchers only use the first three types.

SCA6

The 'wrong' gene of SCA6 was discovered in 1997. A repeat of a number of proteins on the DNA is the cause. An 'error' protein is formed by this abnormality and this causes the death of certain cells in the small brain. A person with SCA6 has, because fine motor skills are disturbed, a drunken run, speech problems, writing problems, and after a while swallowing problems. Due to the difficult walking, the person will need a walker and after a while a wheelchair. In the Netherlands in the year 2000, twenty-eight families with SCA6 were registered. The condition usually starts around the 50th to 60th year of life, but can also start around the 30th year of life or the 80th year.
Sheffield University in England is starting a study in 2016 to better understand what exactly changes when walking patients with ataxia during the condition.

SCA7

The first symptoms of SCA7 manifest themselves in adulthood. SCA7 is associated with macular dystrophy, a disease of the eyes that reduces vision. Many of the clinical and pathological findings of the other Spinocerebellar Ataxia (SCA) overlap with SCA7. The symptoms of SCA7 manifest themselves earlier and in a more severe form in every generation. This is called genetic anticipation. In the year 2000 there were 16 families with SCA7 in the Netherlands.

Video: Degenerative Spine. Q&A with Dr. Lee Riley (February 2020).

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