What You Need to Know About Fabry Disease

Amanda Balbi
Senior Managing Editor, Consultant360

Balbi A. What you need to know about Fabry disease. Consultant360. Published online August 4, 2021.


Fabry disease is a rare genetic disorder, estimated to affect 3800 men and 7600 women in the United States.1 The disease is caused by a deficiency of the α-galactosidase A enzyme on the GLA gene, which is located on the X chromosome.2 Because Fabry disease is an X-linked genetic disorder, it affects men more than women.2 All ethnicities are affected equally, although prevalence varies by geographic region.2

The 2 major disease phenotypes are classic type 1 and later-onset type 2.1,2 Classic type 1 typically presents in childhood or adolescence, whereas type 2 presents in adults when the disease has progressed to include heart, renal, and/or vascular disease. Because the differential diagnosis is broad, Fabry disease often goes undiagnosed or the diagnosis is delayed.3,4 However, Fabry disease is treatable with enzyme replacement therapy.4

Screening and Diagnosis

The first steps for diagnosing Fabry disease include taking a detailed history, conducting a thorough physical examination, and conducting genetic testing to evaluate α-galactosidase A enzymes and the specific GLA mutation. For male patients with classic type 1 Fabry disease, symptoms will likely appear in childhood or adolescence and can include:2,4

  • Acroparesthesias
  • Anhidrosis or hypohidrosis
  • Angiokeratomas
  • Gastrointestinal issues
  • Corneal dystrophy
  • Chronic fatigue
  • Dizziness
  • Headache
  • Generalized weakness
  • Nausea and/or vomiting
  • Delayed puberty
  • Lack of or sparse hair growth
  • Rarely malformation of the finger joints


For men with late-onset type 2 Fabry disease, symptoms may not appear until the disease progresses, at which time renal insufficiency and/or cardiac or cerebrovascular disease are present.2 Other common comorbidities include:2,4

  • Respiratory anomalies like interstitial lung disease
  • Hearing loss or tinnitus
  • Dizziness and vertigo
  • Auditory neuropathy


Patients who have cardiac involvement should undergo imaging studies as soon as possible.5 Transthoracic echocardiography scanning can assess cardiomyopathy and ventricular function, as left ventricular hypertrophy and a prominent papillary muscle are common in Fabry disease.5 To assess renal function, baseline serum creatinine, urine protein, and glomerular filtration rate should be evaluated.5 For patients with a history of or physical examination significant for neurological signs, a magnetic resonance imaging scan of the brain or audiometry screen should be conducted.5

For female patients, symptoms can vary from asymptomatic to as severe as male patients with classic type 1 disease.2 Recent research has suggested that late-onset type 2 disease in women is less frequent and severe than in men.2 Presenting signs and symptoms are similar between the sexes, but women with later-onset type 2 disease are less likely to have corneal findings than women with classic type 1 disease.2


After a diagnosis is made, it is important to create a treatment plan and regimen. Earlier treatment can reduce the burden of end-organ failure in later life. The current consensus for treating Fabry disease were published in 2019.4 The recommendations include 2 forms of enzyme replacement therapy: agalsidase α and agalsidase β. Both treatments should be administered intravenously every other week for the lifetime of the patient. Agalsidase α, 0.2 mg/kg, is indicated for patients aged 7 years or older, and agalsidase β, 1.0 mg/kg, is indicated for those aged 8 years or older.4

In addition to treating Fabry disease, treatment of comorbid heart, renal, or vascular disease is also important. Counseling patients on healthy dietary and lifestyle changes is the first step. If dyslipidemia is present, treatment with statins is indicated. If the albumin level is above 19.9 g/dL, renal involvement is likely and enzyme replacement therapy is indicated.4

For acute pain management, the consensus is prescribing analgesics for children, as well as counseling them on avoiding triggers such as heat or exercise. For adults, neuropathic pain should be treated with antiepileptic medications, tricyclic antidepressant medications, and serotonin-norepinephrine update inhibitors.4

Gene therapy may also be a treatment option in the future, but more research is needed.6


In summary, Fabry disease is often a missed diagnosis, which leads to a delay in treatment. If treatment is delayed into adulthood, organ involvement is highly likely. The current consensus document outlines diagnosis criteria and treatment options for clinicians, but more evidence-based guidelines are needed.


1. How common is Fabry disease? Frequently Asked Questions. National Fabry Disease Foundation. Accessed August 4, 2021.

2. Fabry Disease. Rare Disease Database. National Organization for Rare Disorders. Updated 2019. Accessed August 4, 2021.

3. Hoffmann B, Mayatepek E. Fabry disease-often seen, rarely diagnosed. Dtsch Arztebl Int. 2009;106(26):440-447.

4. Germain DP, Fouilhoux A, Decramer S, et al. Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients. Clin Genet. 2019;96(2):107-117.

5. Vardarli I, Rischpler C, Herrmann K, Weidemann F. Diagnosis and screening of patients with Fabry disease. Ther Clin Risk Manag. 2020;16:551-558.

6. Domm JM, Wootton SK, Medin JA, West ML. Gene therapy for Fabry disease: progress, challenges, and outlooks on gene-editing. Mol Genet Metab. Published online July 21, 2021.