Amyloidosis hereditary E85.2

Group of autosomal-dominantly inherited, rare diseases with clinical and genetic heterogeneity, which leads to deposits of the "waste protein" amyloid in numerous organs The disease is counted among the systemic (primary) amyloidoses. They are summarized under the designation AH or AF.

The classification is based on the amyloid-forming proteins involved in each case:

• Transthyretin amyloidosis (TTR)
  • Familial amyloid polyneuropathy of the Portuguese type (FAP 1)
  • Familial Cardiomyopathy (FAC)
• Apolipoprotein A1 (nephro-,polyndeuro-, hepatopathy)
• Gelsolin (corneal opacities, polyneuropathy)
• Fibrinogen alpha (nephropathy, petechiae)
• Lysozyme (nephropathy)
• Amyloid-beta-precursor protein (hereditary cerebral hemorrhage with amyloidosis - Dutch type)
• Cystatin C (hereditary cerebral hemorrhage with amyloidosis - Icelandic type)
• BRI-precursor protein (Hereditary dementia of the British/Danish type)

Rare group of diseases occurring all over the world. Commonly found in Portugal, Japan, Sweden, Spain, Finland and France. Hereditary systemic amyloidosis affects 5% of the total systemic amyloidosis population.

Occurrence of the disease through mutations of genes coding for the following physiological proteins: most commonly for transthyretin (TTR), a thyroxine-binding prealbumin; more rarely for apolipoprotein A1, lysozyme, gelsolin, amyloid-β, cystatin C, BRI precursor protein and fibrinogen Aα.

In the common TTR amyloidosis: polyneuropathy, carpal tunnel syndrome, impotence, diarrhea, constipation, cardiomyopathy and vitreous opacities.

Less frequently in the presence of other mutations: nephropathy, petechiae and renal insufficiency.

Orthotopic liver transplantation.

Experimental: drug stabilization of the TTR tetramer.

1. Adams D et al (2000) The course and prognostic factors of familial amyloid polyneuropathy after liver transplantation. Brain 123: 1495-1504
2. Almeida MR et al (2000) Screening and biochemical characterization of transthyretin variants in the Portuguese population. Hum Mutat 9: 226-233
3. Buxbaum J (2006) The genetics of the amyloidoses: interactions with immunity and inflammation. Genes and Immunity 7: 439-449
4. Hund E et al (2001) Transthyretinassociated neuropathic amyloidosis. Neurology 56: 431-435