Table A1.
Diagnostic criteria for a definite diagnosis of FD
| Definite diagnosis of FD | |
|---|---|
| Males | Females |
| GLA variant | GLA variant |
| + | + |
| αGalA deficiency of ≤5% of mean reference value in leukocytes | Normal or deficient αGalA in leukocytes |
| + | + |
| A or B or C | |
| A: | |
| ≥1 Characteristic FD sign/symptom (Fabry neuropathic pain, cornea verticillata or clustered angiokeratoma)a | |
| B: | |
| An increase of plasma (lyso)Gb3 (within range of males with definite FD diagnosis) | |
| C: | |
| A family member with a definite FD diagnosis carrying the same GLA variant | |
| Uncertain diagnosis of FD | |
| Males/females: | |
| All patients presenting with a nonspecific FD sign (such as LVH, stroke at young age, proteinuria) who do not fulfil the criteria for a definite diagnosis of FD have a GLA GVUS. Further evaluations are needed, following diagnostic algorithmsb | |
| Gold standard for uncertain FD diagnoses | |
| In subjects with an uncertain FD diagnosis, a GVUS and a nonspecific FD sign, the demonstration of characteristic storage in the affected organ (e.g. heart, kidney, aside from skin) by electron microscopy analysis, according to the judgement of an expert pathologist, in the absence of medication that can lead to storage, confirms FD | |
Adopted from Smid et al. with permission (Smid et al. 2014)
GLA α-galactosidase A gene, αGalA α-galactosidase A enzyme, GVUS genetic variant of unknown significance
aFabry neuropathic pain meets the “characteristic clinical criteria” if there is neuropathic pain in hands and/or feet, starting before age 18 years, or increasing with heat, fever. Quantitative sensory testing (QST) reveals an increased cold detection threshold and the intraepidermal nerve fibre density is decreased. There is no other cause for neuropathic pain. Angiokeratomas meet the “characteristic clinical criteria” if they are clustered and present in characteristic areas: bathing trunk area, lips and umbilicus. There is no other cause for angiokeratoma. Cornea verticillata meets the “characteristic clinical criteria” if there is a whorl-like pattern of corneal opacities. There is no other cause (medication induced, among others: amiodarone, chloroquine)
bFor organ-specific algorithms, see Smid et al. (2014) for heart and Van der Tol et al. for kidney (van der Tol et al. 2015) and Van der Tol et al. for brain (van der Tol et al. 2014a)