About Fabry disease

Fabry disease is a lysosomal storage disorder caused by deficiency of the enzyme α-galactosidase A, leading to accumulation of glycosphingolipids, particularly globotriaosylceramide, in various cell types throughout the body.

Fabry signs and symptomsJourney through progressions of the diseaseMonitoring Fabry disease

Understanding Fabry disease

Fabry disease is a lysosomal storage disorder caused by deficiency of the enzyme α-galactosidase A, leading to accumulation of glycosphingolipids, particularly globotriaosylceramide, in various cell types throughout the body.

 

This can result in multisystem disease, mainly affecting the kidneys, heart, and nervous system.1 Fabry disease can impact many different organ systems in many different ways.1 Patients may experience a unique combination of symptoms – even in members of the same family, you may see patients with a different presentation of the disease.2,3 This variability can make Fabry difficult to diagnose.3,4

 

 

Fabry signs and symptoms

Neurological

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  • Neuropathic pain
  • Pain crises
  • Hearing loss or tinnitus
  • Hypohydrosis
  • Vertigo or dizziness

Ophthalmologic

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  • Cornea verticillata

Pulmonary

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  • Dyspnea

Cardiac

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  • Arrhythmia
  • Cardiomyopathies
  • Bradycardia
  • Atrial fibrillation
  • Reduced exercise tolerance

Gastrointestinal

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  • Dyspepsia
  • Nausea, vomiting, or intermittent diarrhea and constipation
  • Abdominal pain and/or bloating

Renal

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  • Proteinuria
  • Albuminuria

Lymphatic

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  • Lymphedema

Dermatologic

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  • Angiokeratomas

Taking action

  • Limitations in how we currently measure success for patients with Fabry disease
  • Improving multidisciplinary care for patients
  • Helping your patients navigate their care team

Journey through progression of the disease

Fabry disease may be described in 2 ways:1

  1. Severe, classical phenotype, most often seen in men without residual enzyme activity1
  2. Nonclassical FD, also referred to as late-onset or atypical FD, characterized by a more variable disease course, in which patients are generally less severely affected and disease manifestations may be limited to a single organ1

Early symptoms of Fabry disease typically begin in childhood – often appearing earlier in males than females.4 With age, progressive damage to vital organ systems develops in both genders, leading to organ failure.4

It is important to remain aware that clinical vigilance and regular monitoring are essential, as an absence of symptoms at baseline or at follow-up assessment does not preclude subsequent development of organ complications.2

 

Early intervention and ongoing disease monitoring

The need for prompt and accurate diagnosis of this devastating, progressive disease is paramount so that patients can be identified and treated before irreversible organ damage occurs.3 End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit life-expectancy of untreated patients.4

Renal dysfunction
can progress to kidney failure.3

Cardiovascular manifestations
may eventually lead to heart failure.3

Cerebrovascular manifestations
include early stroke and transient ischemic attacks.3

Disease complications and pain
both negatively influence quality of life.5

Long-term management of adult patients with Fabry disease should involve timely treatment and regular assessment of disease progression in all patients.2

Monitoring Fabry disease

Fabry disease can be monitored through a variety of laboratory tests and patient-reported outcomes.

  • While taking the medical history, inquire about manifestations suggestive of neurologic or cardiac symptoms.
  • Psychological follow-up can provide supportive aid for expression of emotions and feelings involved in the acceptance process and adherence to treatment.

Starting treatment as early as possible may help prevent disease progression—and irreversible organ damage.3

The past decade has witnessed an increased understanding of the pathogenesis, natural history, and prevalence of Fabry disease, and the effectiveness and limitations of specific treatments.2 The advances have changed our approach to disease monitoring and therapeutic intervention, leading to updated Fabry disease treatment guidelines.2

As our understanding of Fabry disease grows, is it time to rethink what’s possible for patients?

References

  1. Arends M, et al. J Am Soc Nephrol. 2017;28(5):1631-1641.
  2. Ortiz A, et al. Mol Genet Metab. 2018;123(4):416-427.
  3. Desnick RJ, et al. Ann Intern Med. 2003;138(4):338-346.
  4. Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30.
  5. Arends M, et al. J Inherit Metab Dis. 2018;41(1):141-149.
  6. Martins, AM, et al. The Journal of pediatrics. 2009;155(4): S19-S31.