Diagnosis

All patients with suspected or diagnosed ATTR amyloidosis should be assessed in a dedicated specialist unit. In the UK, the referral centre is the NHS National Amyloidosis Centre (NAC) at the Royal Free Hospital, London. Information for referring physicians in the UK is available here.

The Centre for Amyloidosis and Acute Phase Proteins comprises the NHS National Amyloidosis Centre, funded since 1999 by the Department of Health to provide diagnostic and management advisory services for the national caseload of patients with amyloidosis, and the Wolfson Drug Discovery Unit.

Doctors may suspect ATTR amyloidosis on the basis of patients’ symptoms, findings on physical examination and sometimes family history. The diagnosis can be confirmed (or eliminated) by tests including:

1. Tissue biopsy
2. Genetic testing
3. Imaging studies

Tissue biopsy

In this procedure, a small sample of tissue is removed from the body with a needle and examined in the laboratory. The tissue sample is often obtained from under the skin in the stomach area (abdominal fat biopsy). Alternatively, when ATTR amyloidosis is suspected, the biopsy sample may be taken from the heart, a nerve in the arm or leg, or the bowel, depending on the clinical features of the patient. In the laboratory, the tissue sample is examined using specific techniques to identify amyloid fibrils, including staining of the tissue with a dye called Congo red. Positive Congo red staining can identify amyloid. Then immunohistochemistry and proteomics testing can identify TTR fibrils and determine which type of ATTR amyloidosis is present, by distinguishing between ‘variant’ ATTR in hereditary ATTR amyloidosis and ‘wild type’ ATTR in wild type ATTR amyloidosis.

These techniques are discussed in more detail here.

Genetic testing

Genetic testing involves examination of the DNA from the patient’s cells. These tests are performed on blood samples taken from the patient’s vein.

These techniques can identify amyloidogenic mutations (abnormalities) in the TTR gene. There are over 100 known mutations in the TTR gene, and different mutations lead to different types of disease. The precise mutation identified may provide information about the likely clinical course. For example, the most common mutation worldwide, the Val30Met mutation often leads to amyloid deposits just in the nerves, not in the heart.  In contrast, the Val122lle mutation usually leads to amyloid deposits just in the heart, not in the nerves.

In wild type ATTR amyloidosis, amyloid fibril analysis detects ‘wild type’ ATTR protein and genetic testing will not detect any abnormalities in the ATTR gene.

Imaging studies

Imaging studies of the heart including ECG, echocardiogram, DPD scanning and in some cases cardiac MR scanning may give helpful information. These tests are discussed here.

SAP scanning, which helps to show amyloid deposits in organs such as the liver, spleen and kidneys, may not be helpful as it does not show amyloid deposits in the heart or nerves.