ReviewWhen Should Cardiologists Suspect Anderson-Fabry Disease?
Section snippets
Clinical Scenarios
In each of the following scenarios, the family history and clinical traits in probands and relatives are highly informative for suspecting AFD. A disease-oriented interview is the first low-cost step of the diagnostic workup.
Electrocardiography
Incidental findings of a short PR interval without a d wave (below the lower limit for age in children15, 16 and <120 ms in adults17) in subjects who undergo electrocardiography for cardiac or noncardiac reasons (presurgery evaluation, sport suitability, etc.) should be considered with caution as early potential markers of a myocardial storage disease18 (Figure 2). A short PR interval is seen in 21% to 40% of adult patients with AFD17, 19, 20, 21 and in about 28% of pediatric patients.14 The PR
Differential Diagnosis Between Anderson-Fabry Disease and Sarcomeric Cardiomyopathy
A disease-oriented process of differential diagnosis between sarcomeric and nonsarcomeric HC, including AFD, can be supported by type of inheritance, instrumental markers, and clinical data that may guide biochemical and genetic testing. Table 2 lists the major cardiac and noncardiac traits that may help differential diagnoses.
Genetic Testing and Counseling
Genetic counseling should be performed before genetic testing, according to international guidelines and recommendations for adults and minors.48, 49
In hemizygous men, the fastest and cheapest way to perform the test is by direct automated sequencing of the coding and flanking regions of the gene. The dosage of α-galactosidase activity is usually highly informative. In heterozygous women, assays for detecting heterozygosity followed by automated sequencing of heteroduplex amplicons is the
Treatment of Anderson-Fabry Disease
Since 2001, the availability of ERT has mandated that a correct diagnosis of AFD be made. Two drugs are available: agalsidase alfa and agalsidase beta. The former has had marketing authorization in Europe since 2001 and is undergoing Biologics License Application filing in the United States. The latter has been marketed in the United States and in Europe since 2001. Patients with proved diagnosis of AFD should be informed about ERT, its method and frequency of administration, contraindications,
Conclusions
Cardiologists may play a key role in suspecting and diagnosing AFD. In a disease-oriented mind-set, simple and low-cost tools such as family medical history, electrocardiography, and echocardiography may raise the diagnostic hypothesis. Endomyocardial biopsy is highly contributory, and genetic testing is the gold standard for diagnosis. Although the final decision for treatment is up to patients, the availability of ERT makes the diagnosis mandatory.
Acknowledgment
We are grateful to patients and families for their support in the activities of our center and for their helpful contributions in the critical discussion about their disease during counseling. We are also grateful to Monica Concardi and Anna Liew for their professional support of this study.
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2022, Cardiovascular PathologyAwareness of Fabry disease in cardiology: A gap to be filled
2018, Revista Portuguesa de CardiologiaCitation Excerpt :The ECG abnormalities observed in this analysis are commonly described in patients with LVH, whatever the cause, patients with sarcomeric HCM or FD included. A short PR interval is classically described in 21%-40% of patients with FD,42 particularly in its early stages but, although less common, it is also described in HCM (3.3% in the study population). Likewise, a tendency for PR prolongation and AV block is described in the later stages of FD,43 and these abnormalities may also occur during the natural history of sarcomeric HCM.
Clinical Features, Diagnosis, and Management of Patients With Anderson-Fabry Cardiomyopathy
2017, Canadian Journal of CardiologyCitation Excerpt :Coronary microvascular dysfunction is an important clinical problem in contemporary cardiology and AFD is a stereotypical example of this clinical phenotype.67 Common electrophysiological manifestations of AFD include shortened PR interval (in early stages), atrial fibrillation (in advanced stages), and increased QRS duration.68,69 Electrocardiographic changes can precede the development of LVH or symptoms of cardiovascular disease.27
Genetic Screening of Anderson-Fabry Disease in Probands Referred From Multispecialty Clinics
2016, Journal of the American College of CardiologyAbnormalities of the Mitral Apparatus in Hypertrophic Cardiomyopathy: Echocardiographic, Pathophysiologic, and Surgical Insights
2016, Journal of the American Society of EchocardiographyCardiomyopathies
2016, Cardiovascular Pathology: Fourth Edition
This study was supported by “Ricerca Corrente GIMAF: Gruppo di Studio Interdisciplinare per la Sindrome di Anderson Fabry” from the National Ministry of Health, Rome, Italy, to IRCCS Policlinico San Matteo and by Fondazione Cariplo, Milan, Italy.