In systemic hereditary ATTR amyloidosis neuropathy is frequently observed. Neuropathy can manifest itself as peripheral polyneuropathy or autonomic neuropathy. In peripheral polyneuropathy sensory changes can be felt in the soles of the feet and in the toes with a slow progression upwards in the lower limbs. Often diminished feeling sensation, tingling, decreased perception of hot and cold, shooting pain, and loss of muscle strength. In the hands carpal tunnel syndrome may also be part of a neuropathy, but it is more frequently a sign of entrapment neuropathy (e.g. as consequence of synovial deposition of amyloid in the carpal tunnel). Autonomic neuropathy is caused by involvement of the autonomic nervous system. As a consequence blood pressure can drop sharply from supine to prone position (orthostatic hypotension), resulting in complaints of dizziness. Other manifestations are impotence, incontinence, voiding problems, diarrhoea or constipation, bowel motility disturbances, changed sweating, dry mouth, and dry eyes. Bowel complaints may sometimes result in severe loss of weight.
Not only nerves, but also heart, kidneys, and eyes can be affected. In the heart conduction problems (blocks) are frequently the first manifestation of cardiac involvement, but also cardiac failure (often right sided) can be seen. Arrhythmia is another manifestation. Kidney function may be decreased and sometimes proteinuria is present. Many different eye problems can be seen, but vitreous opacities are very characteristic of ATTR amyloidosis.
In The Netherlands at least fifteen different families have been detected with a TTR mutation. In nine families the world-wide observed TTR-met30 mutation has been found. Other types are TTR-glu47, TTR-ala71, TTR-89K, TTR-ala94, TTR-cys114, and TTR-122ile. One unknown TTR mutation has been found in a patient, but at that time it was not possible to characterise the specific mutation.
There is also an acquired type of ATTR amyloidosis, found at high age (especially older than 80 years) in which the normal wild type precursor protein transthyretin (TTR) is the characteristic protein. This is clinically characterised by a slowly progressive cardiomyopathy.
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