DIAGNOSIS OF FABRY’S DISEASE

Males with conventional FD may have an easy diagnosis, whereas females and those with
genetic variations may have a difficult diagnosis.

It is advised to use a comprehensive diagnostic approach that includes a family history, physical
examination, clinical and biochemical findings, genetic testing, expert opinion, and various
imaging procedures. Some clinical findings and signs, such as acroparesthesia, angiokeratomas,
and cornea verticillate, may have a high specificity.

Measurements of α-Gal A activity should be made in males suspected of having FD. When
females have α-Gal A activity within the normal range, even in the presence of clinical signs, it
is highly suggestive of classic FD . The majority of these females go on to develop clinically
significant disese .

Male and female subjects must undergo genetic confirmatory testing. Mutations in the GLA gene
may be linked to the classic FD, a variant phenotype, or a GVUS. We present an updated
diagnostic algorithm in

Figure 1. At the time of FD diagnosis, migalastat amenability for pharmacological chaperone

therapy can be determined using a human embryogenic kidney cell-based in vitro assay validated
by good laboratory practise (GLP).

Figure 1 shows the updated FD diagnostic algorithm. Permission to adapt from van der Tol L,
Smid BE, Poorthuis BJ, et al. is granted. A comprehensive analysis of Fabry disease screening:
the frequency of people with genetic variations of unclear significance. J Med Genet. 2014;51:1–
9. Copyright © 2014, BMJ Publishing Group Ltd. Citation10: Clinical Features, Diagnosis, and
Management of Patients With Anderson-Fabry Cardiomyopathy, Yogasundaram H, Kim D,
Oudit O, Thompson RB, Weidemann F, Oudit GY. Reproduced with permission. Can J Cardiol.
2017;33: 893–897. Copyright 2017 Canadian Heart Society. Citation27 Excerpted with
permission from Thompson RB, Wen K, Putko BN, and colleagues. The frequency,
pathophysiology, diagnosis, and management of Anderson-Fabry cardiomyopathy. (2015) Heart
Fail Rev. 20:179–191. Citation49 Adapted with permission from Laney DA, Bennett RL, Clarke
V, et al. Copyright © 2014, Springer Nature. Guidelines for treating Fabry disease: the National
Society of Genetic Counsellors' guidelines. J Genet Counsellors. 2013;22:554-564. The content
of this page is copyrighted by the National Society of Genetic Counsellors, Inc. (2013).
Citation43: α-Galactosidase A (α-Gal A), α-galactosidase A gene (GLA gene),
globotriaosysphingosine (Lyso-Gb3), left ventricular (LV). Citation48: Data from Niemann et al.
*Punch biopsy, collected to assess Gb3 deposits and for other histological evaluations, from
different lesions or from proximal (thigh: 15 cm above the patella) and distal (leg: 10 cm above
the lateral malleolus) hairy skin sites.

In patients with GVUS, the lyso-Gb3 test can be used to determine whether the mutation is
potentially clinically significant and whether FD should be diagnosed. Lyso-Gb3 has also
emerged as a powerful biomarker for FD, particularly the variable α-Gal A activity and
mutations. Even in the absence of clinical manifestation, Lyso-Gb3 can be utilized to stratify
patients into classic and variant phenotypes. Citation 48 Lyso-Gb3 is particularly useful as a
phenotype discriminative marker due to phenotypic variability, which is most noticeable in
females.

APA citation :
Vardarli, İ., Rischpler, C., Herrmann, K., & Weidemann, F. (2020). <p>Diagnosis
and Screening of Patients with Fabry Disease</p> Therapeutics and Clinical Risk Management,
Volume 16, 551–558. https://doi.org/10.2147/tcrm.s247814