Fragile X-associated tremor / ataxia syndrome

The fragile X-associated tremor / Fragile X syndrome ( FXTAS ) is an inherited neurodegenerative disease . It can affect carriers of a change in the FMR1 gene known as a premutation .

Classification, frequency and risk groups

FXTAS is a relatively rare hereditary disease, first described in 2001. Far more men than women become ill. The lifetime risk for FXTAS for men is 1: 3000 to 1: 6000. The average age of onset is 60 years. Approximately 75% of carriers of the FMR1 prevalence over 80 years of age have symptoms of FXTAS.

Symptoms

The main symptoms are ataxia , mainly in the form of gait disorders, tremors during purposeful movements ( intention tremor ), polyneuropathy and a decline in mental abilities up to dementia . The disease can begin with any of these symptoms. This makes the diagnosis more difficult.

Some patients develop mild Parkinson’s symptoms, a drop in blood pressure when standing up ( orthostatic hypotension ) and disorders of the bladder and bowel function. Anxiety and depression are common.

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

diagnosis

Not all carriers of the FRM1 premium develop FXTAS. Evidence of the premutation is therefore not sufficient to diagnose FXTAS. In addition, typical symptoms and typical changes in the magnetic resonance imaging should be present.

genetics

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

The FMR1 gene contains 5-40 repetitions of the three in healthy nucleotides existing base sequence 5'-CGG-3 ' . More than 200 CGG repetitions cause the gene to lose its function. People with such a high number of repetitions are mentally disabled and suffer from Fragile X syndrome .

59–200  CGG repetitions are known as premutation: the genetic material must be copied for the formation of egg or sperm cells . The copying process for the FMR1 gene is disturbed in carriers of the premutation of this gene. This leads to the fact that the number of CGG repetitions during germ cell formation increases further. The carriers of the premutation are not affected by the fragile X syndrome themselves, but their children can become ill.

The protein FMRP produced by the FMR1 gene with premutation does its job. However, it appears to have additional adverse effects. In the long term, these lead to nerve cell damage and the disease FXTAS. Carriers with a high number of CGG repeats get earlier and more severe with FXTAS.

The FMR1 gene is 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 are much rarer in women than in men.

pathology

Examining the brain under a microscope ( histology ) reveals small particles in the cell nucleus ( inclusion bodies ) that contain the protein ubiquitin . A particularly large number of these ubiquitin-positive inclusion bodies are located in the hippocampus .

treatment

FXTAS cannot be cured or stopped by treatment. It is possible to relieve individual symptoms such as tremors with drugs.

literature

• C. Finke et al. a .: Fragile X-associated tremor / ataxia syndrome. In: Der Nervenarzt , 2009, doi: 10.1007 / s00115-009-2846-6
• G. Shan et al. a .: FXTAS: a bad RNA and a hope for a cure. In: Expert Opin. Biol. Ther. 2008; 8 (3), pp. 249-253. PMID 18294097 , full text (PDF) for registered users of the University of Frankfurt / M.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !