Diagnosing Fabry Disease

Although symptoms generally appear in childhood, they may go unrecognized until adulthood when organ system damage has already occurred.1 Early diagnosis is of particular importance with Fabry disease, since the disease is progressive and can be life-threatening.

Patients with a known familial history of Fabry disease should be tested by a confirmatory method regardless of symptomology.

Presumptive clinical diagnosis

A presumptive diagnosis of Fabry disease can be made on the basis of signs and symptoms, including the characteristic angiokeratomas and corneal whorling (visible through slit lamp ophthalmoscopy). Further support comes from taking a family history, noting other family members with symptoms such as early renal disease, early stroke, and early cardiac problems.

Signs and symptoms you are most likely to see in your specialty 

Definitive diagnosis

Definitive diagnosis can be made in males by testing for deficient α-galactosidase A (α-GAL) enzyme activity in plasma, leukocytes, cultured skin fibroblasts, biopsied tissue, or dried blood.2

After a diagnosis is made, patients should be carefully assessed for evidence of renal, cardiac, or neurologic involvement.

More on treating Fabry disease symptoms 

Diagnosis in women

Because females with Fabry disease can have α-GAL activity in the low-normal range, mutation or linkage analysis should be used.3 In families with an identified mutation, mutation analysis is the definitive way to identify females. In families for whom a specific mutation is not documented, linkage analysis can be performed.3 More than 400 gene mutations for Fabry disease have been identified; none of them, however, are common.4

Although females with the altered gene may be asymptomatic or present with mild clinical manifestations, definitive identification of heterozygotes is important. Diagnosis allows practitioners to monitor for new or worsening symptoms, and can help with identifying other family members with the disease.

Affected females can be diagnosed with Fabry disease by very low or absent α-galactosidase A (α-GAL) activity and by lipid disposition in biopsied tissues or urinary sediment. Many female carriers (with or without symptoms) have below-normal levels of α-GAL activity and/or characteristic corneal opacities.

More about Fabry disease in women 

Differential diagnosis

Fabry disease should be considered in the differential diagnosis of fever, pain, and skin lesions of unknown origin, or in stroke or renal disease of unknown etiology. Additionally, symptoms in Fabry disease are similar to those of other disorders, including:

  • Rheumatoid or juvenile arthritis
  • Rheumatic fever
  • Erythromelalgia
  • Lupus
  • “Growing pains”
  • Petechiae
  • Raynaud’s syndrome
  • Multiple sclerosis

Misleading signs and symptoms

Many of the common signs and symptoms are similar to other, more common conditions which can make Fabry disease difficult to diagnose. The table below summarizes the more common differential diagnoses as well as the shared manifestations that may be suggestive of that particular disease.

Fabry disease symptom: May be diagnosed as:
Abdominal pain (severe) Acute appendicitis
Acute pain in extremities Erythromelagia, "growing pains"
Acute pain with no apparent cause Neurosis
Angiokeratomas Lupus, petechiae
Elevated erythrocyte sedimentation rate Juvenile or rheumatoid arthritis
Fatigue Chronic fatigue syndrome, lupus
Joint pain Juvenile or rheumatoid arthritis
Pain and temperature sensitivity in extremities Raynaud's syndrome
Stroke-like events in brainstem structures Multiple sclerosis

Identifying family members at risk

A genetic counselor should be enlisted to assist in developing a family pedigree to identify other family members with Fabry disease, and in directing families to diagnostic, medical, and support services.


1. Shelley ED, WB Shelley, TW Kurczynski. Painful fingers, heat intolerance, and telangiectases of the ear: easily ignored childhood signs of Fabry disease. Pediatr Dermatol. 1995;12:215-219.

2. Desnick RJ, YA Ioannou, CM Eng. α-galactosidase A deficiency: Fabry disease. In: The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill, 2001: 3733-3774.

3. Caggana M, GA Ashley, RJ Desnick, CM Eng. Fabry disease: molecular carrier detection and prenatal diagnosis by analysis of closely linked polymorphisms at Xq22.1. Am J Med Genet. 1997;71:329-335.

4. The Human Gene Mutation Database. www.hgmd.org. Accessed January 3, 2018.