Wednesday, September 18, 2013

Article Review (1982) - Familial Amyloidosis of Ostertag

Today's post will be a short article review on another previously reviewed article that I recently acquired. This article is from 1982 and it was briefly mentioned in the March 5, 2013 post.

Title: Familial Amyloidosis of Ostertag (1)

Authors: Lanham, Meltzer, De Beer, Hughes and Pepys (yes, that Pepys)

Journal: QJM: An International Journal of Medicine (1982)


A 23 year old Englishman presented with keratoconjunctivitis sicca and was found to have systemic amyloidosis. Five members of his family in two generations also had non-neuropathic amyloid particularly affecting the kidneys. This conforms to the Ostertag type of hereditary amyloidosis. Amyloid deposits in the proband showed permanganate-sensitive Congophilia and positive immunofluorescence staining for P component, but were negative for amyloid A and prealbumin. These observations suggested that the fibril protein in this patient was immunochemically distinct from the amyloid fibrils characterized hitherto.

This article describes yet another kindred with several family members who presented with renal amyloidosis, in which the amyloid appears to be different than that found in AL amyloidosis. The article states this family is the third one reported to have what was referred to at the time as the Ostertag type of familial renal amyloidosis. (Ostertag first published an article describing it in 1950.)

Although the symptoms of these patients are similar to those of fibrinogen amyloidosis patients, I will go ahead and spoil the ending and reveal that these patients did not have fibrinogen amyloidosis. This family was eventually found to have a lysozyme mutation, which was discovered in 1993. This article is actually the first published clinical description of that mutation. It still has some importance in the history of fibrinogen amyloidosis, since it was published at a time when these forms of familial amyloidosis that primarily affects the kidneys (with no neuropathy) were first being described.

Here is a description of each of the six cases from this family described in the article. The 23 year old patient described in the abstract is actually Case 6.

Case 1:  An aunt of Case 6 who died of renal failure at the age of 43.

Case 2:  An aunt of Case 6 who died of renal failure at the age of 38. Autopsy results showed amyloid deposits in the kidneys, spleen, lungs and liver.

Case 3:  Father of Case 6. He presented with hypertension and renal failure at the age of 33 and died three months later in renal failure. Autopsy results showed extensive amyloid deposits in the kidneys, adrenals and spleen. Amyloid to a lesser extent was found in the lungs and the liver.

Case 4:  Male cousin of Case 6. He presented at the age of 33 with hypertension and declining renal function, and started dialysis at the age of 41. A lung biopsy at that time showed amyloid deposits. At the age of 49 he had a kidney transplant but died shortly afterward due to complications. Autopsy results showed extensive amyloid deposits in the kidneys, and to a lesser extent in the lungs, liver, heart, duodenum and pylorus.

Case 5:  Female cousin of Case 6, sister of Case 5. She presented at the age of 45 with hypertension and some renal impairment. Kidney biopsy shows widespread amyloid deposits, but as of the publication of this article she was not on dialysis.

Case 6:  This patient was 23 years old when he presented with a three year history of keratoconjunctivitis sicca (dry eye syndrome). Biopsies of the lip, rectum and kidney showed extensive amyloid deposits. The kidney biopsy did show amyloid deposits in the glomeruli, which is consistent with what is seen in the kidney biopsies of patients with fibrinogen amyloidosis. Additional testing was done on the kidney biopsy tissues which showed the amyloid was not of the AL type.

The two main differences between these cases (now known to be a lysozyme mutation) and the cases of fibrinogen amyloidosis are the age of onset (and death) and the number of different organs affected. For the patients in this article, the ages of onset that we know of ranged from 23 to 45, and the ages of death ranged from 33 to 49. Those ages are considerable younger than the normal range of fibrinogen amyloidosis patients.

The number of different organs affected, especially at such young ages, is something else that is typically not found in fibrinogen patients. Although there are published reports of fibrinogen amyloidosis patients having amyloid deposits in other organs, these are typically only found long after a patient has presented with renal impairment. The lysozyme patients described in this article seemed to have amyloid deposits in multiple organs either when they initially presented (in their thirties or forties) or within a few years.

So once again the authors knew these patients had a different type of familial amyloidosis that primarily affected the kidneys and whose biochemical origin had yet to be discovered. Given what we know now about the fibrinogen and lysozyme mutations, we can see the differences between the two based on the clinical descriptions.

Next up: A milestone

[Edit 11-13-13: Corrected typo in first paragraph after Case 6 description.]


(1) Lanham, J. G., M. L. Meltzer, F. C. De Beer, G. R. V. Hughes, and M. B. Pepys. 1982. Familial amyloidosis of Ostertag. Q. J. Med. 201:25-32.

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