Familial amyloid polyneuropathy type I

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Classification according to ICD-10
E85.1 Heredofamily Neuropathic Amyloidosis -

Amyloid polyneuropathy (Portuguese type)

ICD-10 online (WHO version 2019)

The familial amyloid polyneuropathy (FAP) is a rare inherited systemic, peripheral neuropathy due to deposition in the tissue ( amyloidosis ) and belongs to the family amyloid polyneuropathy .

Synonyms

Wohlwill-Andrade Syndrome; Corino de Andrade's illness; English Transthyretin-related hereditary amyloidosis, transthyretin amyloidosis (ATTR) .

The name refers to the author of the first description from 1942 by the German neuropathologist Friedrich Wohlwill (1881-1958) and a report from 1952 by the Portuguese neurologist Mário Corino da Costa Andrade .

genetics

The disease is based on mutations in the transthyretin (TTR) gene at gene location 18q12.1. Inheritance is autosomal dominant . If one of the parents is ill, there is a 50% chance that the child will be passed on.

Frequency and age of onset

The disease is most common in Portugal . There the occurrence is limited to a few cities in the north ( Póvoa de Varzim , Vila do Conde ). An increased incidence can also be observed in northern Sweden .

In 80% of the sick, the disease manifests itself within the 20th to 40th year of life . An initial manifestation after the age of 50, however, is rare and often shows an atypical course.

Symptoms

Sensory:
Familial amyloid polyneuropathy often begins symmetrically on the feet in the form of paresthesia and dysesthesia . In the further course of the disease , muscular atrophies , malum perforans and neuropathic joint deformations (Charcot joint) occur. The disease spreads in an ascending manner from the lower extremity. Consequently, the upper extremity is also affected later.
Motor:
In the course of the disease there is paralysis and atrophy of the muscles, initially distal on the lower extremities. For example, the peroneal nerve is paralyzed , resulting in the affected patient's stepping step. In the further course, the upper extremities are also affected, which can be seen, for example, in the development of a clawed hand (ulnar paralysis) .
Vegetative:
The vegetative symptoms often appear initially. It can be observed more frequently in patients who suffer from FAP particularly early on. A wide variety of organ systems are affected. For example, sphincter insufficiency , disorders of the gastrointestinal tract , cardiovascular diseases, renal involvement, eye diseases , skin manifestations and sexual dysfunctions occur .

Diagnosis

The suspicion of the disease can be made on the basis of a neurological examination with a family history. This is followed by a molecular examination of chromosome 18 , in which the typical TTR gene change can be determined.

treatment

One treatment option is a liver transplant . Since the liver is the main synthesis site for transthyretin , no genetically modified transthyretin can be detected in the serum after a liver transplant.

The European Medicines Agency has approved the drug tafamidis for the treatment of FAP. Tafamidis stabilizes the transthyretin tetramer, which should prevent it from breaking down into monomers, which in turn should prevent the formation of fibrils.

literature

  • Sinapse Publication on Familial Amyloid Polyneuropathy published by the Portuguese Society of Neurology (PDF; 2.5 MB)
  • L. Obici, G. Merlini: An overview of drugs currently under investigation for the treatment of transthyretin-related hereditary amyloidosis. In: Expert opinion on investigational drugs. Vol. 23, No. 9, September 2014, pp. 1239-1251, doi: 10.1517 / 13543784.2014.922541 , PMID 25003808 (Review).
  • Y. Ando, ​​T. Coelho, JL Berk, MW Cruz, BG Ericzon, S. Ikeda, WD Lewis, L. Obici, V. Planté-Bordeneuve, C. Rapezzi, G. Said, F. Salvi: Guideline of transthyretin- related hereditary amyloidosis for clinicians. In: Orphanet Journal of Rare Diseases. Vol. 8, 2013, p. 31, doi: 10.1186 / 1750-1172-8-31 , PMID 23425518 , PMC 3584981 (free full text) (review).

Individual evidence

  1. ↑ Amyloidosis, familial, Finnish type. In: Orphanet (Rare Disease Database).
  2. ↑ F. Wohlwill: Formas atipicas since amiloidose. Amatus Lusitanus, Lisboa, 1942, Vol. 1, pp. 373-391.
  3. ^ CM Andrade: A peculiar form of peripheral neuropathy: Familial atypical generalized amyloidosis with special involvement of peripheral nerves. In: Brain, Oxford, 1952, vol. 75, pp. 408-427.
  4. ↑ Who named it
  5. ↑ amyloidosis, hereditary, transthyretin-related.  In: Online Mendelian Inheritance in Man . (English)

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