Familial Primary Systemic Amyloidosis: An Experimental, Genetic and Clinical Study1
Journal of Investigative Dermatology
Familial primary systemic amyloidosis, a relatively unrecognized facet of the amyloid problem, represents an unusual disease process with protean manifestations. Genetic, clinical and pathological data with reference to this entity has beea confirmed in four case reports in the world literature (1-4). Maxwell and Kimball (1), on the basis of autopsy findings in three middle aged brothers, submitted the first report alluding to the familial aspect of systemic amyloidosis. The clinical data in
... se cases was not remarkable nor were the genetic implications discussed by these workers. Ostertag (2) in 1950 reported autopsy-proven amyloidosis on two brothers ages 35 and 39. There was suggestive clinical evidence that the mother of these patients and a daughter of them were afflicted with a similar process. Andrade (3) in 1952 described a bizarre disease occurring endemically in the Oporto Region of Portugal. Locally it was known as "Mal dos peinhos" (foot disease). This insidious and relentless affliction was characterized by an essentially universal neurologic involvement. Paresis, particularly of the lower extremities, was a common finding. There was early impairment of thermal and pain sensitivities predominantly in the lower extremities. Gastroenteric disorders (flatulence, constipation, diarrhea) represented a distressing complication. Sexual disturbances in the male were the earliest and most constant complaints in the cases studied. The disease began in the second and third decades with an apparent predilection for males. In a number of cases gradual deterioration and death occurred in seven to ten years. Fifty-one of sixty-four cases reported were familial: ten families were genetically independent, two families were related, while thirteen cases were isolated and unrelated. While a large part of this material represents clinical and laboratory data, autopsies of two cases revealed definite histopathologic evidence of primary systemic amyloidosis. Kantarj ian and DeJong (4) added further genetic, clinical and pathological data to this entity. A father and two daughters were studied with positive necropsy findings in the father and one of the daughters. The syndrome described was not unlike that of Andrade (3) and consisted of neurologic signs and symptoms compatible with a severe progressive peripheral ncuropathy, gastrointestinal symptomatology, and cardiovascular involvement. These workers further expanded the clinical spectrum in that they found endocrine abnormalities consisting of thyroid enlargement, low basal metabolic rate, amenorrhea, and impotence in the male. Remarkable ocular findings consisting of retinal exudates and exophthalmos were also described. On the basis of their genetic data they assumed the inheritance pattern to be a simple dominant.