Culture

Familial amyloidosis with polyneuropathy


Foto Jan Hofverberg		 Due to the pioneer work of Rune Andersson 1965-76 (1), the Department of Internal Medicine at Umeå University got a swift start in basic research and clinical research on familial amyloidosis with polyneuropathy (FAP). The topic became a national specialty for the Department in 1997. The representative of the specialty, Ole Suhr, was promoted professor of medicine, especially gastroenterology, in 2001.

Ole Suhr was born in Copenhagen 1948. He was trained at Sorö Internat College. He became medical doctor in Copenhagen 1976. By then, he had already served at Swedish hospitals, Bollnäs and Söderhamn. For post-doctoral training toward specialty in internal medicine, he returned to Sweden, Vänersborgs Hospital 1976-81. Then he moved north, to the University of Northern Sweden in Umeå. He became an internist and gastroenterologist and defended his theses 1990. His scientific production reflects the development in the research on FAP (A).

Primary health care and FAP

In primary health care, FAP is a painful surprise for most doctors. It may be confused with early stages of neuropathy due to cobalamin deficiency (cf. Case No 7 of The Rondel), multiple sclerosis, stenosis of the spinal cord, or lumbal disc protrusions.

The hallmark of FAP is the painful progressive polyneuropathy. I feel that the polyneuropathy of cobalamin deficiency is less painful. A patient with B12 deficiency and sensory loss in feet and legs will respond with pain after weeks or months of cobalamin/folate therapy. In such a case, the pain reflects the dawn of heeling – the nerves awake and produce pain again. This pain, often misinterpreted as therapy failure, is more superficial than the previous pain of disease progress.

Although FAP patients are prone to develop nutrient deficiency, they respond rarely and transiently to nutrients. I interprete Case No 7 of The Rondel as a coincidence between a pernicious anemia and later on symptoms of FAP.

The diagnosis of FAP is based on the typical mutation in transthyretin (TTRmeth30), amyloid precipitation in tissues, and clinical symptoms. My message to primary health care is that when a case of peripheral polyneuropathy does not respond to adequate doses of cobalamin and folate in 6-12 months, then send 10 ml of EDTA-coagulated blood to The Laboratory of Clinical Genetics (Att. Prof Gösta Holmgren), University Hospital of Northern Sweden, SE-901 85 Umeå, Sweden, and ask for the FAP mutation. If such a mutation is present, the patient should urgently be investigated for tissue deposits of amyloid. The present treatment of FAP is liver transplantation before nerve lesions have become irreversible.

Current research on FAP thrives in Portugal, Japan and Umeå. The biological basis for this scenario is a subject of historical and cultural debate. The disease was first described by the Portuguese neurologist Corino Andrade (2). The contribution of Rune Andersson was a meticulous description of the disease, from toe to eye, progress of symptoms, involvement of tissues, organs, and systems, inheritance. His over-riding conclusion on heredity still holds true; FAP is inherited as an autosomal dominant trait with varying penetrance (1).

Professor Ole Suhr
ole.suhr@medicin.umu.se
Department of Internal Medicine
University Hospital of Northern Sweden
SE-901 85 Umeå, Sweden

References

  1. Andersson R. Familial amyloidosis with polyneuropathy. A clinical study based on patients living in Northern Sweden. Acta Med Scand 1976, Suppl 590.
  2. Andrade C. A peculiar form of peripheral neuropathy. Familial atypical generalized amyloidosis with special involvement of the peripheral nerves. Brain 1952; 75:408-27.

Published August 14, 2001