Background
Fabry disease
Definite diagnosis of FD
| |
---|---|
Males
|
Females
|
GLA mutation | GLA mutation |
+ | + |
AGAL-A deficiency of ≤5% of mean reference value in leukocytes | normal or deficient AGAL-A in leukocytes |
+ | + |
A or B or C
| |
A | |
≥1 characteristic FD sign/symptom (Fabry neuropathic pain, cornea verticillata or clustered angiokeratoma)* | |
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 mutation | |
Uncertain diagnosis of FD
| |
Males/Females
| |
All patients presenting with a non-specific 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 algorithms**. | |
Gold standard for uncertain FD diagnoses
| |
In subjects with an uncertain FD diagnosis, a GVUS and a non-specific 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 judgment of an expert pathologist, in the absence of medication that can lead to storage, confirms FD. |
Methods
Patients
Consensus procedure
Statistical considerations
Results
Consensus panel
Classes of recommendation
Class I
| Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective | Is recommended/is indicated |
Class II
| Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure | |
Class IIA
| Weight of evidence/opinion is in favour of usefulness/efficacy | Should be considered |
Class IIB
| usefulness/efficacy is less well established by evidence/opinion | May be considered |
Class III
| Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful | Is not recommended |
Overall consensus
Consensus criteria for initiation of ERT
No signs or symptoms
|
Renal*
|
Cardiac*
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CNS*
|
Pain*
|
GI*
| |
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Classical FD, males
| if ≥ 16 years of age (Class IIB) | - microalbuminuria† (Class I) | - cardiac hypertrophy (MWT > 12 mm) without (or only minimal signs of) fibrosis (Class I) | - WMLs (Class IIB) | - neuropathic pain (Class IIA) | GI symptoms (Class IIA if < 16 years of age, Class IIB if > 16 years of age) |
- proteinuria† (Class I) | - TIA/stroke (Class IIA) | |||||
- renal insufficiency (GFR 60–90)# (Class I) | - signs of cardiac rhythm disturbances$ (Class I) | - hearing loss, corrected for age (Class IIB) | - neuropathic pain even if completely controlled (not interfering with daily activities) with pain medication (Class IIB) | |||
- renal insufficiency (GFR 45–60)# (Class IIB) | ||||||
Non-classical FD, males
| - microalbuminuria† (Class I) | - cardiac hypertrophy (MWT > 12 mm) without (or only minimal signs of) fibrosis (Class I) | - WMLs (Class IIB) | - neuropathic pain (Class IIA) | GI symptoms (Class IIA if < 16 years of age, Class | |
- proteinuria† (Class I) | - TIA/stroke (Class IIA) | - neuropathic pain even if completely controlled (not interfering with daily activities) with pain medication (Class IIB) | ||||
- renal insufficiency (GFR 60–90)# (Class IIA) | - signs of cardiac rhythm disturbances$ (Class I) | - hearing loss, corrected for age (Class IIB) | IIB if > 16 years of age) | |||
- renal insufficiency (GFR 45–60)# (Class IIB) | ||||||
Classical FD, females
| - microalbuminuria† (Class IIB) | - cardiac hypertrophy (MWT > 12 mm) without (or only minimal signs of) fibrosis (Class I) | - WMLs (Class IIB) | - neuropathic pain (Class IIA) | GI symptoms (Class IIA if < 16 years of age, Class IIB if > 16 years of age) | |
- proteinuria† (Class IIB) | - TIA/stroke (Class IIA) | - neuropathic pain even if completely controlled (not interfering with daily activities) with pain medication (Class IIB) | ||||
- renal insufficiency (GFR 60–90)# (Class IIA) | - hearing loss, corrected for age (Class IIB) | |||||
- renal insufficiency (GFR 45–60)# (Class IIB) | - signs of cardiac rhythm disturbances$ (Class I) | |||||
Non-classical FD, females
| - microalbuminuria† (Class IIB) | - cardiac hypertrophy (MWT > 12 mm) without (or only minimal signs of) fibrosis (Class I) | - WMLs (Class IIB) | - neuropathic pain (Class IIA) | GI symptoms (Class IIA if < 16 years of age, Class IIB if > 16 years of age) | |
- proteinuria† (Class IIB) | - TIA/stroke (Class IIA) | - neuropathic pain even if completely controlled (not interfering with daily activities) with pain medication (Class IIB) | ||||
- renal insufficiency (GFR 60–90)# (Class IIB) | - hearing loss, corrected for age (Class IIB) | |||||
- renal insufficiency (GFR 45–60)# (Class IIB) | - signs of cardiac rhythm disturbances$ (Class I) |
Consensus criteria to stop or not start ERT
Stop criteria
|
Class of recommendation
|
---|---|
Non-compliance > 50% of infusions | Class I |
Failure to attend regularly (according to local guidelines) at FU visits | Class I |
Persistent life threatening or severe infusion reactions that do not respond to prophylaxis, e.g. anaphylaxis | Class I |
Patient request | Class I |
End stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV) | Class IIA |
End stage FD or other comorbidities with a life expectancy of < 1 year | Class IIB |
Severe cognitive decline of any cause | Class IIB |
Lack of response for 1 year when the sole indication for ERT is neuropathic pain while receiving maximum supportive care* | Class IIB |
Criteria for not starting ERT
|
Class of recommendation
|
Advanced cardiac disease with extensive fibrosis [37] if cardiac disease is the sole treatment indication†
| Class I |
End stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV) | Class IIA |
End stage FD or other comorbidities with a life expectancy of < 1 year | Class IIB |
Severe cognitive decline of any cause | Class IIB |