Adams et al. TTR-FAP Article 2_Diagnosis and TreatmentSupplementary material

Supplementary material.

Table S1. Expert participants of the European Network for TTR-FAP (ATTReuNET) 2012 and 2014

Expert / Speciality / Country / Town
centre / National Reference Centre / For FAP or amyloidosis / National network
Teresa Coelho / Neurology / Portugal / Porto / Yes / FAP / -
Ole B. Suhr / Internal medicine,
gastroenterology / Sweden / Umeå / Yes / FAP / -
David Adams / Neurology / France / Paris / Yes / FAP / +
Michel Slama / Cardiology / France / Clamart / Yes / FAP / +
Laura Obici / Internal medicine / Italy / Pavia / Yes / Amyloidosis / +
Ernst Hund / Neurology / Germany / Heidelberg / Yes / Amyloidosis / +
Bouke P. Hazenberg / Internal medicine, rheumatology / The Netherlands / Groningen / Yes / Amyloidosis / +
Jan B. Kuks / Neurology / The Netherlands / Groningen / Yes / Amyloidosis / +
Juan Buades / Internal medicine / Spain / Palma de Mallorca / No / FAP / -
Josep M. Campistol / Nephrology / Spain / Barcelona / No / Amyloidosis / -
Lucía Galán / Neurology / Spain / Madrid / No / FAP
Theodore Kyriakides / Neurology / Cyprus / Nicosia / Yes / FAP / -
Yesim Parman / Neurology / Turkey / Istanbul / Yes / FAP / +
Ivailo Tournev / Neurology / Bulgaria / Sofia / Yes / FAP / -
Velina Guergueltcheva / Neurology / Bulgaria / Sofia / Yes / FAP / -

ATTReuNET, European Network for TTR-FAP; FAP, familial amyloid polyneuropathy; TTR-FAP, transthyretin familial amyloid polyneuropathy.

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Adams et al. TTR-FAP Article 2_Diagnosis and TreatmentSupplementary material

Table S2. The most importantlaboratories for molecular diagnosis according to Reference Centres and TTR-FAP experts

Country / Molecular biologylaboratory / Genetics department / Analysis
Portugal / Unidade de Genética Molecular,Departamento de Genética
Centro de Genética Médica Jacinto Magalhães (CGMJM), Centro Hospitalar do Porto / Molecular Genetics Unit / Molecular diagnosis of familial amyloid polyneuropathy and familial amyloidosis finnish type (TTR and GSN genes)
GENOMED, Diagnósticos de Medicina Molecular,Instituto de Medicina Molecular –Faculdade de Medicina da Universidade de Lisboa / Molecular Medicine Diagnostics / Molecular diagnosis of familial amyloid polyneuropathy (TTR gene)
Sweden / Department of genetics and pathology, Rudbeck Laboratory, Uppsala University Hospital / Department of Genetics and Pathology / Immunohistochemical diagnosis of amyloidoses
Department of Clinical Genetics,
Umeå University Hospital / Clinical Genetics / Molecular diagnosis of hereditary transthyretin amyloidosis (TTR gene sequencing)
France / Laboratoire de génétique moléculaire, Pharmacogenetics and Hormonology, GHU Paris-Sud, Hôpital de Bicêtrea / Molecular Genetics Laboratory / Molecular diagnosis of familial amyloid polyneuropathy (TTR and GSN genes)
Service de biochimie et génétique moléculaire, Biologie, Pharmacie, Pathologie, CHU Paris Centre –Hôpital Cochin / Biochemistry and Molecular Genetics Service / Molecular diagnosis of familial amyloidosis (B2M, TTR, APOA1, APOA2, FGA, GSN, SAA1, and LYZ genes)
Italy / Laboratorio di Genetica Molecolare, U.O. e Sezione di Genetica Medica, A.O.U. di Ferrara –Polo Chimico-Bio-Medico / Laboratory of Molecular Genetics / Molecular diagnosis of familial amyloid polyneuropathy (TTR gene)
Laboratorio di Biotecnologie e Tecnologie, Biomediche, Centro per lo Studio e la Cura delle Amiloidosi Sistemiche,Fondazione IRCCS Policlinico San Matteo / Laboratory of Biotechnology and Biomedical Technology / Molecular diagnosis of amyloidosis (TTR, APOA1, fibrinogen, lysozyme, gelsolin, and APOA2 genes)
The Netherlands / Sectie Genoomdiagnostiek, Afdeling Medische Genetica, Universitair Medisch Centrum (UMC) Utrechta / Section Genome Diagnostics / Molecular diagnosis of transthyretin amyloidosis (TTR gene)
Laboratorium DNA Diagnostiek,Afdeling Genetica,Universitair Medisch Centrum Groningen (UMCG)a / DNA Diagnostics / Molecular diagnosis of familial amyloid polyneuropathy (TTR, apoA1 and fibrinogen genes)
Germany / Molekulargenetisches Labor, Institut für Humangenetik am Universitätsklinikum Heidelberga / Molecular Genetic Laboratory / Molecular diagnosis of familial amyloidosis (APOA1, FGA, and TTR genes)
Institut für Pathologie des UKSH und der CAU zu Kiel, Universitätsklinikum Schleswig-Holstein –Campus Kiel / Institute of Pathology / Histological and molecular diagnosis of amyloidosis
Spain / Sección de Genética (H. Son Espases), Hospital Universitario Son Espases / Genetics / Molecular diagnosis of transthyretin-related amyloidosis (TTR gene)
Laboratorio de Inmunogenética, Servicio de Inmunologia, Hospital Clínic de Barcelona / Immunogenetics / Molecular diagnosis of familial amyloid polyneuropathy (TTR gene)
Cyprus / Neurogenetics Department, Cyprus Institute of Neurology and Genetics (CING) / Neurogenetics Department / Molecular diagnosis of familial amyloidosis (TTR gene)
Bulgaria / Medico-diagnostic Lab ‘Genika’, Sofia / Genetics / Molecular diagnosis of familial amyloidosis (TTR gene)
Turkey / Institute of Experimental and Medical Research, Istanbul Universitya / Department of Molecular Biology and Genetics / Molecular diagnosis of familial amyloidosis (TTR gene)
Neuropathology and Neuromuscular Disorders Laboratory, Neurology Department, Istanbul Faculty of Medicine, Istanbul Universitya / Neurology Department / Neuropathology investigations of amyloidosis

