Fragile X-associated tremor/ataxia syndrome

The fragile X -associated Tremor-/Ataxiesyndrom ( FXTAS ) is a hereditary neurodegenerative disease. You can attack a carrier called a premutation of the FMR1 gene change.

Classification, incidence, and risk groups

FXTAS is a relatively rare, inherited disorder first described in 2001. It ill far more men than women. The lifetime risk for FXTAS for men is 1:3000 to 1:6000. The average age at diagnosis is 60 years. Approximately 75 % of the over 80 -year-old carrier of the FMR1 premutation - have symptoms of FXTAS.

Symptoms

The main symptoms are ataxia, mainly in the form of gait disturbances, tremors in goal-directed movements (intention tremor), polyneuropathy and the decline in mental abilities through to dementia. The disease may start with one of these symptoms. This complicates the diagnosis.

Some patients develop mild Parkinson's symptoms, blood pressure drop on standing up ( orthostatic hypotension) and disturbances of bladder and bowel function. Anxiety and depression are common.

Men with FXTAS often have testosterone deficiency. In women, menopause can begin before the age of 40. Women with FXTAS often suffer from an underactive thyroid.

Diagnosis

Not all carriers of premutation - FRM1 developing FXTAS. Proof of premutation therefore not sufficient to diagnose a FXTAS. In addition, typical symptoms and typical changes in the magnetic resonance imaging should be available.

Genetics

FXTAS is a result of a change in the FMR1 gene and belongs to the group of trinucleotide repeat disorders:

The FMR1 gene contains in healthy 5-40 repetitions of the three- nucleotide base sequence 5'- CGG -3 '. More than 200 CGG repeats cause the gene loses its function. People with such a high number of repetitions are mentally retarded, they suffer from the fragile X syndrome.

59-200 CGG repeats are referred to as premutation: The genetic material must be copied for the formation of egg or sperm cells. The copying process for the FMR1 gene is disrupted in carriers of the premutation of the gene. The result is that the number of CGG repeats in germ cell formation further increased. The carriers of the premutation while not in themselves affected by fragile X syndrome, but their children can suffer.

The protein FMRP produced by the FMR1 gene premutation met with, although his task. However, apparently it has additional adverse effects. This in the long run to nerve cells damage and disease FXTAS. Support a high number of CGG repeats suffer earlier and heavier FXTAS.

The FMR1 gene is located on the X chromosome. Women have two X chromosomes. The healthy copy of the gene on the second X chromosome is the reason that both FXTAS and fragile X syndrome in women are much less common than in men.

Pathology

In the study of the brain under the microscope ( histology) the presence of small particles in the nucleus ( inclusion bodies ) containing the protein ubiquitin. Especially many of these ubiquitin -positive inclusion bodies lie in the hippocampus.

Treatment

FXTAS can neither be cured nor stopped by treatment. It is possible to relieve some symptoms such as tremor by drugs.