INTRODUCING

CLASSICAL FABRY DISEASE

Fabry disease is a lysosomal storage disorder caused by variants in the GLA gene and is a progressive, life-threatening, multisystemic condition.

What is classical Fabry disease?

Fabry disease is caused by variants in the GLA gene encoding the enzyme alpha-galactosidase A (α-Gal A).¹Variants in the GLA gene culminating in no or little (<1%) α-Gal A enzyme activity are associated with classical Fabry disease.^1,2

The initial signs of classical Fabry disease typically manifest in childhood. The earliest clinical symptoms of this disease phenotype include acroparaesthesia (tingling, numbness, or pins and needles in the hands or fingers), angiokeratomas (small, non-blanching, dark red or bluish benign skin lesions), heat intolerance, cornea verticillata in the eyes and gastrointestinal symptoms.^3-6 In adulthood, later complications occur as the disease progresses, and may include renal failure, hypertrophic cardiomyopathy, cerebrovascular disease and reduced life expectancy (Figure 1) (see signs and symptoms of Fabry disease).⁶

Peripheral nervous system

Acroparaesthesia; atypical chronic or episodic pain; dizziness; hearing loss; heat and/or cold intolerance; hypohidrosis (impaired sweat function); pain crises; tinnitus; vertigo

Dermatological

Angiokeratomas

Gastrointestinal

Abdominal pain and/or bloating; constipation; difficulty gaining weight in childhood; intermittent diarrhoea; nausea and vomiting

Ophthalmological

Cornea verticillata; cataract; central retinal artery occlusion (rare); conjunctival and retinal vasculopathy; reduced tear secretion

Renal

Pathological albuminuria or proteinuria; decreased glomerular filtration rate progressing to kidney failure

Cardiac

Atrial fibrillation; bradycardia; cardiac fibrosis; cardiomyopathy (particularly hypertrophic cardiomyopathy with concentric hypertrophy and minimal or absent outflow obstruction); chronotropic incompetence; heart failure (mostly with preserved ejection fraction); reduced exercise tolerance; sudden cardiac death; syncope; ventricular tachycardia

Vascular

Aortic stiffness

Cerebrovascular

Cerebral venous thrombosis; cervical carotid dissection; haemorrhagic stroke; ischaemic stroke; transient ischaemic attack

Neuropsychological

Common: anxiety, depression, panic attacks, social adaptive function difficulties

Rare: cognitive decline and dementia

Pulmonary

Dry cough; dyspnoea; sleep-disordered breathing; wheezing

Lymphatic

Lymphoedema in all or part of a limb (also below eyes), pitting oedema

Skeletal

Osteopaenia, osteoporosis

Other

Mild facial dysmorphism

Figure 1.
Clinical manifestations of classical Fabry disease. Reproduced and adapted with permission from Ortiz A et al. Mol Genet Metab 2018; 123: 416-427.⁷

C-ANPROM/INT/FAB/0015; Date of preparation: March 2021

Vardarli I, Rischpler C, Herrmann K, et al. Diagnosis and screening of patients with Fabry disease. Ther Clin Risk Manag 2020; 16: 551-558.
Clarke JT. Narrative review: Fabry disease. Ann Intern Med 2007; 146: 425-433.
The Free Dictionary. Acroparesthesia. Available at: https://medical-dictionary.thefreedictionary.com/acroparesthesia. Accessed November 2020.
Merriam-Webster. Angiokeratoma. Available at: https://www.merriam-webster.com/medical/angiokeratoma. Accessed November 2020.
GP Notebook. Angiokeratoma. Available at: https://gpnotebook.com/simplepage.cfm?ID=-596967355. Accessed November 2020.
Ellaway C. Paediatric Fabry disease. Transl Pediatr 2016; 5: 37-42.
Ortiz A, Germain DP, Desnick RJ, et al. Fabry disease revisited: management and treatment recommendations for adult patients. Mol Genet Metab 2018; 123: 416-427.

Brochure

STRIVING FOR ORGAN PROTECTION
Fabry Disease: Cardiac considerations for diagnosis

Due to the high prevalence of cardiac involvement in patients with Fabry disease, cardiologists are vital in the screening and diagnosis of the disease. Cardiologists are recommended to maintain an awareness of Fabry disease.

Brochure

STRIVING FOR ORGAN PROTECTION
Fabry Disease: Neurological considerations for diagnosis

Neurologists can aid an early diagnosis of Fabry disease and document neurological involvement associated with the disease.

BURDEN OF DISEASE

Late-onset Fabry disease

What is late-onset Fabry disease?

The clinical manifestations of late-onset Fabry disease are variable and may be limited to only one organ. Variants in the GLA gene resulting in residual alpha-galactosidase A (α-Gal A) are associated with this disease phenotype.

Burden of disease

Classical and late-onset Fabry disease: a comparison

What are the differences between classical and late-onset Fabry disease?

The disease course is different between patients with classical or late-onset Fabry disease.

BURDEN OF DISEASE

Genetic inheritance of Fabry disease

How is Fabry disease inherited?

Fabry disease is caused by variants in the GLA gene encoding the lysosomal enzyme alpha-galactosidase A (α-Gal A). There are some key GLA variants associated with the phenotypes of classical and late-onset Fabry disease.

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