TRAM2 Study

TRAM2 Study is a multicenter epidemiological analysis focused on analyzing the prevalence of hereditary transthyretin-related amyloidosis (hATTR) among patients in Germany, Austria and Switzerland.

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Summary and Rationale


TRAM2 Study is a prospective, multicenter study in Germany, Austria and Switzerland focusing on patients with polyneuropathy or cardiomyopathy of undetermined etiology. The aim of the study is to estimate the epidemiological prevalence of hATTR in a population of 5,000 patients with polyneuropathy or cardiomyopathy of unknown etiology.

Study access on CentoPortal® for participating physicians


Study Rationale

hATTR is an autosomal dominant inherited variable penetrance disease that often is under or misdiagnosed, and it is caused by mutations in the receptor gene TTR. Since the TTR gene is responsible for the function of a protein called transthyretin (a tetrameric transport protein that forms amyloid fibrils), due to mutations in the TTR gene, hATTR results in defective protein folding that leads to cytotoxicity in the body. The clinical spectrum of hATTR varies greatly from exclusive neurological involvement to predominant cardiac manifestations, and without treatment hATTR can lead to heart failure.

Patient Benefits

Participating patients receive a definite diagnosis of hATTR. This step has also a direct impact for the majority of the families due to the autosomal inheritance mode. 

Information about the Study

Design: Epidemiological, multicenter, international, and non-interventional study

Study population: Patients with polyneuropathy or cardiomyopathy of undetermined etiology

Number of patients: 5,000 participants

First patient in: April 2018

Last patient in: December 2020

Inclusion period: 24 months


  • Estimation of the prevalence of hATTR in patients with polyneuropathy or cardiomyopathy of undetermined etiology
  • Clinical characterization of patients with hATTR

Find out how you can participate:

Medical Facts

The prevalence of polyneuropathies of any etiology is generally around 2,400 per 100,000 (2.4%). However, among older populations, the prevalence increases to approximately 8,000 per 100,000 (8%). 

In general populations, approximately 50% of patients with heart failure have heart failure with preserved ejection fraction and left ventricular hypertrophy. Heart failure with preserved ejection fraction is a clinical syndrome associated with many risk factors, and results in poor quality of life, substantial use of health-care resources for treatment, and significant premature mortality among patients. 

In an adult, left ventricular hypertrophy is defined by the presence of a left ventricular wall thickness ≥15 mm in one or more left ventricular myocardial segments that is not explained solely by abnormal loading conditions. Five to ten per cent of adult cases are caused by genetic disorders.

hTTPR is a frequently misdiagnosed cause of small fiber polyneuropathy and heart failure with preserved ejection fraction.  

hATTR Disease Facts

hATTR is a fatal illness resulting from autosomal dominantly inherited single-point mutations on the TTR gene. As a result of mutations in the hATTR gene, the wrong folding of the protein called transthyretin makes them insoluble and they can no longer be broken down by the body; resulting protein deposits lead to progressive damage to the body.

This disease typically strikes people in their 30s to 50s and may lead to death within 10 years without treatment.

Neurological manifestations of hATTR include unrelated tingling, pain and numbness in the arms and / or legs, muscle weakness, muscle cramps and paralysis, bladder discomfort, constipation or diarrhea, and even impotence. 

Cardiac manifestations of hATTR include heart failure, shortness of breath, poor performance, palpitations and fluid retention

The diagnosis of TTR-CM remains challenging. The diagnosis strategy for hATTR combines diagnostic imaging, histopathology and molecular genetic testing.

There are specific pharmacological treatments for hATTR patients. The treatment is symptomatic and disease modifying: gene silencing therapies like patisiran (Onpattro, Alnylam Pharmaceuticals, Inc.) and inotersen (Tegsedi, Akcea Therapeutics, Inc.), tetramer stabilization like tafamidis (Pfizer) and diflunisal (several companies).

Study Design

The patients fulfilling the inclusion criteria will be enrolled into the Study. All participants will have a single research blood sample drawn, which will be equivalent to 30 drops of blood (around 1ml). The sample will be applied to a CentoCard®, which will be sent to CENTOGENE and analyzed in CENTOGENE’s laboratory.

The sample will be molecular genetically tested with NGS-based sequencing of the entire TTR gene.

Inclusion Criteria
Informed consent is obtained from the participant
The participant is aged between 18 and 85 years
The participant is diagnosed with cardiomyopathy or polyneuropathy of no obvious etiology
The participant has not undergone chemotherapy for any carcinoma


Sabine Rösner, Project Lead
Am Strande 7
18055 Rostock
Email: sabine.roesner(at)centogene(dot)com

Susanne Zielke, Clinical Research Associate
Am Strande 7
18055 Rostock
Email: susanne.zielke(at)centogene(dot)com

Are you already enrolled in the study and want to log in to your CentoPortal® account?