GSN, gelsolin;TTR, transthyretin; TTR-FAP, transthyretin familial amyloid polyneuropathy.aAccredited.

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Adams et al. TTR-FAP Article 2_Diagnosis and TreatmentSupplementary material

Table S3. European Expert (ATTReuNET) pre-meeting questionnaire 2012 and 2014

Questions
1. The structure for care of rare diseases and TTR-FAP in your country
Is there a Rare Disease Plan in your country?
Are there identifiable expert/reference centres for the management of amyloid disease in your country?
Is there a specific professional society/group focused on amyloid-associated disease in your country?
Are there identifiable expert/reference centres specifically for the management of TTRFAP in your country?
Are there regional centres for the management of TTRFAP in your country?
Is there a specific TTRFAP patient support group in your country?
Approximately how many diagnosed TTR-FAP patients are there in your country?
Approximately how many people have been identified as carriers of a TTR gene mutation in your country?
Please give a broad picture of your patient cohort over the past 3 years
2. Diagnosing TTRFAP
For the diagnosis of TTRFAP, which types of biopsy are performed in your centre (in priority order with % use for each)?
What are the three most common genetic mutations associated with TTR-FAP in your patients and what percentage of your total patients do they represent?
How many mutations associated with TTRFAP have been identified in your country?
Do you routinely encourage genetic counselling to family members of diagnosed TTR-FAP patients?
Do you have access to specific expert genetic counsellors in your centre?
3. Management of patients diagnosed with TTR-FAP and funding
What is the mean waiting time for a TTRFAP patient before liver transplant?
Is funding of care for TTR-FAP patients an issue in your country?
Do people with a diagnosis of TTR-FAP receive specific social benefits/social security in your country?
4. On-going care of TTR-FAP patients and asymptomatic carriers
For how long do you typically manage a TTRFAP patient in your centre?
How frequently does a TTR-FAP patient visit your clinic for routine follow up?
How many specialists will a TTR-FAP patient see at each follow-up visit?
Which investigations and tests do you undertake at a routine review of TTR-FAP patients?
Which investigations and tests do you undertake at a routine review of asymptomatic carriers?
How frequently does an identified asymptomatic carrier of a TTR mutation visit your clinic for routine follow up?
5. The typical ‘patient journey’ in your country
In your experience, how many different physicians does the typical TTR-FAP patient see prior to achieving an accurate diagnosis?
In your experience, what would you estimate is the average amount of time between symptom onset and accurate diagnosis of TTR-FAP?
In your experience, what is the typical ambulatory status of patients at diagnosis of TTR-FAP (stage and proportion %)?
6. Further considerations
Which factors in the current management of TTR-FAP in your country do you think work well?
Which factors in the current management of TTR-FAP in your country do you think could be improved?
What do you feel are the barriers to optimal diagnosis and care of TTR-FAP patients in your country?

ATTReuNET, European Network for TTR-FAP; TTR, transthyretin; TTR-FAP, transthyretin familial amyloid polyneuropathy.

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