Current guidelines for disease
progression monitoring

Complete history and physical examination including family history and evaluation of quality of life, gastrointestinal symptoms, work/study performance, level of depression/anxiety

Every clinic visit

α-Gal A enzyme activity and GLA mutation analysis.

If not previously determined

Renal Glomerular filtration rate (measured GFR [preferred] or estimated [eGFR] using appropriate formulae)

Annually if low risk, every 6 months if moderate risk, and every 3 months if high to very high risk; a measured GFR only once yearly because of complexity

Albuminuria (preferred, more sensitive) and/or proteinuria (24-h or spot urine for total protein/creatinine and albumin/creatinine ratios)

Annually if low risk, every 6 months if moderate risk, and every 3 months if high to very high risk

25 OH vitamin D

As clinically indicated; vitamin D levels in late fall/early winter

Kidney biopsy

As clinically indicated. Podocyte foot process effacement may precede pathological albuminuria

Blood pressure and cardiac rhythm

Every clinic visit

ECG and echocardiography

Annually, and as clinically indicated

48-h Holter monitoring to detect intermittent rhythm abnormalities; implantable loop recorder recommended for patients with significant hypertrophic cardiomyopathy

Annually, but may be assessed more or less frequently depending on age and other risk factors; if arrhythmias detected, more frequent/detailed rhythm surveillance should be instituted (schedule determined individually)

Cardiac MRI with gadolinium

If available, whenever there is evidence of clinical progression of disease or regularly at an interval > 2 years

Cardiac MRI with T1 mapping

Investigational tool, should be interpreted with caution

Brain natriuretic peptide

At least annually for patients with cardiomyopathy or bradycardia

Brain MRI (TOF MRA at first assessment in male patients aged over 21 and female patients over 30, then according to the clinical picture)

Every 3 years and when clinically needed (e.g., presence of neurological changes that could potentially relate to stroke)

CT imaging

In case of acute stroke and only if MRI is contraindicated due to cardiac pacing

Pain evaluation and history: pain measurement scale such as the Neuropathic Pain Symptom Inventory or Brief Pain Inventory

Annually

Cold and heat intolerance, vibratory thresholds (quantitative sensory testing, if available)

Annually (less frequently in older patients)

Autonomic symptom evaluation by orthostatic blood pressure

Annually

Skin biopsy (for IENFD assessment, if available)

Consider

Audiometry [17]

As required [17]

Spirometry, including response to bronchodilators, treadmill exercise testing, oximetry, chest X-ray

Every 2 years or more frequently for clinical indications; chest X-ray according to clinical indications

Referral to gastroenterology specialist for endoscopic or radiographic evaluation

If symptoms persist or worsen despite treatment

Plasma and urinary sediment lyso-GL-3, GL-3

At baseline and then annually (at the moment, this is for research purposes only); biobanking of plasma/serum samples recommended if feasible

Bone dual-energy X-ray absorptiometry (DEXA)

Consider

Ophthalmological screening

Ophthalmological screening as clinically indicated